Τρίτη, 31 Ιουλίου 2018

Effect of passive heat exposure on cardiac autonomic function in healthy children

Abstract

Purpose

The aim of this study was to examine the effect of passive heat stress on heart rate variability parameters in healthy children.

Method

Fifteen children (9.3 ± 1.6 years) of both sexes (eight male) participated in two randomized experimental conditions separated by 5–12 days. Children were seated for 2 h in an environmental chamber for two sessions: neutral (22.4 ± 0.1 °C, 40.4 ± 6.5% RH) and hot (34.9 ± 0.3 °C, 36.6 ± 6.2% RH) conditions. Electrocardiogram, mean skin temperature, tympanic temperature, and blood pressure were recorded. Five min epochs were averaged for analysis of cardiac autonomic function over the 2-h protocol.

Result

Mean skin and tympanic temperatures and heart rate increased during the hot condition (all p < 0.01) while mean arterial pressure decreased (p < 0.01). During the hot condition, root-mean-square difference of successive normal RR intervals (45 ± 9 to 38 ± 7 ms), and low- (LF, 1536 ± 464 vs. 935 ± 154 ms2) and high-frequency power (HF, 1544 ± 693 vs. 866 ± 355 ms2) decreased, whereas LF/HF ratio increased (1.64 ± 0.24 vs. 2.40 ± 0.23 au); all indices were different from neutral (all p < 0.05). These were all unchanged throughout the neutral condition (all p > 0.05), except for LF/HF ratio which decreased during the neutral condition (p < 0.05).

Conclusion

Mild hyperthermia elicited marked changes in cardiac autonomic control in young children. These data suggest that, in healthy children, vagal withdrawal is responsible for the cardiac autonomic response to hyperthermia.



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Colitis and Pancreatitis in a Patient with Systemic Lupus Erythematosus: Due to Disease or to Drug?



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Computer vision for total laparoscopic hysterectomy

Asian Journal of Endoscopic Surgery, EarlyView.


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A Randomized, Controlled Pilot Study of a Manualized Intervention for Caregivers of Patients with Traumatic Brain Injury in Inpatient Rehabilitation

Publication date: Available online 31 July 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Janet P. Niemeier, Jeffrey S. Kreutzer, Jennifer H. Marwitz, Adam P. Sima

Abstract
Objective

Investigate effectiveness of a 5-session manualized intervention for addressing needs of caregivers of persons in acute traumatic brain injury (TBI) rehabilitation.

Design

Prospective, pilot randomized controlled trial

Setting

Inpatient brain injury rehabilitation unit, level 1 trauma center

Participants

N = 93 patients with moderate to severe TBI and their family members were enrolled in the study with 42 randomized to the treatment group, 51 to the control group.

Intervention

Five-session, manualized caregiver intervention with educational, stress and anxiety self-management, coping, and emotional support components.

Main Outcome Measures

Family Needs Questionnaire-R (FNQ-R), Knowledge Assessment, Zarit Family Burden Scale, and Brief Symptom Inventory-18 were collected at pre-treatment, post-treatment, and 3-month follow-up.

Results

Treatment group caregivers showed an increase in met needs for Emotional, Instrumental and Professional Support, and brain injury knowledge from baseline to post-treatment whereas controls did not. Between group differences were significant for only Emotional Support needs. Treatment effects were not sustained at 3-month follow-up.

Conclusions

Caregivers of persons undergoing acute TBI rehabilitation may benefit from interventions that target their unique needs. Caregivers may require additional and longer-term supports to sustain treatment benefits.



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Understanding health-related quality of life of caregivers of civilians and service members/veterans with Traumatic Brain Injury: Establishing the reliability and validity of PROMIS social health measures

Publication date: Available online 31 July 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Noelle E. Carlozzi, Phillip A. Ianni, Rael T. Lange, Tracey A. Brickell, Michael A. Kallen, Elizabeth A. Hahn, Louis M. French, David Cella, Jennifer A. Miner, David S. Tulsky

Objective

To examine the reliability and validity of the short form (SF) and computer adaptive test (CAT) versions of the Patient Reported Outcomes Measurement Information System (PROMIS) measures of social health of caregivers of civilians and service members/veterans (SMVs) with traumatic brain injury (TBI).

Design

Self-report questionnaires administered through an on-line data collection platform.

Setting

Hospital and community-based outreach at three TBI Model Systems rehabilitation hospitals, an academic medical center, and a military medical treatment facility

Participants

560 (344 civilians and 216 military) caregivers of individuals with a documented TBI

Intervention

N/A

Main Outcome Measures

5 PROMIS Social Health Measures

Results

All five PROMIS social health measures exceeded the a priori criterion for internal consistency reliability (≥ 0.70); most PROMIS measures met the criterion for test-retest reliability (≥ 0.70) in the civilian sample; in the SMV sample, test-retest reliability was generally below this criterion, except for Social Isolation. For both samples, convergent validity was supported by moderate correlations between the 5 PROMIS social health measures and related measures, and discriminant validity was supported by low correlations between PROMIS social health measures and measures of dissimilar constructs. Most PROMIS scores indicated significantly worse social health in both samples of those caring for individuals who were low functioning. Finally, impairment rates in social health were elevated for those caring for low functioning individuals, especially in the SMV sample.

Conclusions

The PROMIS computer adaptive test and short form social health measures have potential clinical utility for use in caregivers of civilians and SMVs with TBI.



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The development of a new computer adaptive test to evaluate feelings of being trapped in caregivers of individuals with traumatic brain injury: TBI-CareQOL Feeling Trapped Item Bank

Publication date: Available online 31 July 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Noelle E. Carlozzi, Michael A. Kallen, Robin Hanks, Anna L. Kratz, Elizabeth A. Hahn, Tracey A. Brickell, Rael T. Lange, Louis M. French, Phillip A. Ianni, Jennifer A. Miner, Angelle M. Sander

Abstract
Objective

To develop a new patient-reported outcome measure that captures feelings of being trapped that are commonly experienced by caregivers of individuals with traumatic brain injury (TBI).

Design

Cross-sectional

Setting

Three TBI Model Systems rehabilitation hospitals, an academic medical center, and a military medical treatment facility.

Participants

Caregivers of civilians with TBI (n=344) and caregivers of service members/veterans with TBI (n=216).

Interventions

Not applicable.

Outcome Measures

TBI-CareQOL Feeling Trapped Item Bank

Results

From an initial item pool of 28 items, exploratory and confirmatory factor analyses supported the retention of 16 items. After graded response model (GRM) and differential item functioning (DIF) analyses were conducted, 15 items were retained in the final measure. GRM calibration data, along with clinical expert input, was used to choose a 6-item, static short form, and the calibration data was utilized for programming of the TBI-CareQOL Feeling Trapped computer adaptive test (CAT). CAT simulation analyses produced an r = 0.99 correlation between CAT scores and the full item-bank. Three-week short form test-retest reliability was very good (r = 0.84).

Conclusions

The new TBI-CareQOL Feeling Trapped item bank was developed to provide a sensitive and efficient examination of the impact that feelings of being trapped, due to the caregiver role, have on health-related quality of life (HRQOL) for caregivers of individuals with TBI. Both the CAT and corresponding 6-item short form demonstrate excellent psychometric properties. Future work is needed to establish the responsiveness of this measure to clinical interventions for these caregivers.



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Parallel Genomic Engineering of Two Drosophila Genes Using Orthogonal attB/attP Sites

Precise modification of sequences in the Drosophila melanogaster genome underlies the powerful capacity to study molecular structure-function relationships in this model species. The emergence of CRISPR/Cas9 tools in combination with recombinase systems such as the bacteriophage serine integrase C31 has rendered Drosophila mutagenesis a straightforward enterprise for deleting, inserting and modifying genetic elements to study their functional relevance. However, while combined modifications of non-linked genetic elements can be easily constructed with these tools and classical genetics, the independent manipulation of linked genes through the established C31-mediated transgenesis pipeline has not been feasible due to the limitation to one attB/attP site pair. Here we extend the repertoire of C31 transgenesis by introducing a second pair of attB/attP targeting and transgenesis vectors that operate in parallel and independently of existing tools. We show that two syntenic orthologous genes, CG11318 and CG15556, located within a 25 kb region can be genomically engineered to harbour attPTT and attPCC sites. These landing pads can then independently receive transgenes through C31-assisted integration and facilitate the manipulation and analysis of either gene in the same animal. These results expand the repertoire of site-specific genomic engineering in Drosophila whilst retaining the well established advantages and utility of the C31 transgenesis system.



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H&H Medical Corporation launches Safe and Sound Schools fundraising initiative

H&H Medical Corporation, provider of high-quality products for emergency first responders, today kicked off its fundraising campaign to support Safe and Sound Schools. From July 1 through September 31, 2018, H&H Medical Corporation will donate a portion of revenue from online sales of select trauma kits and supplies to Safe and Sound Schools to help fund free programs and resources for...

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Improving internal model strength and performance of prosthetic hands using augmented feedback

The loss of an arm presents a substantial challenge for upper limb amputees when performing activities of daily living. Myoelectric prosthetic devices partially replace lost hand functions; however, lack of se...

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Using principal component analysis to reduce complex datasets produced by robotic technology in healthy participants

The KINARM robot produces a granular dataset of participant performance metrics associated with proprioceptive, motor, visuospatial, and executive function. This comprehensive battery includes several behavior...

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Laparoscopic distal pancreatectomy: which factors are related to open conversion? Lessons learned from 68 consecutive procedures in a high-volume pancreatic center

Abstract

Background

Laparoscopic distal pancreatectomy represents a difficult surgical procedure with an high conversion rate to open procedure. The factors related to its difficulty and conversion to open distal pancreatectomy were rarely reported. The aim of the present study was to identify which factors are related to conversion from laparoscopic to open distal pancreatectomy.

Methods

A retrospective study of a prospective database of 68 patients who underwent laparoscopic distal pancreatectomy was conducted at a high-volume center by pancreatic surgeons experienced with laparoscopic surgery. Pre-intra and postoperative data were collected. Patients who completed a laparoscopic distal pancreatectomy were compared with those who needed a conversion to the open approach as regard demographic, clinical, radiological, and surgical data. Univariate and multivariate analyses were carried out.

Results

Univariate analysis suggested that the site of the lesion, the extension of pancreatic resection, and the requirement for an extended procedure to adjacent organs were significantly associated with the risk of conversion to the open approach. Multivariate analysis showed that only the extension of the pancreatic resection (subtotal pancreatectomy) was significantly related to the odds of conversion [odds ratio (OR) 19.5; 95% confidence interval (CI) 1.1–32.3; P = 0.038]. Preoperative suspicion of malignancy differed between the two groups; however, this difference did not reach statistical significance (P = 0.078).

Conclusions

Despite the limitations of the study, only the extension of pancreatic resection seemed to be the main factor related to conversion during laparoscopic distal pancreatectomy.



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A prospective randomized trial of EUS-guided tissue acquisition using a 25-gauge core biopsy needle with and without a stylet

Abstract

Background

Endoscopic ultrasound (EUS)-guided tissue acquisition has become the most effective method of obtaining specimens from a solid lesion adjacent to the gastrointestinal tract. No data exist regarding the use of a stylet in the core biopsy needle during EUS-guided tissue acquisition. The aims of this study were to evaluate the feasibility, safety, and diagnostic yield of a 25-gauge core biopsy needle without (S−) a stylet and to compare its performance with that of a 25-gauge core biopsy needle with (S+) a stylet in patients with solid lesions adjacent to the gastrointestinal tract.

Methods

From November 2013 to January 2016, we performed 114 EUS-guided tissue acquisitions for the diagnosis of solid lesions adjacent to the gastrointestinal tract in a randomized controlled trial. Patients were randomly assigned to the S+ group (n = 57) or the S− group (n = 57). EUS-guided tissue acquisition was performed using a 25-gauge core biopsy needle without an on-site cytopathologist.

Results

There were no significant differences in technical success (100 vs. 100%, p = 1.000), the mean number of needle passes (7.0 ± 1.6 vs. 6.8 ± 1.5, p = 0.556), needle malfunction (0 vs. 1.8%, p = 1.000), or complications (1.8 vs. 0%, p = 1.000) between the S+ and S− groups. Both groups exhibited comparable outcomes with respect to cytological diagnostic accuracy (93.0 vs. 91.2%, p = 1.000) and histological diagnostic accuracy (86.0 vs. 87.7%, p = 1.000) for malignancy. The procedure time was significantly shorter in the S− group than in the S+ group (32.4 ± 11.7 vs. 39.7 ± 8.6 min, p < 0.001).

Conclusions

EUS-guided tissue acquisition using a 25-gauge core biopsy needle without a stylet did not decrease the diagnostic yield for malignancy and was associated with a shorter procedure time than that associated with a stylet.



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Clinical outcomes of minimally invasive treatment for early gastric cancer in patients beyond the indications of endoscopic submucosal dissection

Abstract

Background

Endoscopic submucosal dissection (ESD) with laparoscopic sentinel lymph node dissection (ESN) and endoscopic full-thickness gastric resection with laparoscopic sentinel lymph node dissection (Hybrid-natural orifice transluminal endoscopic surgery, Hybrid-NOTES) are minimally invasive treatment options for early gastric cancer (EGC) beyond the indications of ESD. This study aimed to evaluate the short- and long-term clinical outcomes of ESN and Hybrid-NOTES.

Methods

We retrospectively analyzed patients who had undergone ESN or Hybrid-NOTES for EGC from January 2009 to March 2013. A total of 48 patients, including 21 undergoing ESN and 27 undergoing Hybrid-NOTES, were enrolled. All patients had cancer stage T1N0M0, EGC less than 5 cm in size, and suspected submucosal invasion according to imaging or biopsy-proven diffuse-type histology.

Results

In ESN and Hybrid-NOTES, the curative resection rates were 76.5% and 90.9% of patients, respectively. In the ESN group, 5 patients underwent an additional gastrectomy (1 for lymph node metastasis (LNM), 3 for surgical complications, and 1 for noncurative resection). In the Hybrid-NOTES group, 6 patients underwent additional gastrectomy, (1 for LNM, 3 for surgical complications, and 2 for noncurative resection). Of the 37 patients who were followed up in the long-term (a median follow-up of 59.8 months), one was found to have liver metastasis after ESN and received palliative chemotherapy.

Conclusions

ESN and Hybrid-NOTES have shown favorable long-term outcomes despite their technical limitations. These methods may be utilized as a bridge between ESD and gastrectomy in cases of EGC with a high risk of LNM beyond the ESD indications.



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Approaching the superior mesenteric artery from the right side using the proximal-dorsal jejunal vein preisolation method during laparoscopic pancreaticoduodenectomy

Abstract

Background

Although the artery-first approach is widely used in open pancreaticoduodenectomy, it is difficult to laparoscopically expose the origin of the inferior pancreaticoduodenal artery (IPDA) from the left side of the superior mesenteric artery (SMA). By contrast, damaging the inferior pancreaticoduodenal veins (IPDVs) is possible when approaching the IPDA from the right side of the SMA. To facilitate the artery-first approach in laparoscopic pancreaticoduodenectomy (LPD), we focused on the proximal-dorsal jejunal vein (PDJV) that branched from the superior mesenteric vein (SMV) dorsal side and drained the IPDVs. This study aimed to clarify the usefulness of the right SMA approach using the PDJV preisolation method.

Methods

The PDJV was first isolated, and the IPDVs were divided along the PDJV on the right side of the SMA. Then, the IPDA was divided at the root without first separating the pancreatic head from the portal vein and the SMV. Overall, 21 patients underwent this approach, and the results were retrospectively compared with those of 21 patients who underwent the artery-first approach, which was performed on the left side of the SMA. Anatomical characteristics of the PDJV were evaluated using multidetector computed tomography for the two groups.

Results

Operative times and resection times were significantly lower for the PDJV preisolation group than for the conventional LPD group (489.3 vs. 541.7 min, respectively; p = 0.002). During anatomical evaluation, 41 patients (97.6%) had a PDJV that drained from the SMV dorsally and was in contact with the anterior aspect of the uncinate process. The PDJV was confirmed as the first jejunal vein in 31 patients (73.8%) and as the second jejunal vein in 10 patients (23.8%).

Conclusions

This approach facilitates dissection of the IPDA on the right side of the SMA, thereby reducing operative times.



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S093: pneumatic balloon dilation for palliation of recurrent symptoms of achalasia after esophagomyotomy

Abstract

Background

Achalasia is a chronic disease affecting the myenteric plexus of the esophagus and lower esophageal sphincter. Treatment is aimed at palliating symptoms to improve quality of life. Treatment options for symptom relapse after esophagomyotomy include botox injection, repeat myotomy, per-oral endoscopic myotomy, or pneumatic balloon dilation (PBD). Data demonstrating the safety and efficacy of PBD for recurrence are scarce. With a lack of published data, guidelines have suggested avoiding PBD for recurrent achalasia because of concern for a high risk of perforation.

Methods

A retrospective review of patients who underwent PBD for recurrent symptoms of achalasia after esophagomyotomy between 2007 and 2017 was conducted. PBD was performed at 30 mm and held for 60 s under fluoroscopic guidance. Patients with residual symptoms had subsequent dilations at increasing 5 mm increments to a maximum of 40 mm. Patient demographics, Eckardt scores, presence of hiatal hernia, time from myotomy to recurrence, and diagnostic modalities were reported. The primary outcome was need for further endoscopic or surgical intervention. Complications are reported as secondary outcomes.

Results

One-hundred eight esophagomyotomies were done during the study period. Fourteen patients underwent PBD for recurrent symptoms. The median time to symptom recurrence after esophagomyotomy was 28 months. The median Eckardt score was 6. Ten of 14 patients had an intervention between the initial surgery and PBD (9 standard dilations and 1 botox injection). A total of 23 PBD were done. Seven patients required dilation at 35 mm and two patients required dilation at 40 mm. Eleven patients required no further intervention at a median follow-up of 27.7 months. There were three treatment failures: one required repeat esophagomyotomy and two had no further treatments. There were no periprocedural complications.

Conclusion

Serial PBD is safe and effective in treatment of recurrent symptoms of achalasia after esophagomyotomy.



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Acute cholecystitis: comparing clinical outcomes with TG13 severity and intended laparoscopic versus open cholecystectomy in difficult operative cases

Abstract

Introduction

The revised Tokyo Guidelines include criteria for determining the severity of acute cholecystitis with treatment algorithms based on severity. The aim of this study was to investigate the relationship of the revised Tokyo Guidelines severity grade to clinical outcomes of cholecystectomy for acute cholecystitis.

Methods

We identified 66 patients with acute cholecystitis from a prior study of difficult cholecystectomy cases. We examined the relationship between severity grade and multiple variables related to perioperative and postoperative outcomes.

Results

A more severe revised Tokyo Guidelines grade was associated with a higher number of complications (p = 0.03) and a higher severity of complications (p = 0.01). Severity grade did not predict operative time, estimated blood loss, intensive care unit admission or length of stay. Compared to planned open cholecystectomy, intended laparoscopic cholecystectomy was associated with significantly fewer total and Clavien–Dindo grade 3 complications, fewer intensive care unit admissions, and shorter length of stay (p values range from 0.03 to < 0.0001).

Conclusion

In technically difficult operations for acute cholecystitis, the revised Tokyo guidelines severity grade correlates with the number and severity of complications. However, intended performance of laparoscopic cholecystectomy rather than open cholecystectomy in difficult operations predicts broader beneficial outcomes than severity grade.



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Oncological and surgical result of hepatoma after robot surgery

Abstract

Background

Most liver resections are currently performed using an open approach. Robotic hepatectomy has been suggested as a safe and effective approach for hepatocellular carcinoma; however, studies regarding oncological and surgical outcomes are still limited. Accordingly, we performed this study to compare the surgical and oncological outcomes between robotic and open approaches.

Methods

Between June, 2013 and July, 2016, a total of 63 HCC patients undergoing robotic hepatectomy, and 177 patients undergoing open hepatectomy were included in this study to assess the surgical and oncological outcomes after hepatectomy. The data of demographic, clinical features, hepatitis profile, tumor characters, TNM stage, surgical type, pathological outcomes, and postoperative results were collected prospectively and analyzed retrospectively.

Results

The demographic and clinical features of patients with HCC in both groups were statistically comparable. The robotic group had longer operative times (296 ± 84 vs. 182 ± 51 min, p = 0.032). The postoperative complications rate was slightly lower in the robotic group (11.1 vs. 15.3%, p = 0.418). The rate of Ro resection was similar in both groups (93.7 vs. 96%, p = 0.56). The length of hospital stay was significantly shorter in the robotic group (6.21 ± 2.06 vs. 8.18 ± 6.99 days, p = 0.001). The overall recurrence rate of HCC was lower in the robotic group (27 vs. 37.3%, p = 0.140). The 1, 2, 3 year disease-free survival rates were 72.5, 64.3, and 61.6%, respectively, for the open group, while they were 77.8, 71.9, and 71.9%, respectively, for the robotic group, (p = 0.325). The 1, 2, 3 year overall survival rates were 95.4, 92.3, and 92.3%, respectively, for the open group, while they were 100, 97.7, and 97.7%, respectively, for the robotic group (p = 0.137).

Conclusion

Robotic surgery is a safe and feasible procedure for liver resection in selected patients. The oncological and surgical outcomes of robotic hepatectomy were comparable to open surgery. The robotic hepatectomy carried significantly shorter length of hospital stay.



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Robotic-assisted laparoscopic median arcuate ligament release: 7-year experience from a single tertiary care center

Abstract

Background

Despite previous reports of robotic-assisted laparoscopic release for median arcuate ligament syndrome (MALS), the safety and efficacy profile of this approach has been difficult to establish due to the rarity of this diagnostic entity. We aim to present our experience from a tertiary minimally invasive surgery referral center.

Methods

A case series was performed whereby all patients who underwent robotic-assisted MAL release from July 2010 to July 2017 at our institution were included. Diagnosis of MALS was made based on consideration of symptom presentation, celiac artery duplex ultrasound, and corresponding findings on Computed Tomography (CT) or Magnetic Resonance Angiography (MRA). Outcomes up until the most recent clinic follow-up were reviewed.

Results

A total of 13 patients underwent robotic-assisted MAL release. Patients' age ranged from 16 to 71 years (mean 38 years) and consisted primarily of females (76.9%). Most common presenting symptoms included postprandial pain (76.9%), weight loss (76.9%), nausea and vomiting (76.9%). Mean symptom duration was 3 years (range 1–10 years). No intraoperative complications. None required conversion to open surgery. One case required a conversion back to laparoscopy due to anatomical complexity. The mean operative time for successfully completed robotic cases was 94.6 min (range 52–120 min), and for all cases including converted case was 103.5 min (52–210 min). Mean follow-up duration was 19.7 months (range 1–77 months). During subsequent follow-up, a 30-day readmission rate of 23.1% was observed. All but one of the patients experienced prompt symptom improvement. Four patients had symptom recurrence during follow-up.

Conclusions

Our experience demonstrates that the robotic-assisted approach to MAL release may be safe and efficacious in selected patients. Prospective comparative studies are required to further evaluate its outcomes against conventional laparoscopic approach, the current gold standard.



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Endoscopy versus radiology in post-procedural monitoring after peroral endoscopic myotomy (POEM)

Abstract

Background

The newly developed technique of peroral endoscopic myotomy (POEM) has been shown to be effective in several short- and mid-term studies. Limited information is available about the adequacy of immediate post-POEM monitoring tests.

Methods

POEM was performed under general anesthesia in 228 patients (59.6% male, mean age 45.6 ± 15.5 years). Post-procedural checks comprised clinical and laboratory examination, and, during post-procedure days 1–5, endoscopy and—in the first 114 cases—radiologic examination using water-soluble contrast (1st group); the remaining patients underwent post-procedure controls without radiology (2nd group). Main outcome was value of endoscopic compared to radiologic control for recognition of early adverse events.

Results

In the first group, routine fluoroscopic contrast swallow suggested minor leakages at the mucosal entry site in two cases which was confirmed endoscopically in only one. Endoscopy revealed two minor entry site leakages and, in six additional cases, dislocated clips without leakage (overall 5.3%). All eight patients underwent reclipping and healed without clinical sequelae. In the 2nd group, endoscopy showed 5 clip dislocations (all reclipped) and one ischemic cardiac perforation in a patient with clinical deterioration on post-POEM day 1 who had to undergo surgery after confirmation of leakage by CT.

Conclusions

Radiologic monitoring (contrast swallow) after POEM is not useful and can be omitted. Even routine endoscopic monitoring for detection and closure of minor defects of the mucosal entry site yields limited information with regards to final outcome; major complications are very rare and probably associated with clinical deterioration.

Clinical Trials Gov Registration number of the main study: NCT01405417.



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Correction to: Pheochromocytoma diagnosed during pregnancy: lessons learned from a series of ten patients

The original article was updated to correct the listing of A. Hamy's name; it is correct as displayed above.



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EAES classification of intraoperative adverse events in laparoscopic surgery

Abstract

Background

Surgical outcomes are traditionally evaluated by post-operative data such as histopathology and morbidity. Although these outcomes are reported using accepted systems, their ability to influence operative performance is limited by their retrospective application. Interest in direct measurement of intraoperative events is growing but no available systems applicable to routine practice exist. We aimed to develop a structured, practical method to report intraoperative adverse events enacted during minimal access surgical procedures.

Methods

A structured mixed methodology approach was adopted. Current intraoperative adverse event reporting practices and desirable system characteristics were sought through a survey of the EAES executive. The observational clinical human reliability analysis method was applied to a series of laparoscopic total mesorectal excision (TME) case videos to identify intraoperative adverse events. In keeping with survey results, observed events were further categorised into non-consequential and consequential, which were further subdivided into four levels based upon the principle of therapy required to correct the event. A second survey phase explored usability, acceptability, face and content validity of the novel classification.

Results

217 h of TME surgery were analysed to develop and continually refine the five-point hierarchical structure. 34 EAES expert surgeons (69%) responded. The lack of an accepted system was the main barrier to routine reporting. Simplicity, reproducibility and clinical utility were identified as essential requirements. The observed distribution of intraoperative adverse events was 60.1% grade I (non-consequential), 37.1% grade II (minor corrective action), 2.4% grade III (major correction or change in post-operative care) and 0.1% grade IV (life threatening). 84% agreed with the proposed classification (Likert scale 4.04) and 92% felt it was applicable to their practice and incorporated all desirable characteristics.

Conclusion

A clinically applicable intraoperative adverse event classification, which is acceptable to expert surgeons, is reported and complements the objective assessment of minimal access surgical performance.



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Defining minimal clearances for adequate lymphatic resection relevant to right colectomy for cancer: a post-mortem study

Abstract

Background

There has been a lengthy discussion on the extent of lymphatic resection for right-sided colon cancer and the central borders of the mesentery that are not yet defined. The objectives of this study are to define minimal clearances for adequate lymphatic resection in regard to colic artery origins and the superior mesenteric artery (SMA) and vein (SMV) relevant to right colectomy.

Methods

Central mesenteric lymph vessels, nodes, and blood vessels were dissected in 16 cadavers. Cranial–caudal clearances were defined as distances between an individual colic artery origin (ileocolic, right colic, and median colic artery) and the outermost lymphatic vessel within its lymphovascular bundle, cranial and caudal along the SMA. Long lymphatic vessels crossing the SMV between arterial bundles were counted and they constituted the medial clearances. An arbitrary watershed between small bowel and colonic lymph was localized. Immunohistochemistry was performed to histologically verify lymphatic vessels.

Results

Cranial–caudal clearances were ileocolic 3.6 ± 1.9 and 5.7 ± 1.9; right colic 2.8 ± 1.6 and 3.3 ± 1.0; middle colic artery bundle 6.3 ± 2.7 and 5.9 ± 2.4 mm, respectively. Long lymphatic vessels crossing the SMV between arterial buntles and approaching the SMA were found in all cadavers (antero/posteriorly in 12, only anteriorly in 4), median 3.5 (1–7) long lymphatic vessels anteriorly, and 1.5 (0–5) posteriorly per cadaver.

Conclusions

Right colonic lymphovascular bundles are volumes of mesenteric tissue that surround the superior mesenteric vessels anteriorly and posteriorly. Long lymphatic vessels traverse the superior mesenteric vein anteriorly/posteriorly approaching the superior mesenteric artery between arterial bundles and placing the medial clearance on the left side of the artery. These do not correlate to arterial crossing patterns. Cranial–caudal clearances determine the tissue to be removed superior/inferior to arterial origins together with long lymphatic vessels transversing independently between the lymphovascular bundles placing the weight of lymphatic resection on the mesenteric tissue and not on the level of vessel division (High tie).



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Implementation of mini gastric bypass in the Netherlands: early and midterm results from a high-volume unit

Abstract

Background

Mini gastric bypass (MGB) is a promising and attractive alternative bariatric procedure. In 2011, we introduced MGB in our high-volume bariatric unit. Subsequently, we evaluated short- and midterm results of this procedure.

Methods

A prospective cohort of patients who underwent MGB between 2012 and 2013 was retrospectively evaluated.

Results

From 2012 to 2013, primary MGB was performed in 287 patients with a mean BMI of 42 kg/m2 (range 32–76 kg/m2). The mean operation time was 50 min (range 25–120 min). The mortality rate was 0%. Serious complications, such as leakage, pulmonary embolism, or bleeding, occurred in 3.1% of patients; anastomotic leaks occurred in 1.4% of patients. Conversion to Roux-en-Y gastric bypass for biliary reflux or other indications occurred in six patients (2%). During our initial learning phase, biliary reflux rates were higher due to an overly short pouch. Surgical revision for malnutrition was performed in one patient. Percent excess weight loss and percent total body weight loss were 85 and 35%, respectively, after 1 year; 88 and 36.6%, respectively, after 2 years; and 83 and 34.3%, respectively, after 3 years. Follow-up rates after 1, 2, and 3 years were 96% (277/287), 72% (208/287), and 66% (190/287), respectively.

Conclusions

As a primary bariatric procedure, MGB is associated with good early and midterm results. MGB has the potential to become a significant alternative bariatric procedure. Correct technique is of extreme importance when performing MGB; therefore, the appointment of an experienced MGB surgeon as a guide when beginning to utilize this technique is advised.



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Laparoendoscopic rendezvous in the treatment of cholecysto-choledocholitiasis: a single series of 200 patients

Abstract

Background and aim

Although the ideal management of cholecysto-choledocholitiasis is controversial, the two-stage approach, namely the common bile duct (CBD) clearance through endoscopic retrograde cholangiopancreatography (ERCP) followed by laparoscopic cholecystectomy, remains the standard way of management. However, whenever feasible, the one-stage approach, using the so-called "laparoendoscopic rendezvous" (LERV) technique, offers some advantages, mainly reducing the hospital stay and the risk of post-ERCP pancreatitis. The aim of this study was to evaluate the safety and the efficacy of the one-stage approach, and to compare our results with data from available large studies.

Materials and methods

We reviewed our series of consecutive patients with cholecysto-choledocholitiasis treated by LERV from January 2003, to October 2016. Both elective and emergency cases were included. The primary end-point was the efficacy to obtain the CBD stones clearance. Secondary end-points were morbidity and mortality, operative time, conversion rate, and in-hospital stay.

Results

A total of 200 patients underwent a LERV procedure for the intra-operative diagnosis by intra-operative cholangiogram of cholecysto-choledocholitiasis. In 187 patients (93.5%), it was possible to cannulate the cystic duct with the jag-wire. Success rate was 95%. Conversion rate was 3%. The mean operative time was 135 min and the mean in-hospital stay was 4 days. 29 (14.5%) were the early complications, six mild pancreatitis. Four patients required re-operation during the hospital stay. 11 patients (5.5%) developed late complications during a median follow-up of 57.7 months.

Conclusions

Our results confirm that LERV technique is a safe procedure with high success rates for the treatment of cholecysto-choledocholitiasis. The major advantages include the single-stage treatment, the shorter hospital stay, and the lower incidence of post-ERCP pancreatitis.



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Surgical management of gastroesophageal reflux disease in patients with systemic sclerosis

Abstract

Background

Systemic sclerosis (scleroderma) is frequently associated with both gastroesophageal reflux disease (GERD) and simultaneous esophageal dysmotility. Anti-reflux procedures in this patient population must account for the existing physiology of each patient and likely disease progression. We aim to compare perioperative and intermediate outcomes of fundoplication versus gastric bypass for the treatment of GERD.

Methods

After IRB approval, patients with systemic sclerosis undergoing fundoplication or gastric bypass for the treatment of GERD from 2004 to 2016 were identified. Demographics, perioperative data, immediate complications, and symptom improvement were retrieved and analyzed.

Results

Fourteen patients with systemic sclerosis underwent surgical treatment of GERD during the defined study period. Average body mass index was 26 kg/m2. Seven fundoplications (2 Nissens, 4 Toupets, and 1 Dor) and 7 Roux-en-Y gastric bypasses (RYGB) were performed. No 30-day mortality was observed in either group. Median follow-up was 97 months for the fundoplication group (range 28–204 months), and 19 months for the RYGB group (range 1–164 months). Preoperatively, dysphagia, heartburn, and regurgitation were present in 71% (n = 10), 86% (n = 12), and 64% (n = 9) of patients, respectively. Eleven patients had pH study prior to surgical intervention, and 91% of them had abnormal acid exposure. Esophagitis was evident in 85% (n = 11) of patients during preoperative upper endoscopy, and two patients had Barrett's esophagus. Impaired esophageal motility was present in all RYGB patients and 71% of fundoplication patients. Of the patients who had assessment of their GERD symptoms at follow-up, all five patients in the RYGB group and only 3 (50%) patients in the fundoplication group reported symptom improvement or resolution.

Conclusions

Laparoscopic RYGB as an anti-reflux procedure is safe and may provide an alternative to fundoplication in the treatment of GERD for systemic sclerosis patients with esophageal dysmotility.



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Characteristics of the parathyroid gland in endoscopic thyroidectomy with the application of an image enhancement system

Abstract

Background

To assist surgeons in identifying and preserving the parathyroid gland (PTG) in endoscopic thyroidectomy (ET), we have summarized the characteristics of the PTG and the surrounding tissues in ET by applying the Storz Professional Image Enhancement System (SPIES).

Methods

From November 2014 to May 2016, 182 patients with 613 suspected PTGs were included in our study. The shape, color, area, and density of surface blood vessels (SBVs); whether they were encapsulated with adipose tissue; and whether congestion was present during the operation were summarized. The κ coefficient of interobserver agreement in assessing the area and the density of SBVs of suspected PTGs with and without Spectra A (SA) and Spectra B (SB) modalities were calculated. Multiple binary logistic regression analyses were performed to determine the predictive value of different characteristics for detecting the PTG in ET with the application of SPIES.

Results

With visual identification and histopathological results as reference standards, 291 targeted tissues were identified as PTGs, 256 as adipose tissue, 43 as lymph nodes, and 23 as thyroid tissue. The κ coefficients of interobserver agreement in assessing SBV density with or without the SA and SB modalities were 0.944 ± 0.013 and 0.859 ± 0.021, respectively, and those in assessing SBV area were 0.937 ± 0.014 and 0.841 ± 0.022, respectively. In the comparison between PTGs and other tissues, multiple binary logistic regression analysis revealed that shape, color, SBV density, congestion, and whether tissue was encapsulated with adipose tissue were independent predictive factors of PTGs.

Conclusion

With the application of SPIES, the shape, color, density of SBVs, adipose tissue encapsulation, and congestion were independent factors that predicted PTGs in ET. The SA and SB modalities of SPIES could improve the reliability of SBV density and area classifications in targeted tissues.



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Diagnostic and therapeutic single-operator cholangiopancreatoscopy with SpyGlassDS™: results of a multicenter retrospective cohort study

Abstract

Background and aims

The aim of the study was to evaluate the usefulness and diagnostic and therapeutic outcome of the single-operator cholangiopancreatoscopy (SOC) with SpyGlassDS™.

Methods

In a retrospective multicenter study between November 2015 and January 2017, SpyGlassDS™ procedures were analyzed in participating centers. Indications, accuracy of SOC-guided biopsies, management of large bile duct stones, and complications were analyzed. Follow-up was 4 months.

Results

Two hundred and six patients out of 250 examinations were evaluated. Indications were biliary stones (n = 132), bile duct stenosis (n = 93), stones and stenosis combined (n = 24), and bile duct leakage (n = 1). Of the 117 cases which were suspicious of malignancy, in 99 cases the lesion could be stratified into benign (n = 55) or malignant (n = 44) indicating a sensitivity of 95.5% and a specificity of 94.5% for the indication tumor. SOC-guided biopsies revealed a sensitivity of 57.7% with a specificity of 100%. In 107 examinations, biliary stones were visualized and could be completely removed in 91.1% with a need of three procedures (range 1–6) to achieve final stone clearance. In 75 cases, lithotripsy was performed and was successful in 71 cases (95%). Four out of 45 patients (8.9%) underwent cholecystectomy with surgical bile duct revision as a final therapy. Adverse Event (AE) occurred in 33/250 patients (13.2%) and Serious Adverse Event (SAE) occurred in 1/250 patients (0.4%). Cholangitis was 1% (n = 102) after peri-interventional administration of antibiotics and 12.8% (n = 148) without antibiotic prophylaxis (p < 0.001).

Conclusions

SOC with SpyGlassDS™ became a new standard for the diagnosis of indefinite biliary lesions and therapy of large bile duct stones. The diagnostic yield of SOC-guided biopsies facilitated a definite diagnosis in most cases and should be improved by standardized biopsy protocols. SOC-guided interventions allowed removal of large biliary stones by SOC-guided lithotripsy. The complication rate of 13.2% can be considerably reduced by use of a single-shot antibiotic treatment.



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LapTrain: multi-modality training curriculum for laparoscopic cholecystectomy—results of a randomized controlled trial

Abstract

Background

Multiple training modalities for laparoscopy have different advantages, but little research has been conducted on the benefit of a training program that includes multiple different training methods compared to one method only. This study aimed to evaluate benefits of a combined multi-modality training program for surgical residents.

Methods

Laparoscopic cholecystectomy (LC) was performed on a porcine liver as the pre-test. Randomization was stratified for experience to the multi-modality Training group (12 h of training on Virtual Reality (VR) and box trainer) or Control group (no training). The post-test consisted of a VR LC and porcine LC. Performance was rated with the Global Operative Assessment of Laparoscopic Skills (GOALS) score by blinded experts.

Results

Training (n = 33) and Control (n = 31) were similar in the pre-test (GOALS: 13.7 ± 3.4 vs. 14.7 ± 2.6; p = 0.198; operation time 57.0 ± 18.1 vs. 63.4 ± 17.5 min; p = 0.191). In the post-test porcine LC, Training had improved GOALS scores (+ 2.84 ± 2.85 points, p < 0.001), while Control did not (+ 0.55 ± 2.34 points, p = 0.154). Operation time in the post-test was shorter for Training vs. Control (40.0 ± 17.0 vs. 55.0 ± 22.2 min; p = 0.012). Junior residents improved GOALS scores to the level of senior residents (pre-test: 13.7 ± 2.7 vs. 18.3 ± 2.9; p = 0.010; post-test: 15.5 ± 3.4 vs. 18.8 ± 3.8; p = 0.120) but senior residents remained faster (50.1 ± 20.6 vs. 25.0 ± 1.9 min; p < 0.001). No differences were found between groups on the post-test VR trainer.

Conclusions

Structured multi-modality training is beneficial for novices to improve basics and overcome the initial learning curve in laparoscopy as well as to decrease operation time for LCs in different stages of experience. Future studies should evaluate multi-modality training in comparison with single modalities.

Trial registration: German Clinical Trials Register DRKS00011040



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Endoscopy in Pediatric Inflammatory Bowel Disease: A Position Paper on Behalf of the Porto IBD Group of the Espghan

Endoscopy is a central tool for the evaluation and management of inflammatory bowel disease (IBD). In the last few decades, gastrointestinal (GI) endoscopy has undergone significant technological developments including availability of pediatric-size equipment, enabling comprehensive investigation of the GI tract in children. Simultaneously, professional organization of GI experts have developed guidelines and training programs in pediatric GI endoscopy. This prompted the Porto Group on Pediatric IBD of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) to develop updated guidelines on the role of GI endoscopy in pediatric IBD (PIBD), specifically taking into considerations of recent advances in the diagnosis, disease stratification, and novel therapeutic targets in these patients. Address correspondence and reprint requests to Salvatore Oliva, MD, Department of Pediatrics, Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Viale Regina Elena 324, 00161 Roma – Italy (e-mail: salvatore.oliva@uniroma1.it). Received 17 October, 2017 Accepted 24 June, 2018 DISCLAIMER: ESPGHAN is not responsible for the practices of physicians and provides guidelines and position papers as indicators of best practice only. Diagnosis and treatment is at the discretion of physicians. The authors report no conflicts of interest. © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Retrieval of 28 Rare Earth Magnets from The Small Bowel with Antegrade Single Balloon Enteroscopy

No abstract available

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Considerations in Donor Human Milk Use in Premature Infants

No abstract available

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Nutritional Comparison of Raw, Holder Pasteurized and Shelf-Stable Human Milk Products

Objective: We aim to assess the nutritional composition of shelf-stable human milk and compare the nutritional profile to Holder pasteurized and raw human milk from the same pool. Methods: Milk samples from 60 mothers were pooled. From this pool, 36 samples were taken; 12 samples were kept raw, 12 samples were Holder pasteurized (HP), and 12 samples were retort processed to create a shelf stable product (SS). Samples were analyzed for percent fat, percent solids, total protein, lactose, amino acids, and thiamine. Results: Percent fat, percent solids, and lactose were similar between raw, HP, and SS samples. Total protein was statistically increased in SS samples when compared to raw (p = 0.005) and HP (p 

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Characteristics of HBV-Associated Hepatocellular Carcinoma in Children: A Multi-Center Study

Introduction: Pediatricians and liver specialists in the United States and Canada continue to encounter hepatitis B virus (HBV) infection in high-risk populations, including unvaccinated children, adopted children, and immigrants. Although hepatocellular carcinoma (HCC) is a known complication of HBV, there exists a paucity of data regarding the clinical presentation of HBV-associated HCC in children in these countries. Methods: Investigators at four medical centers with large numbers of HBV-positive children queried their pathology and/or oncology databases to identify all cases of HBV-infected children

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Practices of Introduction of Complementary Feeding and Iron Deficiency Prevention in the Middle East and North Africa

Background: Iron deficiency (ID) with or without anemia is associated with impaired mental and psychomotor development. Given the paucity of information on physicians' knowledge and practices on iron (Fe) supplementation and impact of ID in the Middle East and North Africa (MENA), it was felt important to conduct a survey. Method: A group of expert physicians developed a questionnaire that was randomly distributed among MENA doctors to assess their knowledge and practices on introduction of complementary feeding, impact of ID, its prevention and their impression on prevalence of ID. Descriptive statistics were used. Results: We received 2,444 completed questionnaires. Thirty nine percent of physicians do not follow the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines regarding age of introduction of complementary feedings. Almost 62% estimate the prevalence of ID anemia to be 40–70%, however, only 17% always monitor hemoglobin (Hb) between 9–12 months of age, 43% do so "almost" always while 36% do so "rarely" or (4%) never". For the prevention of ID in infants > 6 months of age, almost all recommend introducing Fe supplements. Ninety seven percent agree that untreated ID during infancy may have long-term negative effects on cognitive function while 53.26% consider that Fe enriched infant cereals result in staining of the baby teeth, constipation and dark stools. Conclusion: Although there is awareness of the impact of ID, there are some misconceptions regarding age of introduction of complementary feedings, surveillance of Fe status and side effects of Fe-enriched infant cereals. There is a need for educational initiatives focusing on Fe deficiency prevention. Address correspondence and reprint requests to Carlos H. Lifschitz, Hospital Italiano de Buenos Aires. Servicio de Gastroenterologia, Hepatologia y Trasplante Infantil. Tte. Gral. Juan Domingo Perón 4230, C1199ABH CABA, Argentina (e-mail: carlos.lifschitz@hiba.org.ar). Received 3 February, 2018 Accepted 25 May, 2018 Collaborators: Sanaa Youssef, Amira Edris, Maher Al-Hatlani, Sheikh Aly, Wafaa Ayesh, Dema Abo Saleh, Soliman Al Saad. Funding: Authors attending the meeting for questionnaire development received support and honoraria from Nestl, Nutrition Institute, Middle East. OPEN Health Dubai and Clinnex CRO were funded by the Nestle Nutrition Institute, Middle East. Contributors: All authors and collaborators developed the survey questionnaire. Leris D'Costa and CL wrote the first draft of the paper. All authors contributed to discussion of the results, review of the manuscript and approved the final manuscript. The authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.jpgn.org). © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Paramedic honored for teaching more than 8K civilians CPR

Dave Kroll has volunteered numerous weekends over the past three years to teach hands-only CPR to the public

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Targeted Chromosomal Rearrangements via Combinatorial Use of CRISPR/Cas9 and Cre/LoxP Technologies in Caenorhabditis elegans

Rearranged chromosomes have been applied to construct genetic balancers to manipulate essential genes in C. elegans. Although much effort has been put into constructing balancer chromosomes, approximately 6% (map units) of the C. elegans genome has not been covered, and this area lies mostly in pairing centers (PCs). Here, we developed a method for conditional chromosomal engineering through combinatorial use of the CRISPR/Cas9 and Cre/LoxP technologies. Functional DNA fragments containing LoxP sequences were inserted into designated genomic loci using a modified counterselection (cs)-CRISPR method. Then, heat-shock-induced Cre recombinase induced an inversion of the chromosomal region between the two LoxP sites. The chromosomal inversions were subsequently detected by the appearance of pharyngeal GFP. Through this method, we have successfully generated several chromosomal inversion lines, providing valuable resources for studying essential genes in pairing centers.



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Upregulation of dNTP Levels After Telomerase Inactivation Influences Telomerase-Independent Telomere Maintenance Pathway Choice in Saccharomyces cerevisiae

In 10–15% of cancers, telomere length is maintained by a telomerase-independent, recombination-mediated pathway called alternative lengthening of telomeres (ALT). ALT mechanisms were first seen, and have been best studied, in telomerase-null Saccharomyces cerevisiae cells called "survivors". There are two main types of survivors. Type I survivors amplify Y' subtelomeric elements while type II survivors, similar to the majority of human ALT cells, amplify the terminal telomeric repeats. Both types of survivors require Rad52, a key homologous recombination protein, and Pol32, a non-essential subunit of DNA polymerase . A number of additional proteins have been reported to be important for either type I or type II survivor formation, but it is still unclear how these two pathways maintain telomeres. In this study, we performed a genome-wide screen to identify novel genes that are important for the formation of type II ALT-like survivors. We identified 23 genes that disrupt type II survivor formation when deleted. 17 of these genes had not been previously reported to do so. Several of these genes (DUN1, CCR4, and MOT2) are known to be involved in the regulation of dNTP levels. We find that dNTP levels are elevated early after telomerase inactivation and that this increase favors the formation of type II survivors.



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The Effect of Balancing Selection on Population Differentiation: A Study with HLA Genes

Balancing selection is defined as a class of selective regimes that maintain polymorphism above what is expected under neutrality. Theory predicts that balancing selection reduces population differentiation, as measured by F$${}_{\hbox{ ST }}$$. However, balancing selection regimes in which different sets of alleles are maintained in different populations could increase population differentiation. To tackle the connection between balancing selection and population differentiation, we investigated population differentiation at the HLA genes, which constitute the most striking example of balancing selection in humans. We found that population differentiation of single nucleotide polymorphisms (SNPs) at the HLA genes is on average lower than that of SNPs in other genomic regions. We show that these results require using a computation that accounts for the dependence of F$${}_{\hbox{ ST }}$$ on allele frequencies. However, in pairs of closely related populations, where genome-wide differentiation is low, differentiation at HLA is higher than in other genomic regions. Such increased population differentiation at HLA genes for recently diverged population pairs was reproduced in simulations of overdominant selection, as long as the fitness of the homozygotes differs between the diverging populations. The results give insight into a possible "divergent overdominance" mechanism for the nature of balancing selection on HLA genes across human populations.



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gQTL: A Web Application for QTL Analysis Using the Collaborative Cross Mouse Genetic Reference Population

Multi-parental recombinant inbred populations, such as the Collaborative Cross (CC) mouse genetic reference population, are increasingly being used for analysis of quantitative trait loci (QTL). However specialized analytic software for these complex populations is typically built in R that works only on command-line, which limits the utility of these powerful resources for many users. To overcome analytic limitations, we developed gQTL, a web accessible, simple graphical user interface application based on the DOQTL platform in R to perform QTL mapping using data from CC mice.



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ovoD Co-selection: A Method for Enriching CRISPR/Cas9-Edited Alleles in Drosophila

Screening for successful CRISPR/Cas9 editing events remains a time consuming technical bottleneck in the field of Drosophila genome editing. This step can be particularly laborious for events that do not cause a visible phenotype, or those which occur at relatively low frequency. A promising strategy to enrich for desired CRISPR events is to co-select for an independent CRISPR event that produces an easily detectable phenotype. Here, we describe a simple negative co-selection strategy involving CRISPR-editing of a dominant female sterile allele, ovoD1. In this system ("ovoD co-selection"), the only functional germ cells in injected females are those that have been edited at the ovoD1 locus, and thus all offspring of these flies have undergone editing of at least one locus. We demonstrate that ovoD co-selection can be used to enrich for knock-out mutagenesis via nonhomologous end-joining (NHEJ), and for knock-in alleles via homology-directed repair (HDR). Altogether, our results demonstrate that ovoD co-selection reduces the amount of screening necessary to isolate desired CRISPR events in Drosophila.



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Genotyping by Sequencing of 393 Sorghum bicolor BTx623 x IS3620C Recombinant Inbred Lines Improves Sensitivity and Resolution of QTL Detection

We describe a genetic map with a total of 381 bins of 616 genotyping by sequencing (GBS)-based SNP markers in a F6-F8 recombinant inbred line (RIL) population of 393 individuals derived from crossing S. bicolor BTx623 to S. bicolor IS3620C, a guinea line substantially diverged from BTx623. Five segregation distorted regions were found with four showing enrichment for S. bicolor alleles, suggesting possible selection during formation of this RIL population. A quantitative trait locus (QTL) study with this number of individuals, tripled relative to prior studies of this cross, provided resources, validated previous findings, and demonstrated improved power to detect plant height and flowering time related QTL relative to other published studies. An unexpected low correlation between flowering time and plant height permitted us to separate QTL for each trait and provide evidence against pleiotropy. Ten non- random syntenic regions conferring QTL for the same trait suggest that those QTL may represent alleles at genes functioning in the same manner since the 96 million year ago genome duplication that created these syntenic relationships, while syntenic regions conferring QTL for different trait may suggest sub-functionalization after duplication. Collectively, this study provides resources for marker-assisted breeding, as well as a framework for fine mapping and subsequent cloning of major genes for important traits such as plant height and flowering time in sorghum.



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Genome-Wide Association and Regional Heritability Mapping of Plant Architecture, Lodging and Productivity in Phaseolus vulgaris

The availability of high-density molecular markers in common bean has allowed to explore the genetic basis of important complex agronomic traits with increased resolution. Genome-Wide Association Studies (GWAS) and Regional Heritability Mapping (RHM) are two analytical approaches for the detection of genetic variants. We carried out GWAS and RHM for plant architecture, lodging and productivity across two important growing environments in Brazil in a germplasm of 188 common bean varieties using DArTseq genotyping strategies. The coefficient of determination of G x E interaction (c2int) was equal to 17, 21 and 41%, respectively for the traits architecture, lodging, and productivity. Trait heritabilities were estimated at 0.81 (architecture), 0.79 (lodging) and 0.43 (productivity), and total genomic heritability accounted for large proportions (72% to 100%) of trait heritability. At the same probability threshold, three marker–trait associations were detected using GWAS, while RHM detected eight QTL encompassing 145 markers along five chromosomes. The proportion of genomic heritability explained by RHM was considerably higher (35.48 to 58.02) than that explained by GWAS (28.39 to 30.37). In general, RHM accounted for larger fractions of the additive genetic variance being captured by markers effects inside the defined regions. Nevertheless, a considerable proportion of the heritability is still missing (~42% to ~64%), probably due to LD between markers and genes and/or rare allele variants not sampled. RHM in autogamous species had the potential to identify larger-effect QTL combining allelic variants that could be effectively incorporated into whole-genome prediction models and tracked through breeding generations using marker-assisted selection.



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Accuracy of Genomic Prediction for Foliar Terpene Traits in Eucalyptus polybractea

Unlike agricultural crops, most forest species have not had millennia of improvement through phenotypic selection, but can contribute energy and material resources and possibly help alleviate climate change. Yield gains similar to those achieved in agricultural crops over millennia could be made in forestry species with the use of genomic methods in a much shorter time frame. Here we compare various methods of genomic prediction for eight traits related to foliar terpene yield in Eucalyptus polybractea, a tree grown predominantly for the production of Eucalyptus oil. The genomic markers used in this study are derived from shallow whole genome sequencing of a population of 480 trees. We compare the traditional pedigree-based additive best linear unbiased predictors (ABLUP), genomic BLUP (GBLUP), BayesB genomic prediction model, and a form of GBLUP based on weighting markers according to their influence on traits (BLUP|GA). Predictive ability is assessed under varying marker densities of 10,000, 100,000 and 500,000 SNPs. Our results show that BayesB and BLUP|GA perform best across the eight traits. Predictive ability was higher for individual terpene traits, such as foliar α-pinene and 1,8-cineole concentration (0.59 and 0.73, respectively), than aggregate traits such as total foliar oil concentration (0.38). This is likely a function of the trait architecture and markers used. BLUP|GA was the best model for the two biomass related traits, height and 1 year change in height (0.25 and 0.19, respectively). Predictive ability increased with marker density for most traits, but with diminishing returns. The results of this study are a solid foundation for yield improvement of essential oil producing eucalypts. New markets such as biopolymers and terpene-derived biofuels could benefit from rapid yield increases in undomesticated oil-producing species.



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Fission Yeast CENP-C (Cnp3) Plays a Role in Restricting the Site of CENP-A Accumulation

The centromere is a chromosomal locus where a microtubule attachment site, termed kinetochore, is assembled in mitosis. In most eukaryotes, with the exception of holocentric species, each chromosome contains a single distinct centromere. A chromosome with an additional centromere undergoes successive rounds of anaphase bridge formation and breakage, or triggers a cell cycle arrest imposed by DNA damage and replication checkpoints. We report here a study in Schizosaccharomyces pombe to characterize a mutant (cnp3-1) in a gene encoding a homolog of mammalian centromere-specific protein, CENP-C. At the restrictive temperature 36°, the Cnp3-1 mutant protein loses its localization at the centromere. In the cnp3-1 mutant, the level of the Cnp1 (a homolog of a centromere-specific histone CENP-A) also decreases at the centromere. Interestingly, the cnp3-1 mutant is prone to promiscuous accumulation of Cnp1 at non-centromeric regions, when Cnp1 is present in excess. Unlike the wild type protein, Cnp3-1 mutant protein is found at the sites of promiscuous accumulation of Cnp1, suggesting that Cnp3-1 may stabilize or promote accumulation of Cnp1 at non-centromeric regions. From these results, we infer the role of Cnp3 in restricting the site of accumulation of Cnp1 and thus to prevent formation of de novo centromeres.



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A Collection of Transgenic Medaka Strains for Efficient Site-Directed Transgenesis Mediated by phiC31 Integrase

Genetic analysis is facilitated by the efficient production of transgenic strains expressing a DNA of interest as a single copy at a designated chromosomal location. However, technical progress toward this goal in medaka fish (Oryzias latipes), a vertebrate model organism, has been slow. It is well known that phiC31 integrase enables efficient site-directed transgenesis by catalyzing the recombination of an attP DNA motif in a host genome with an attB motif in a targeting vector. This system was pioneered in medaka using the Sleeping Beauty transposon system, and the attP site was established at three chromosomal locations. However, this number appeared insufficient with regard to genetic linkage between the attP-landing site and a genetically modified locus of interest. Here, to establish a collection of transgenic strains of medaka, we introduced an attP motif into the medaka genome using the Ac/Ds maize transposon system and established 12 independent transgenic strains harboring a single copy of the attP motif in at least 11 of the 24 medaka chromosomes. We designed an attB-targeting vector that was integrated efficiently and precisely into the attP-landing site, and with which the DNA of interest was efficiently transmitted to germline cells. Extraneous sequences in the integrants derived from the bacterial backbone of the attB-targeting vector as well as a transgenic fluorescence marker present in the attP-landing site were removable through flippase-mediated recombination. Further, an advanced targeting vector with a heart-specific recombination marker served as a useful tool for easily screening phiC31 integrase-mediated recombinant G0 embryos, leading to the efficient establishment of transgenic strains. Thus, our resources advance genetic research in medaka.



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A Missense Mutation in the Vacuolar Protein Sorting 11 (VPS11) Gene Is Associated with Neuroaxonal Dystrophy in Rottweiler Dogs

Canine neuroaxonal dystrophy (NAD) is a recessive, degenerative neurological disease of young adult Rottweiler dogs (Canis lupus familiaris) characterized pathologically by axonal spheroids primarily targeting sensory axon terminals. A genome-wide association study of seven Rottweilers affected with NAD and 42 controls revealed a significantly associated region on canine chromosome 5 (CFA 5). Homozygosity within the associated region narrowed the critical interval to a 4.46 Mb haplotype (CFA5:11.28 Mb – 15.75 Mb; CanFam3.1) that associated with the phenotype. Whole-genome sequencing of two histopathologically confirmed canine NAD cases and 98 dogs unaffected with NAD revealed a homozygous missense mutation within the Vacuolar Protein Sorting 11 (VPS11) gene (g.14777774T > C; p.H835R) that was associated with the phenotype. These findings present the opportunity for an antemortem test for confirming NAD in Rottweilers where the allele frequency was estimated at 2.3%. VPS11 mutations have been associated with a degenerative leukoencephalopathy in humans, and VSP11 should additionally be included as a candidate gene for unexplained cases of human NAD.



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Involvement of YAP-1, the Homolog of Yes-Associated Protein, in the Wnt-Mediated Neuronal Polarization in Caenorhabditis elegans

Guidance molecules, receptors, and downstream signaling pathways involved in the asymmetric neuronal cell migration and process outgrowth have been identified from genetic studies using model organisms, most of which are evolutionarily conserved. In the nematode Caenorhabditis elegans, the roles of Wnt ligands and their receptors in the polarization of specific sets of neurons along the anterior-posterior (A-P) body axis have been well elucidated, but their downstream effectors are relatively unknown. Here, we report yap-1, encoding an evolutionarily conserved transcriptional co-activator, as a novel player in the Wnt-mediated asymmetric development of specific neurons in C. elegans. We found that the loss of yap-1 activity failed to restrict the dendritic extension of ALM neurons to the anterior orientation, which is similar to the phenotype caused by defective cwn-1 and cwn-2 Wnt gene activities. Cell-specific rescue experiments showed that yap-1 acts in the cell autonomous manner to polarize ALM dendrites. We also found that subcellular localization of YAP-1 was spatio-temporally regulated. The loss of yap-1 in Wnt-deficient mutants did not increase the severity of the ALM polarity defect of the mutants. Wnt-deficient animals displayed abnormal subcellular localization of YAP-1 in touch receptor neurons, suggesting that yap-1 may act downstream of the cwn-1/cwn-2 Wnt ligands for the ALM polarization process. Together, we have identified a new role for YAP-1 in neuronal development and our works will contribute to further understanding of intracellular events in neuronal polarization during animal development.



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LIN-12/Notch Regulates GABA Signaling at the Caenorhabditis elegans Neuromuscular Junction

The role of Notch signaling in cell-fate decisions has been studied extensively; however, this pathway is also active in adult tissues, including the nervous system. Notch signaling modulates a wide range of behaviors and processes of the nervous system in the nematode Caenorhabditis elegans, but there is no evidence for Notch signaling directly altering synaptic strength. Here, we demonstrate Notch-mediated regulation of synaptic activity at the C. elegans neuromuscular junction (NMJ). For this, we used aldicarb, an inhibitor of the enzyme acetylcholinesterase, and assessed paralysis rates of animals with altered Notch signaling. Notch receptors LIN-12 and GLP-1 are required for normal NMJ function; they regulate NMJ activity in an opposing fashion. Complete loss of LIN-12 skews the excitation/inhibition balance at the NMJ toward increased activity, whereas partial loss of GLP-1 has the opposite effect. Specific Notch ligands and co-ligands are also required for proper NMJ function. The role of LIN-12 is independent of cell-fate decisions; manipulation of LIN-12 signaling through RNAi knockdown or overexpression of the co-ligand OSM-11 after development alters NMJ activity. We demonstrate that LIN-12 modulates GABA signaling in this paradigm, as loss of GABA signaling suppresses LIN-12 gain-of-function defects. Further analysis, in vivo and in silico, suggests that LIN-12 may modulate transcription of the GABAB receptor GBB-2. Our findings confirm a non-developmental role for the LIN-12/Notch receptor in regulating synaptic signaling and identify the GABAB receptor GBB-2 as a potential Notch transcriptional target in the C. elegans nervous system.



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A Dual sgRNA Approach for Functional Genomics in Arabidopsis thaliana

Reverse genetics uses loss-of-function alleles to interrogate gene function. The advent of CRISPR/Cas9-based gene editing now allows the generation of knock-out alleles for any gene and entire gene families. Even in the model plant Arabidopsis thaliana, gene editing is welcomed as T-DNA insertion lines do not always generate null alleles. Here, we show efficient generation of heritable mutations in Arabidopsis using CRISPR/Cas9 with a workload similar to generating overexpression lines. We obtain for several different genes Cas9 null-segregants with bi-allelic mutations in the T2 generation. While somatic mutations were predominantly generated by the canonical non-homologous end joining (cNHEJ) pathway, we observed inherited mutations that were the result of synthesis-dependent microhomology-mediated end joining (SD-MMEJ), a repair pathway linked to polymerase (PolQ). We also demonstrate that our workflow is compatible with a dual sgRNA approach in which a gene is targeted by two sgRNAs simultaneously. This paired nuclease method results in more reliable loss-of-function alleles that lack a large essential part of the gene. The ease of the CRISPR/Cas9 workflow should help in the eventual generation of true null alleles of every gene in the Arabidopsis genome, which will advance both basic and applied plant research.



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Insights into the Structure of the Spruce Budworm (Choristoneura fumiferana) Genome, as Revealed by Molecular Cytogenetic Analyses and a High-Density Linkage Map

Genome structure characterization can contribute to a better understanding of processes such as adaptation, speciation, and karyotype evolution, and can provide useful information for refining genome assemblies. We studied the genome of an important North American boreal forest pest, the spruce budworm, Choristoneura fumiferana, through a combination of molecular cytogenetic analyses and construction of a high-density linkage map based on single nucleotide polymorphism (SNP) markers obtained through a genotyping-by-sequencing (GBS) approach. Cytogenetic analyses using fluorescence in situ hybridization methods confirmed the haploid chromosome number of n = 30 in both sexes of C. fumiferana and showed, for the first time, that this species has a WZ/ZZ sex chromosome system. Synteny analysis based on a comparison of the Bombyx mori genome and the C. fumiferana linkage map revealed the presence of a neo-Z chromosome in the latter species, as previously reported for other tortricid moths. In this neo-Z chromosome, we detected an ABC transporter C2 (ABCC2) gene that has been associated with insecticide resistance. Sex-linkage of the ABCC2 gene provides a genomic context favorable to selection and rapid spread of resistance against Bacillus thuringiensis serotype kurstaki (Btk), the main insecticide used in Canada to control spruce budworm populations. Ultimately, the linkage map we developed, which comprises 3586 SNP markers distributed over 30 linkage groups for a total length of 1720.41 cM, will be a valuable tool for refining our draft assembly of the spruce budworm genome.



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The Doubletime Homolog KIN-20 Mainly Regulates let-7 Independently of Its Effects on the Period Homolog LIN-42 in Caenorhabditis elegans

The Caenorhabditis elegans (C. elegans) heterochronic pathway, which regulates developmental timing, is thought to be an ancestral form of the circadian clock in other organisms. An essential member of this clock is the Period protein whose homolog, lin-42, in C. elegans is an important heterochronic gene. LIN-42 functions as a transcriptional repressor of multiple genes including the conserved lin-4 and let-7 microRNAs. Like other Period proteins, levels of LIN-42 oscillate throughout development. In other organisms this cycling is controlled in part by phosphorylation. KIN-20 is the C. elegans homolog of the Drosophila Period protein kinase Doubletime. Worms containing a large deletion in kin-20 have a significantly smaller brood size and develop slower than wild type C. elegans. Here we analyze the effect of kin-20 on lin-42 phenotypes and microRNA expression. We find that kin-20 RNAi enhances loss-of-function lin-42 mutant phenotypes and that kin-20 mutant worms express lower levels of LIN-42. We also show that kin-20 is important for post-transcriptional regulation of mature let-7 and lin-4 microRNA expression. In addition, the increased level of let-7 found in lin-42(n1089) mutant worms is not maintained after kin-20 RNAi treatment. Instead, let-7 is further repressed when levels of kin-20 and lin-42 are both decreased. Altogether these results suggest that though kin-20 regulates lin-42 and let-7 microRNA, it mainly affects let-7 microRNA expression independently of lin-42. These findings further our understanding of the mechanisms by which these conserved circadian rhythmic genes interact to ultimately regulate rhythmic processes, developmental timing and microRNA biogenesis in C. elegans.



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RAD Sequencing and a Hybrid Antarctic Fur Seal Genome Assembly Reveal Rapidly Decaying Linkage Disequilibrium, Global Population Structure and Evidence for Inbreeding

Recent advances in high throughput sequencing have transformed the study of wild organisms by facilitating the generation of high quality genome assemblies and dense genetic marker datasets. These resources have the potential to significantly advance our understanding of diverse phenomena at the level of species, populations and individuals, ranging from patterns of synteny through rates of linkage disequilibrium (LD) decay and population structure to individual inbreeding. Consequently, we used PacBio sequencing to refine an existing Antarctic fur seal (Arctocephalus gazella) genome assembly and genotyped 83 individuals from six populations using restriction site associated DNA (RAD) sequencing. The resulting hybrid genome comprised 6,169 scaffolds with an N50 of 6.21 Mb and provided clear evidence for the conservation of large chromosomal segments between the fur seal and dog (Canis lupus familiaris). Focusing on the most extensively sampled population of South Georgia, we found that LD decayed rapidly, reaching the background level by around 400 kb, consistent with other vertebrates but at odds with the notion that fur seals experienced a strong historical bottleneck. We also found evidence for population structuring, with four main Antarctic island groups being resolved. Finally, appreciable variance in individual inbreeding could be detected, reflecting the strong polygyny and site fidelity of the species. Overall, our study contributes important resources for future genomic studies of fur seals and other pinnipeds while also providing a clear example of how high throughput sequencing can generate diverse biological insights at multiple levels of organization.



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A Variable Polyglutamine Repeat Affects Subcellular Localization and Regulatory Activity of a Populus ANGUSTIFOLIA Protein

Polyglutamine (polyQ) stretches have been reported to occur in proteins across many organisms including animals, fungi and plants. Expansion of these repeats has attracted much attention due their associations with numerous human diseases including Huntington's and other neurological maladies. This suggests that the relative length of polyQ stretches is an important modulator of their function. Here, we report the identification of a Populus C-terminus binding protein (CtBP) ANGUSTIFOLIA (PtAN1) which contains a polyQ stretch whose functional relevance had not been established. Analysis of 917 resequenced Populus trichocarpa genotypes revealed three allelic variants at this locus encoding 11-, 13- and 15-glutamine residues. Transient expression assays using Populus leaf mesophyll protoplasts revealed that the 11Q variant exhibited strong nuclear localization whereas the 15Q variant was only found in the cytosol, with the 13Q variant exhibiting localization in both subcellular compartments. We assessed functional implications by evaluating expression changes of putative PtAN1 targets in response to overexpression of the three allelic variants and observed allele-specific differences in expression levels of putative targets. Our results provide evidence that variation in polyQ length modulates PtAN1 function by altering subcellular localization.



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Genomic Selection in Preliminary Yield Trials in a Winter Wheat Breeding Program

Genomic prediction (GP) is now routinely performed in crop plants to predict unobserved phenotypes. The use of predicted phenotypes to make selections is an active area of research. Here, we evaluate GP for predicting grain yield and compare genomic and phenotypic selection by tracking lines advanced. We examined four independent nurseries of F3:6 and F3:7 lines trialed at 6 to 10 locations each year. Yield was analyzed using mixed models that accounted for experimental design and spatial variations. Genotype-by-sequencing provided nearly 27,000 high-quality SNPs. Average genomic predictive ability, estimated for each year by randomly masking lines as missing in steps of 10% from 10 to 90%, and using the remaining lines from the same year as well as lines from other years in a training set, ranged from 0.23 to 0.55. The predictive ability estimated for a new year using the other years ranged from 0.17 to 0.28. Further, we tracked lines advanced based on phenotype from each of the four F3:6 nurseries. Lines with both above average genomic estimated breeding value (GEBV) and phenotypic value (BLUP) were retained for more years compared to lines with either above average GEBV or BLUP alone. The number of lines selected for advancement was substantially greater when predictions were made with 50% of the lines from the testing year added to the training set. Hence, evaluation of only 50% of the lines yearly seems possible. This study provides insights to assess and integrate genomic selection in breeding programs of autogamous crops.



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A Cyclin E Centered Genetic Network Contributes to Alcohol-Induced Variation in Drosophila Development

Prenatal exposure to ethanol causes a wide range of adverse physiological, behavioral and cognitive consequences. However, identifying allelic variants and genetic networks associated with variation in susceptibility to prenatal alcohol exposure is challenging in human populations, since time and frequency of exposure and effective dose cannot be determined quantitatively and phenotypic manifestations are diverse. Here, we harnessed the power of natural variation in the Drosophila melanogaster Genetic Reference Panel (DGRP) to identify genes and genetic networks associated with variation in sensitivity to developmental alcohol exposure. We measured development time from egg to adult and viability of 201 DGRP lines reared on regular or ethanol- supplemented medium and identified polymorphisms associated with variation in susceptibility to developmental ethanol exposure. We also documented genotype-dependent variation in sensorimotor behavior after developmental exposure to ethanol using the startle response assay in a subset of 39 DGRP lines. Genes associated with development, including development of the nervous system, featured prominently among genes that harbored variants associated with differential sensitivity to developmental ethanol exposure. Many of them have human orthologs and mutational analyses and RNAi targeting functionally validated a high percentage of candidate genes. Analysis of genetic interaction networks identified Cyclin E (CycE) as a central, highly interconnected hub gene. Cyclin E encodes a protein kinase associated with cell cycle regulation and is prominently expressed in ovaries. Thus, exposure to ethanol during development of Drosophila melanogaster might serve as a genetic model for translational studies on fetal alcohol spectrum disorder.



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The Relationship Between the Patient-Centered Medical Homes, Healthcare Expenditures, and Quality of Care Among Children with Special Health Care Needs

Abstract

Objectives To examine the association between having a patient-centered medical home (PCMH) and healthcare expenditures and quality of care for children with special health care needs (CSHCN). Methods We conducted a cross-sectional analysis of 8802 CSHCN using the 2008–2012 Medical Expenditure Panel Survey. A PCMH indicator was constructed from survey responses. Inverse probability treatment weighting was applied to balance the cohort. CSHCN's annual health care expenditures and quality were analyzed using two-part and logistic models, respectively. Results Covariate-adjusted annual total expenditures were similar between CSHCN with and without a PCMH ($4267 vs. $3957, p = 0.285). CSHCN with a PCMH had higher odds of incurring expenditure (OR 1.66, 95% CI 1.22–2.25)—in particular, office-based services and prescriptions (OR 1.46 and 1.36, 95% CI 1.24–1.72 and 1.17–1.58, respectively)—compared to those without a PCMH, without shifting expenditures. When examined in detail, PCMH was associated with lower odds of accessing office-based mental health services (OR 0.80, 95% CI 0.66–0.96), leading to lower expenditures ($106 vs. $137; p = 0.046). PCMH was associated with higher odds of post-operation and immunization visits (OR 1.23 and 1.22, 95% CI 1.05–1.45 and 1.004–1.48, respectively) without changing expenditures. Parents of CSHCN with a PCMH were more likely to report having the best health care quality (OR 2.33, p < 0.001). Conclusions CSHCN who had a PCMH experienced better health care quality and were more likely to access preventive services, with unchanged expenditures. However, they were less likely to use mental health services in office-based settings. As the effects of PCMH varied across services for CSHCN, more research is warranted.



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Best Practices for the Design, Implementation and Evaluation of Prenatal Health Programs

Abstract

Introduction Prenatal health programs provide health education, reproductive care and related services to women. Programs may be administered individually or collaboratively by agencies including public health units, hospitals, health clinics, community and non-governmental organizations. Prenatal health disparities among populations at-risk may be reduced through the provision of accessible health education, services and resources to help women mitigate modifiable risks to pregnancy. Although standardized guidelines inform clinical screening, testing and maternity care, gaps exist regarding the design, implementation and evaluation for comprehensive prenatal health programs. Methods Using a multijurisdictional approach, prenatal health guidance documents released by clinical associations and regional governments across Canada, Australia, the United States, the United Kingdom and Ireland were systematically evaluated to identify standards and practices regarding the design, implementation and evaluation of prenatal health programs. Results Evidence-based, surveillance/monitoring, and expert/stakeholder collaborations were principles affirmed by guidance documents across all jurisdictions. Each jurisdiction described tailored strategies to optimize prenatal health in their respective communities. Divergence between jurisdictions was noted for patient care models and promotion of providers and companions of choice. Discussion A best practices model is proposed describing recommendations as follows: prenatal health programs should be grounded in a theoretical approach, fundamentally woman-centered and designed to address interacting prenatal health determinants across the lifespan. Accessible and inclusive prenatal health care can be achieved through provider training and community stakeholder collaborations. Identification of best practices for prenatal health program design, implementation and evaluation ensures that service standards are harmonized across communities, thereby optimizing maternal and child health.



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A quantification of calcaneal lateral plantar process position with implications for bipedal locomotion in Australopithecus

Publication date: Available online 31 July 2018

Source: Journal of Human Evolution

Author(s): Eve K. Boyle, Ellison J. McNutt, Tomohiko Sasaki, Gen Suwa, Bernhard Zipfel, Jeremy M. DeSilva

Abstract

The evolution of bipedalism in the hominin lineage has shaped the posterior human calcaneus into a large, robust structure considered to be adaptive for dissipating peak compressive forces and energy during heel-strike. A unique anatomy thought to contribute to the human calcaneus and its function is the lateral plantar process (LPP). While it has long been known that humans possess a plantarly positioned LPP and apes possess a more dorsally positioned homologous structure, the relative position of the LPP and intraspecific variation of this structure have never been quantified. Here, we present a method for quantifying relative LPP position and find that, while variable, humans have a significantly more plantar position of the LPP than that found in the apes. Among extinct hominins, while the position of the LPP in Australopithecus afarensis falls within the human distribution, the LPP is more dorsally positioned in Australopithecus sediba and barely within the modern human range of variation. Results from a resampling procedure suggest that these differences can reflect either individual variation of a foot structure/function largely shared among Australopithecus species, or functionally distinct morphologies that reflect locomotor diversity in Plio-Pleistocene hominins. An implication of the latter possibility is that calcaneal changes adaptive for heel-striking bipedalism may have evolved independently in two different hominin lineages.



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Serratus Plane Block: A Cadaveric Study to Evaluate Optimal Injectate Spread

Background and Objectives Although serratus plane block reportedly provides satisfactory analgesia for breast and thoracic surgeries, the optimal technique for consistent success has not been studied. The goal of this anatomical study was to evaluate the impact of volume, level, and site of injection on the extent of injectate spread that can influence anesthetic coverage. Methods Ultrasound-guided dye injection and subsequent dissection were performed in 39 cadaveric hemithoraces. Methylene blue was injected according to 1 of 4 injection protocols as follows: one 20-mL bolus, either superficial or deep to the serratus anterior muscle (SAM), at the fifth rib level (groups SUP-20 and DEEP-20, respectively), or two 20-mL boluses, either superior or deep to the SAM, one at the third rib and one at the fifth rib level (group SUP-40 and group DEEP-40, respectively). Following injection, dissection and 3-dimensional digitization were performed to map the area of dye spread. Results We found that the extent of dye spread was mostly influenced by the volume of injection rather than the plane of injection (superficial vs deep to SAM). Increasing the volume from 20 to 40 mL doubled the area of injectate spread and promoted dye spread preferentially to the anterior chest wall, with some impact on cephalad-to-caudad spread and no impact on posterior spread. Dye was found most consistently in the axilla when a separate injection was performed at the third rib level. Conclusions Our data showed that a high-volume double-injection technique provides extensive and consistent dye spread in the anterior chest wall and axilla, regardless of the plane of injection relative to the SAM. This technique likely provides more reliable analgesic coverage for breast procedures especially those that involve the axilla, pending confirmation in future clinical studies. Accepted for publication April 22, 2018. Address correspondence to: Vincent Chan, MD, FRCPC, FRCA, Department of Anesthesia, Toronto Western Hospital, University Health Network, University of Toronto, 399 Bathurst St, MCL 2-405, Toronto, Ontario M5T 2S8, Canada (e-mail: vincent.chan@uhn.ca). V.C. has received honorarium from SonoSite, BBraun, and Aspen Pharma. He also sat on the Medical Advisory Board of Smiths Medical. A.P. has a research grant from Fisher and Pykel for an unrelated study. She is associate editor of Regional Anesthesia and Pain Medicine. A.A. is an anatomy faculty at Allergan Academy of Excellence. The other authors declare no conflict of interest. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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