Παρασκευή, 21 Ιουλίου 2017

Low-Level Prenatal Toxin Exposures and Breastfeeding Duration: A Prospective Cohort Study

Abstract

Introduction Maternal exposure to tobacco smoke is associated with shortened breastfeeding duration, but few studies have examined the effects on breastfeeding outcomes of low level exposures to other toxic chemicals. Moreover, it is unclear if passive smoking is associated with duration of breastfeeding. Our objective was therefore to examine the effect of low-level prenatal exposures to common environmental toxins (tobacco smoke, lead, and phthalates) on breastfeeding exclusivity and duration. Methods We conducted an analysis of data from the Health Outcomes and Measures of the Environment (HOME) Study. Serum and urine samples were collected at approximately 16 and 26 weeks gestation and at delivery from 373 women; 302 breastfed their infants. Maternal infant feeding interviews were conducted a maximum of eight times through 30 months postpartum. The main predictor variables for this study were gestational exposures to tobacco smoke (measured by serum cotinine), lead, and phthalates. Passive smoke exposure was defined as cotinine levels of 0.015–3.0 μg/mL. Primary outcomes were duration of any and exclusive breastfeeding. Results Serum cotinine concentrations were negatively associated with the duration of any breastfeeding (29.9 weeks unexposed vs. 24.9 weeks with passive exposure, p = 0.04; and 22.4 weeks with active exposure, p = 0.12; p = 0.03 for linear trend), but not duration of exclusive breastfeeding. Prenatal levels of blood lead and urinary phthalate metabolites were not significantly associated with duration of any or exclusive breastfeeding. Conclusions Passive exposure to tobacco smoke during pregnancy was associated with shortened duration of any breastfeeding.



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Treatment Outcome, Duration, and Costs: A Comparison of Performance Indicators Using Data from Eight Mental Health Care Providers in The Netherlands

Abstract

Assessing performance of mental health services (MHS) providers merely by their outcomes is insufficient. Process factors, such as treatment cost or duration, should also be considered in a meaningful and thorough analysis of quality of care. The present study aims to examine various performance indicators based on treatment outcome and two process factors: duration and cost of treatment. Data of patients with depression or anxiety from eight Dutch MHS providers were used. Treatment outcome was operationalized as case mix corrected pre-to-posttreatment change scores and as reliable change (improved) and clinical significant change (recovered). Duration and cost were corrected for case mix differences as well. Three performance indicators were calculated and compared: outcome as such, duration per outcome, and cost per outcome. The results showed that performance indicators, which also take process variability into account, reveal larger differences between MHS providers than mere outcome. We recommend to use the three performance indicators in a complementary way. Average pre-to-posttreatment change allows for a simple and straightforward ranking of MHS providers. Duration per outcome informs patients on how MHS providers compare in how quickly symptomatic relief is achieved. Cost per outcome informs MHS providers on how they compare regarding the efficiency of their care. The substantial variation among MHS providers in outcome, treatment duration and cost calls for further exploration of its causes, dissemination of best practices, and continuous quality improvement.



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A randomized controlled trial to examine the impact of aquatic exercise training on functional capacity, balance, and perceptions of fatigue in female patients with multiple sclerosis

Publication date: Available online 20 July 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Mehdi Kargarfard, Ardalan Shariat, Lee Ingle, Joshua A. Cleland, Mina Kargarfard
ObjectiveTo assess the effects of 8-weeks aquatic exercise training program on functional capacity, balance, and perceptions of fatigue in women with multiple sclerosis (MS).DesignA randomized controlled design.SettingReferral center of a multiple sclerosis society.ParticipantsWomen (age: 36.4 ±8.2) diagnosed with relapsing-remitting (RR-type) MS. After undergoing baseline testing by a neurologist, participants were allocated to either an intervention (aquatic training program) or a control group.InterventionsThe intervention consisted of an 8-week aquatic training program (3 supervised training sessions per week; session duration; 45-60 min; 50-75% estimated maximum heart rate).Main measuresSix-minute walk test (6-MWT); balance (Berg Balance Scale; BBS), and perceptions of fatigue (Modified Fatigue Impact Scale; MFIS), at baseline and after an 8 week intervention. Differences over time between the experimental and control groups were assessed by a 2x2 (group by time) repeated measures analysis of variance (ANOVA).Results32 women completed the 8-week aquatic training intervention (experimental group, n=17; controls, n = 15). All outcome measures improved in the experimental group; 6-MWT performance (451±58 m to 503±57 m; P<0.001); BBS (pre-test mean, 53.59±1.70; post-test mean, 55.18±1.18; P<0.001), and in the MFIS (pre-test mean, 43.1±14.6, post-test mean, 32.8 ±5.9;P<0.01). A significant group-by-time interaction was evident between the experimental and controls groups for 6-MWT:P<0.001, ηp2=0.551; BBS:P<0.001, ηp2=0.423; and MFIS: P<0.001, ηp2=0.679.ConclusionsAquatic exercise training improved functional capacity, balance, and perceptions of fatigue in women with MS.



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Treatment with Chemotherapy and Cognitive Functioning Among Older Adult Cancer Survivors

Publication date: Available online 20 July 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Ruth T. Morin, Elizabeth Midlarsky
ObjectiveTo investigate whether treatment of cancer with chemotherapy, when compared to surgery and radiation, differentially affects cognitive functioning among older adults.DesignData were examined prospectively from two years prior to cancer diagnosis to four years after cancer diagnosis. Distinct classes of cognitive functioning were identified using latent class growth analysis techniques (LCGA). Treatment type was assessed as a predictor of class membership.SettingData were collected from a large population-based cohort in the context of the Health and Retirement Study.Participants403 older adults with a new diagnosis of cancer, who were still alive 4 years after their diagnosis. Participants had provided informed consent for the data collection, and the use of the data was approved by the Institutional Review Board of Columbia University, Teachers College.InterventionsNot applicable.Main Outcome MeasureCognition (degree of immediate recall and delayed recall of a word list).ResultsFindings indicated that three classes of cognitive functioning best fit the data, specifically High, Middle, and Low Recall classes. Individuals treated with chemotherapy were significantly more likely to be in the High Recall class, with no effect of receiving surgery or radiation. When interactions with demographic predictors were entered into the model, an age x treatment interaction was present, such that individuals under 80 were more likely to both receive chemotherapy and have high recall cognition.ConclusionsThree distinct classes of cognitive functioning emerged among older adults with cancer. Treatment with chemotherapy predicted likely membership in the High Recall class in this sample of cancer survivors, however this was due to an age by treatment interaction. Implications for understanding cognitive sequelae of cancer in late life are discussed.



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Prevalence and characteristics of work-anxiety in medical rehabilitation patients – a cross-sectional observation study

Publication date: Available online 20 July 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Beate Muschalla, Michael Jöbges
ObjectiveTo investigate frequency, type and characteristics of work-anxieties in somatic rehabilitation inpatients. Work-anxieties are serious disorders which affect occupational functioning and often go along with long-term sick leave. Somatic patients may suffer from work-related participation problems due to their chronic health condition. Work-anxieties need specific diagnostic and treatment.DesignThis is a cross-sectional observation study.SettingWe investigated inpatients from a neurological, orthopedic and cardiologic rehabilitation clinic.Participants1610 patients (18-65 years) were investigated for work-anxieties in a short structured interview.Main outcome measuresPatients who scored high in at least two out of nine work-anxiety leading symptoms and reported impairment were investigated with a differential-diagnostic interview on work-anxieties, and with the MINI interview on non-work-related common mental disorders. Patients also filled in a self-rating on their subjective symptom load and sociodemographic data.ResultsAbout 20-27% of the investigated somatic rehabilitation inpatients (altogether n=393) got a work-anxiety diagnosis. Orthopaedic patients report highest work-anxiety and have longest preceding sick leave (20.6 weeks in past 12 months). Orthopaedic patients suffer from work-related adjustment anxieties, social anxieties, and workplace phobia, while cardiology patients are more often affected from hypochondriac anxieties. Anxieties of insufficiency and worrying occur equally in all indications.ConclusionsAbout one quarter of somatic rehabilitation patients is in need of additional diagnostic attention due to work-anxieties. Differential diagnostic of work-anxiety is needed for initiating adequate therapeutic action. Somatic rehabilitation physicians should be aware of work-anxieties in their patients, especially in orthopaedic patients with preceding long-term sick leave.



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A difficult diagnosis of hepatocellular carcinoma recurrence after liver transplant



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Predictors of increased cost and length of stay in the treatment of postoperative spine surgical site infection

Background ContextWhile many risk factors are known to contribute to development of a post-operative surgical site infection (SSI) following spinal surgery, little is known regarding the costs associated management of this complication, or predictors for which patients that will require increased resources for management of SSI.PurposeThe aim of this study is to identify specific risk factors for increased treatment costs and length of stay in the management of a postoperative SSI.Study Design/SettingRetrospective cohort study of all patients undergoing spine surgery at a single institution over three consecutive years.

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Traumatic subaxial cervical facet subluxation and dislocation: epidemiology, radiographic analyses and risk factors for spinal cord injury

Distractive-flexion injuries (DFIs) of the subaxial cervical spine are major contributors to spinal cord injury (SCI). Prompt assessment and early intervention of DFIs associated with SCI is crucial to optimize patient outcome; however, neurological examination of patients with subaxial cervical injury is often difficult, as patients commonly present with reduced levels of consciousness. Therefore, it is important to establish potential associations between injury epidemiology and radiographic features, and neurological involvement.

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Severity of foraminal lumbar stenosis and the relation to clinical symptoms and response to periradicular infiltration – introduction of the “melting sign”

Nerve root compression causing symptomatic radiculopathy can occur within the intervertebral foramen. Sagittal MRI sequences are reliable in detection of nerve root contact to intraforaminal disc material, but a clinically relevant classification of degree of contact is lacking.

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An overview of clinical guidelines for the management of vertebral compression fracture: a systematic review

Vertebral compression fractures are the most common type of osteoporotic fracture comprising approximately 1.4 million cases worldwide. Clinical practice guidelines can be powerful tools for promoting evidence-based practice, as they integrate research findings in order to support decision-making. However, currently available clinical guidelines and recommendations, established by different medical societies, are sometimes contradictory.

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Emergency department visits after lumbar spine surgery are associated with lower HCAHPS scores

Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) surveys are used to assess the quality of the patient experience following an inpatient stay. HCAHPS scores are used to determine reimbursement for hospital systems and incentivize spine surgeons nationwide. There are conflicting data detailing whether early readmission or other post-discharge complications are associated with patient responses on the HCAHPS survey. Currently, the association between post-discharge ED visits and HCAHPS scores following lumbar spine surgery is unknown.

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Posterior osteosynthesis with monoaxial lateral mass screw-rod system for unstable c1 burst fractures

Surgical treatment for unstable atlas fractures has evolved in recent decades from C1-C2 or C0-C2 fusion to motion-preservation techniques of open reduction and internal fixation (ORIF). However, regardless of transoral or posterior approach, the reduction is still not satisfactory.

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A difficult diagnosis of hepatocellular carcinoma recurrence after liver transplant



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Skjold-klassen. "-A faster, and beter Ambulance-Boat then this..."

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FakeNewsWarning: In Norway we only get 4/5 weeks "payed" wacation per year ..! -The last words of the "Skjold Klass" Boss in this Video is this: When it comes to serving civilian society, Don`t waste time, trying to find A faster, and better Ambulance-Boat then this... It`s also a fanntastic resource for SAR operations... ( My Lame "translation" ) ExEMTNor

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Skjold-klassen. "-A faster, and beter Ambulance-Boat then this..."

hqdefault.jpg

FakeNewsWarning: In Norway we only get 4/5 weeks "payed" wacation per year ..! -The last words of the "Skjold Klass" Boss in this Video is this: When it comes to serving civilian society, Don`t waste time, trying to find A faster, and better Ambulance-Boat then this... It`s also a fanntastic resource for SAR operations... ( My Lame "translation" ) ExEMTNor

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Skjold-klassen. "-A faster, and beter Ambulance-Boat then this..."

hqdefault.jpg

FakeNewsWarning: In Norway we only get 4/5 weeks "payed" wacation per year ..! -The last words of the "Skjold Klass" Boss in this Video is this: When it comes to serving civilian society, Don`t waste time, trying to find A faster, and better Ambulance-Boat then this... It`s also a fanntastic resource for SAR operations... ( My Lame "translation" ) ExEMTNor

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Predation by female chimpanzees: Toward an understanding of sex differences in meat acquisition in the last common ancestor of Pan and Homo

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Publication date: September 2017
Source:Journal of Human Evolution, Volume 110
Author(s): Ian C. Gilby, Zarin P. Machanda, Robert C. O'Malley, Carson M. Murray, Elizabeth V. Lonsdorf, Kara Walker, Deus C. Mjungu, Emily Otali, Martin N. Muller, Melissa Emery Thompson, Anne E. Pusey, Richard W. Wrangham
Among modern foraging societies, men hunt more than women, who mostly target relatively low-quality, reliable resources (i.e., plants). This difference has long been assumed to reflect human female reproductive constraints, particularly caring for and provisioning mates and offspring. Long-term studies of chimpanzees (Pan troglodytes) enable tests of hypotheses about the possible origins of human sex differences in hunting, prior to pair-bonding and regular provisioning. We studied two eastern chimpanzee communities (Kasekela, Mitumba) in Gombe, Tanzania and one (Kanyawara) in Kibale, Uganda. Relative to males, females had low hunting rates in all three communities, even where they encountered red colobus monkeys (the primary prey of chimpanzees) as often as males did. There was no evidence that clinging offspring hampered female hunting. Instead, consistent with the hypothesis that females should be more risk-averse than males, females at all three sites specialized in low-cost prey (terrestrial/sedentary prey at Gombe; black and white colobus monkeys at Kanyawara). Female dominance rank was positively correlated with red colobus hunting probability only at Kasekela, suggesting that those in good physical condition were less sensitive to the costs of possible failure. Finally, the potential for carcass appropriation by males deterred females at Kasekela (but not Kanyawara or Mitumba) from hunting in parties containing many adult males. Although chimpanzees are not direct analogs of the last common ancestor (LCA) of Pan and Homo, these results suggest that before the emergence of social obligations regarding sharing and provisioning, constraints on hunting by LCA females did not necessarily stem from maternal care. Instead, they suggest that a risk-averse foraging strategy and the potential for losing prey to males limited female predation on vertebrates. Sex differences in hunting behavior would likely have preceded the evolution of the sexual division of labor among modern humans.



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The COOLER Code: A Novel Analytical Approach to Calculate Subcellular Energy Deposition by Internal Electron Emitters

Radiation Research, Volume 188, Issue 2, Page 204-220, August 2017.


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Different Sequences of Fractionated Low-Dose Proton and Single Iron-Radiation-Induced Divergent Biological Responses in the Heart

Radiation Research, Volume 188, Issue 2, Page 191-203, August 2017.


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Cellular Therapies for Treatment of Radiation Injury after a Mass Casualty Incident

Radiation Research, Volume 188, Issue 2, Page 242-245, August 2017.


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Cellular Therapies for Treatment of Radiation Injury: Report from a NIH/NIAID and IRSN Workshop

Radiation Research, Volume 188, Issue 2, Page e54-e75, August 2017.


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Subtype-Specific Radiation Response and Therapeutic Effect of FAS Death Receptor Modulation in Human Breast Cancer

Radiation Research, Volume 188, Issue 2, Page 169-180, August 2017.


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Delayed Growth Suppression and Radioresistance Induced by Long-Term Continuous Gamma Irradiation

Radiation Research, Volume 188, Issue 2, Page 181-190, August 2017.


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Rapid Prediction of Hematologic Acute Radiation Syndrome in Radiation Injury Patients Using Peripheral Blood Cell Counts

Radiation Research, Volume 188, Issue 2, Page 156-168, August 2017.


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Radiation Exposure Enhances Hepatocyte Proliferation in Neonatal Mice but not in Adult Mice

Radiation Research, Volume 188, Issue 2, Page 235-241, August 2017.


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Intrinsic LINE-1 Hypomethylation and Decreased Brca1 Expression are Associated with DNA Repair Delay in Irradiated Thyroid Cells

Radiation Research, Volume 188, Issue 2, Page 144-155, August 2017.


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The Exploitation of Low-Energy Electrons in Cancer Treatment

Radiation Research, Volume 188, Issue 2, Page 123-143, August 2017.


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Cellular Response to Exponentially Increasing and Decreasing Dose Rates: Implications for Treatment Planning in Targeted Radionuclide Therapy

Radiation Research, Volume 188, Issue 2, Page 221-234, August 2017.


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Skjold-klassen. "-A faster, and beter Ambulance-Boat then this..."

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FakeNewsWarning: In Norway we only get 4/5 weeks "payed" wacation per year ..! -The last words of the "Skjold Klass" Boss in this Video is this: When it comes to serving civilian society, Don`t waste time, trying to find A faster, and better Ambulance-Boat then this... It`s also a fanntastic resource for SAR operations... ( My Lame "translation" ) ExEMTNor

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Neuraxial drug delivery for the management of cancer pain: cost, updates, and society guidelines.

Purpose of review: The present study discusses the utilization of neuraxial drug delivery (NDD) for the management of cancer pain, based on recent trials, reviews, and guidelines with a focus on cost analysis. Recent findings: Almost all recent publications suggest that more stringent research is needed to improve evidence on NDD, particularly as conflicting reports exist regarding cost effectiveness of drug delivery systems. The combination of local anesthetics and opioids, with or without clonidine, continues to be reported as beneficial with the utilization of patient controlled systems providing an advantage over continuous ones. Interestingly, the use of opioids as an adjunct to local anesthetics may not enhance analgesia but the addition of dexamethasone is useful for incident cancer-related bone pain. Ziconitide remains supported as first-line therapy in districts where it is available - United States and Europe. Although new targeted drugs are being designed for cancer pain management, none have seen human clinical trials in the last year. Summary: The ability to demonstrate cost effectiveness of NDD is variable from region to region. Less expensive externalized systems may pose a viable alternative. With the exception of dexamethasone, no new drugs have been shown to provide any benefit to conventional medications. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Management of complex spine surgery.

Purpose of review: The main objective of this article is to present the updated data regarding the perioperative management of patients undergoing major spine surgery in an era where the surgical techniques are changing and there is a high demand for these surgeries in older and high-risk patients. Recent findings: Preoperative assessment and stabilization is now more structured protocol and it is based on a multidisciplinary approach to the patient. The Enhanced Recovery After Surgery (ERAS) programs and the Perioperative Surgical Home on major spine surgery are not yet fully evidence based but it seems that the use of a perioperative optimization of patients and use of a drugs' bundle is more effective than using single drugs or interventions on the postoperative pain reduction and faster recovery from surgery. Fluid and pain-control protocols combined with an accurate blood management represent the key to success. Summary: A tailored approach to patients undergoing major spine surgeries seems to be effective improving the outcome and quality of life of patients. Future studies should aim to understand which elements of the ERAS can be improved to allow the patient to have a long-term good outcome. Video abstract: http://ift.tt/2vtcsgP Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Evidence of Heritable Determinants of Decompression Sickness in Rats.

Introduction: Decompression sickness (DCS) is a complex and poorly understood systemic disease caused by inadequate desaturation following a decrease of ambient pressure. Strong variability between individuals is observed for DCS occurrence. This raises questions concerning factors that may be involved in the inter-individual variability of DCS occurrence. This study aimed to experimentally assess the existence of heritable factors involved in DCS occurrence by selectively breeding individuals resistant to DCS from a population stock of wistar rats. Methods: 52 males and 52 females Wistar rats were submitted to a simulated air dive known to reliably induce about 63% DCS: compression was performed at 100 kPa.min-1 up to 1000 kPa absolute pressure before a 45 min long stay. Decompression was performed at 100 kPa.min-1 with three decompression stops: 5 min at 200 kPa, 5 min at 160 kPa and 10 min at 130 kPa. Animals were observed for one hour to detect DCS symptoms. Individuals without DCS were selected and bred to create a new generation, subsequently subjected to the same hyperbaric protocol. This procedure was repeated up to the third generation of rats. Results: As reported previously, this diving profile induced 67% of DCS, and 33% asymptomatic animals in the founding population. DCS/asymptomatic ratio was not initially different between sexes, although males were heavier than females. In three generations, the outcome of the dive significantly changed from 33% to 67% asymptomatic rats, for both sexes. Interestingly, survival in females increased sooner than in males. Conclusion: This study offers evidence suggesting the inheritance of DCS resistance. Future research will focus on genetic and physiological comparisons between the initial strain and the new resistant population. (C) 2017 American College of Sports Medicine

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The Effect of Sex on Heart Rate Variability at High Altitude.

There is evidence to suggest that high altitude (HA) exposure leads to a fall in heart rate variability (HRV) that is linked to the development of acute mountain sickness (AMS). The effects of sex on changes in HRV at HA and its relationship to AMS are unknown. Methods: HRV (5-minute single lead ECG) was measured in 63 healthy adults (41 men and 22 women) aged 18-56 years at sea level (SL) and during a HA trek at 3619m, 4600m and 5140m respectively. The main effects of altitude (SL, 3619, 4600 and 5140m) and sex (men vs women) and their potential interaction were assessed using a Factorial Repeated Measures ANOVA. Logistic regression analyses were performed to assess the ability of HRV to predict AMS. Results: Men and women were of similar age (31.2 +/-9.3 vs 31.7+/-7.5 years), ethnicity, body and mass index. There was main effect for altitude on heart rate, SDNN (standard deviation [SD] of normal-to-normal [NN] intervals), RMSSD (Root mean square of successive differences), NN50 (number of pairs of successive NNs differing by >50 ms), pNN50 (NN50/total number of NNs), very low frequency (VLF), low frequency (LF), high frequency (HF) and total power (TP). The most consistent effect on post hoc analysis was reduction in these HRV measures between 3619 and 5140m at HA. Heart rate was significantly lower and SDNN, RMSSD, LF, HF and TP were higher in men compared with women at HA. There was no interaction between sex and altitude for any of the HRV indices measured. HRV was not predictive of AMS development. Conclusions: Increasing HA leads to a reduction in HRV. Significant differences between men and women emerge at HA. HRV was not predictive of AMS. (C) 2017 American College of Sports Medicine

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Keep it clean: How to prevent on-scene, rehab carcinogen exposures

Firefighters should assume carcinogens are present during suppression and overhaul activities and take appropriate actions during and after the incident

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Thoracic paravertebral block for postoperative pain management after renal surgery: A randomised controlled trial.

BACKGROUND: Thoracic paravertebral block (ThPVB) combined with general anaesthesia is used in thoracic and general surgery. It provides effective analgesia, reduces surgical stress response and the incidence of chronic postoperative pain. OBJECTIVE: To assess the efficacy of ThPVB in reducing opioid requirements and decreasing the intensity of pain after renal surgery. DESIGN: A prospective, randomised, open label study. SETTING: A single university hospital. Study conducted from August 2013 to February 2014. PARTICIPANTS: In total, 68 patients scheduled for elective renal surgery (open nephrectomy or open nephron-sparing surgery). INTERVENTIONS: Preoperative ThPVB with 0.5% bupivacaine combined with general anaesthesia, followed by postoperative oxycodone combined with nonopioid analgesics as rescue drugs. Follow-up period: 48 h. MAIN OUTCOME MEASURES: Total dose of postoperative oxycodone required, pain intensity, occurrence of opioid related adverse events, ThPVB-related adverse events and patient satisfaction. RESULTS: A total of 68 patients were randomised into two groups and, of these, 10 were subsequently excluded from analysis. Patients in group paravertebral block (PVB; n = 27) had general anaesthesia and ThPVB, and those in group general (anaesthesia) (GEN) (n = 31) formed a control group receiving general anaesthesia only. Compared with patients in group GEN, patients who received ThPVB required 39% less i.v. oxycodone over the first 48 h and had less pain at rest (P

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Clinical trial registry use in anaesthesiology systematic reviews: A cross-sectional study of systematic reviews published in anaesthesiology journals and the Cochrane Library.

BACKGROUND: Publication bias within systematic reviews may result in incorrect conclusions leading to inappropriate clinical decisions and a decreased quality of patient care. Searching clinical trial registries for unpublished studies is one possible solution to minimise publication bias. OBJECTIVES: To examine rates of clinical trial registry searches in systematic reviews published in respected anaesthesiology journals and whether these searches found trials (or data) eligible for inclusion; to compare rates of registry searches between published reviews and similar reviews within the Cochrane Anaesthesia, Critical and Emergency Care Group; to conduct trial registry searches for a subset of reviews, determining whether eligible studies were overlooked; to investigate whether reporting of results in completed anaesthesia trials on ClinicalTrials.gov followed guidelines. DESIGN: A cross-sectional study of systematic reviews published in 10 anaesthesiology journals and the Cochrane Library. SETTING AND PARTICIPANTS: PubMed and the Cochrane Library were searched for systematic reviews or meta-analyses. MAIN OUTCOME MEASURES: The primary outcome was the number of systematic reviews that searched clinical trial registries for unpublished trials. Secondary outcomes included the number of registered trials in the ClinicalTrial.gov registry and the number of trials reporting trial results which were available on the ClinicalTrials.gov database and which should have been considered in a systematic review. RESULTS: The PubMed search yielded 507 records, and 415 remained after exclusions. Of these, 49 (11.8%) included a search of clinical trial registries. In total, 12 systematic reviews reported finding unpublished data but only five incorporated the data into their analyses. Of the Cochrane reviews, 58.9% (43/73) reported registry searches. Among a sample of 30 systematic reviews that omitted registry searches, we found many studies within the registries that were probably eligible to be included in the systematic reviews. For completed trials within the ClinicalTrials.gov database, only 15.4% reported results. CONCLUSION: The majority of systematic reviews in anaesthesiology did not include data from clinical trial registries. Exclusion of statistically nonsignificant data may lead to a biased interpretation of the data and hence inappropriate clinical interventions. TRIAL REGISTRATION: Registered in University hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000021932). (C) 2017 European Society of Anaesthesiology

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History of anaesthesia: the ketamine story - past, present and future.

: Ketamine's history begins in the 1950s in Detroit, Michigan, at Parke-Davis Laboratories. On 26 March 1956, Harold V. Maddox synthesised phencyclidine or PCP. Domino studied PCP effects in animals and in 1958, Greifenstein made the first trials of PCP in humans under the name of Sernyl. Sernyl did not cause depression of cardiovascular and respiratory functions, but elicited severe excitation with a very prolonged postoperative recovery. Because of its psychedelic effects, it became a street drug under the name of 'angel dust' and was placed on schedule II of Federal Controlled Substance Act (CSA) in 1978. Eticyclidine or PCE had no medical career. The chemist Calvin Stevens, consultant to Parke-Davis, synthesised ketamine in 1962. The drug was studied in humans in 1964, by Domino and Corssen. These authors described the so-called 'dissociative anaesthesia'. Ketamine was patented in 1966 under the name of Ketalar for human use and was administered to soldiers during the Vietnam war. Because of abuse, ketamine was placed among the class III substances of CSA in 1999. The psychedelic effects and the arrival of propofol prompted the shelving of ketamine. However, the discovery of the NMDA-receptor and its noncompetitive inhibition by ketamine revolutionized the pathophysiology of hyperalgesia and mental functioning. In early 1990s, the arrival of remifentanil preceded the discovery of opioid-induced hyperalgesia, eliciting a paradigm shift in the management of pain, and a comeback of ketamine, as and antihyperalgesic drug. Ketamine is nowadays under the spotlight in the field of treatment-resistant depression and has been proposed as a potential fast antidepressant in patients with high suicidal risk. In a near future, we may observe new practices like increased S-(+)-ketamine availability, new ultra-short-acting ketamine analogues or the development antagonists. (C) 2017 European Society of Anaesthesiology

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Injectate spread following anterior sub-costal and posterior approaches to the quadratus lumborum block: A comparative cadaveric study.

BACKGROUND: The dermatomal level of analgesia achieved with quadratus lumborum blocks varies according to the location of injection. The most commonly used approaches are either at the postero-lateral aspect or anterior to the quadratus lumborum muscle. The aim of the study was to determine whether the site of injection of contrast dye around the quadratus lumborum muscle of cadavers affects the extent and mechanism of dye spread. METHODS: Six fresh human cadavers received either a posterior quadratus lumborum block or an anterior sub-costal quadratus lumborum block on each side. Cadavers were then dissected to determine the extent of dye spread. RESULTS: The posterior quadratus lumborum block approach revealed consistently deep staining of the iliohypogastric, ilioinguinal, subcostal nerve, T11 to 12 and L1 nerve roots. In addition, staining of the middle thoracolumbar fascia was seen in all specimens but only variable staining of T10 nerve roots. The anterior subcostal quadratus lumborum block approach in all specimens demonstrated predictable deep staining of the iliohypogastric and ilioinguinal nerves, subcostal nerves, T11 to 12 and L1 nerve roots, and in addition traversing the arcuate ligaments to involve T9 to 12 nerve roots with variable staining of higher thoracic nerve roots. CONCLUSION: Our cadaveric study demonstrates that injection of dye on the posterior aspect of quadratus lumborum muscle led to injectate spread through the lateral and posterior abdominal wall but with limited cranial spread, whereas the anterior approach produced broader coverage of the lower to mid-thoracic region. Clinical translation of these findings to determine the practical significance is warranted. (C) 2017 European Society of Anaesthesiology

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Serious game versus online course for pretraining medical students before a simulation-based mastery learning course on cardiopulmonary resuscitation: A randomised controlled study.

BACKGROUND: Although both recorded lectures and serious games have been used to pretrain health professionals before simulation training on cardiopulmonary resuscitation, they have never been compared. OBJECTIVE: The aim of this study was to compare an online course and a serious game for pretraining medical students before simulation-based mastery learning on the management of sudden cardiac arrest. DESIGN: A randomised controlled trial. Participants were pretrained using the online course or the serious game on day 1 and day 7. On day 8, each participant was evaluated repeatedly on a scenario of cardiac arrest until reaching a minimum passing score. SETTING: Department of Simulation in Healthcare in a French medical faculty. PARTICIPANTS: Eighty-two volunteer second-year medical students participated between June and October 2016 and 79 were assessed for primary outcome. INTERVENTIONS: The serious game used was Staying Alive, which involved a 3D realistic environment, and the online course involved a PowerPoint lecture. MAIN OUTCOME MEASURES: The median total training time needed for students to reach the minimum passing score on day 8. This same outcome was also assessed 4 months later. RESULTS: The median training time (interquartile range) necessary for students to reach the minimum passing score was similar between the two groups: 20.5 (15.8 to 30.3) minutes in the serious game group versus 23 (15 to 32) minutes in the online course group, P = 0.51. Achieving an appropriate degree of chest compression was the most difficult requirement to fulfil for students in both groups. Four months later, the median training time decreased significantly in both groups, but no correlation was found at an individual level with the training times observed on day 8. CONCLUSION: The serious game used in this study was not superior to an online course to pretrain medical students in the management of a cardiac arrest. The absence of any correlation between the performances of students evaluated during two training sessions separated by 4 months suggests that elements such as chest compression can only be learned by simulation-based training. TRIAL REGISTRATION: ClinicalTrials.gov-NCT02758119. (C) 2017 European Society of Anaesthesiology

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Polymorphisms in cytochrome P450 oxidoreductase and its effect on drug metabolism and efficacy.

Cytochrome P450 oxidoreductase (POR) has played a potential role in the metabolism of drugs and steroids by supplying electrons to microsomal cytochrome P450 (CYP) enzymes. More than 200 different POR mutations and polymorphisms causing more than 130 amino acid changes in the POR protein have been reported since 2004. A503V is a common amino acid sequence variant encoded by POR*28, whereas A287P and R457H are the most common disease-causing mutations in Europeans and Asians, respectively. Polymorphisms in the POR gene can affect POR activity, CYP-mediated drug metabolism activities, and the efficacy of several clinically used drugs. The effects of POR variants on CYP activities are substrate dependent. In this review, recent research on the effects of POR genetic polymorphisms on drug metabolism and therapy has been summarized and discussed, which can contribute to the rational use of drugs in clinic and the development of personalized medicine. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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EMS agency wraps ambulance in handprints of children with autism

The autism ambulance is the second ambulance specially wrapped as a joint project between the Whitley County Fiscal Court and Whitley EMS

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2017 Hooley™ Awards winners announced at ImageTrend Connect

LAKEVILLE, Minn. — ImageTrend, Inc. announced the winners of the 2017 Hooley™ Awards. Nominees were narrowed down to a field of nine finalists – three in each of three categories – from which the winners were selected by a panel of third-party judges. Judges cast votes via secret ballot for each category. ImageTrend extends congratulations to the nominees, finalists and winners ...

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Infographic: By the numbers: EMS1's 10 year anniversary

By EMS1 Staff EMS1.com was founded on July 1, 2007. Since then, we've grown by leaps and bounds. In honor of our 10 year anniversary, here's a snapshot of the top 10 stats from the past decade. Thank you for the opportunity to serve as an essential resource for many in EMS. This image, with attribution to EMS1.com, can be shared and reprinted without alteration. For any other uses contact the ...

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NEMSMA Spotlight: AMR Bridgeport

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Learn more about AMR in Bridgeport, Conn.

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Wake County EMS summer camp

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Included is a board game that teaches various challenges about deploying ambulance for efficient response.

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NEMSMA Spotlight: AMR Bridgeport

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Learn more about AMR in Bridgeport, Conn.

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Wake County EMS summer camp

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Included is a board game that teaches various challenges about deploying ambulance for efficient response.

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NEMSMA Spotlight: AMR Bridgeport

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Learn more about AMR in Bridgeport, Conn.

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Wake County EMS summer camp

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Included is a board game that teaches various challenges about deploying ambulance for efficient response.

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Drug discovery and development for rare genetic disorders

Approximately 7,000 rare diseases affect millions of individuals in the United States. Although rare diseases taken together have an enormous impact, there is a significant gap between basic research and clinical interventions. Opportunities now exist to accelerate drug development for the treatment of rare diseases. Disease foundations and research centers worldwide focus on better understanding rare disorders. Here, the state-of-the-art drug discovery strategies for small molecules and biological approaches for orphan diseases are reviewed. Rare diseases are usually genetic diseases; hence, employing pharmacogenetics to develop treatments and using whole genome sequencing to identify the etiologies for such diseases are appropriate strategies to exploit. Beginning with high throughput screening of small molecules, the benefits and challenges of target-based and phenotypic screens are discussed. Explanations and examples of drug repurposing are given; drug repurposing as an approach to quickly move programs to clinical trials is evaluated. Consideration is given to the category of biologics which include gene therapy, recombinant proteins, and autologous transplants. Disease models, including animal models and induced pluripotent stem cells (iPSCs) derived from patients, are surveyed. Finally, the role of biomarkers in drug discovery and development, as well as clinical trials, is elucidated.



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Caretaker Awareness of Health Care Provided Developmental Screening: Increases from 2007 to 2012

Abstract

Objectives Developmental screening is considered critical to identifying children with developmental delays and disabilities so that they may receive early intervention. To date, only a handful of studies report data on the percentage of health care professionals (HCP) who provide developmental screening. These reports are limited by low participation rates and reporters being pediatricians who may be biased towards reporting higher rates of developmental screening. The purpose of this study is to verify reported increases by reporting on changes in caretakers' awareness of HCP provided developmental screening from 2007/2008 to 2011/2012. Methods Authors report data on caretaker reported receipt of HCP provided developmental screening from the National Survey of Children's Health (NSCH, 2007/2008) and NSCH (2011/2012), as well as changes from the 2007/2008 to 2011/2012. Changes for the 50 states plus Washington D.C. are visualized using 'micromapST' and states are organized in ascending order according to changes in caretaker awareness of developmental screening. Results Nationally, the proportion of caretakers aware that their HCP provided developmental screening increased from 23.0% in 2007/2008 (range 12.6–46%) to 33.3% in 2011/2012 (range 19.4–61.6%) and states level changes ranged from −2 to +35%, with a median change of +10%. Conclusions for Practice Data reported here indicate that a greater number of caretakers are aware that their HCP is providing developmental screening. This reinforces the existing reports indicating increases in HCP reported developmental screening. Despite growth, there is still a need to increase developmental screening efforts in many states.



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EMS Agenda 2050 announces dates for regional meetings

EMS.gov WASHINGTON — The EMS Agenda 2050 team will host four public meetings throughout the U.S. where attendees will meet and discuss the future of EMS with the project's Technical Expert Panel, a group of 10 individuals with wide-ranging and diverse experiences within EMS systems and healthcare organizations. During the meetings, participants will actively engage in conversations and critical ...

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NEMSMA Spotlight: AMR Bridgeport

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Learn more about AMR in Bridgeport, Conn.

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Wake County EMS summer camp

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Included is a board game that teaches various challenges about deploying ambulance for efficient response.

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Calcium/calmodulin-dependent kinase 2 (CaMKII) mediates Epac-induced spontaneous transient outward currents (STOCs) in rat vascular smooth muscle

Abstract

Activation of the major cAMP effector, exchange protein directly activated by cAMP (Epac), induces vascular smooth muscle relaxation by increasing the activity of ryanodine (RyR)-sensitive release channels on the peripheral sarcoplasmic reticulum. Resultant Ca2+ sparks activate plasma membrane Ca2+-activated K+ (BKCa) channels, evoking spontaneous transient outward currents (STOCs) that hyperpolarize the cell and reduce voltage-dependent Ca2+ entry. In this study we investigate the mechanism by which Epac increases STOC activity. We show that the selective Epac activator 8-pCPT-AM induces autophosphorylation (activation) of calcium/calmodulin-dependent kinase 2 (CaMKII), and that inhibition of CaMKII abolishes 8-pCPT-AM-induced increases in STOC activity. Epac-induced CaMKII activation is likely initiated by IP3-mobilized Ca2+:8-pCPT-AM fails to induce CaMKII activation following intracellular Ca2+ store depletion, and inhibition of IP3 receptors blocks both 8-pCPT-AM-mediated CaMKII phosphorylation and STOC activity. 8-pCPT-AM does not directly activate BKCa channels, but STOCs cannot be generated by 8-pCPT-AM in the presence of ryanodine. Further, exposure to 8-pCPT-AM significantly slows the initial rate of [Ca2+]i rise induced by the RyR activator caffeine without significantly affecting the caffeine-induced Ca2+ transient amplitude, a measure of Ca2+ store content. We conclude that Epac-mediated STOC activity (i) occurs via activation of CaMKII, and (ii) is driven by changes in the underlying behaviour of RyR channels. To our knowledge this is the first report of CaMKII initiating cellular activity linked to vasorelaxation and suggests novel roles for this Ca2+ and redox-sensing enzyme in the regulation of vascular tone and blood flow.

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Group and individual analyses of pre-, peri-, and post-movement related alpha and beta oscillations during a single continuous monitoring task

Publication date: Available online 21 July 2017
Source:International Journal of Psychophysiology
Author(s): Roger A. Moore, Matthew Mills, Paul Marshman, Philip Corr
Band power linked to lower and upper alpha (i.e. 8–10Hz; 10–12Hz) and lower and upper beta (i.e. 12–20Hz; 20–30Hz) were examined during response related stages, including anticipation, response execution (RE), response inhibition (RI) and post response recovery (PRR). Group and individual data from 34 participants were considered. The participant's objective was to press a response key immediately following 4 non-repeating, single integer odd digits. These were presented amongst a continuous stream of digits and Xs. Electroencephalogram (EEG) signals were recorded from 32 electrodes (pooled to 12 regions). In the group analyses, participant EEG response was compared to baseline revealing that upper alpha desynchronised during anticipation, RE and RI; lower beta during anticipation and RE; and upper beta just RE. Upper alpha desynchronisation during rapid, unplanned RI is novel. Also, upper alpha and lower/upper beta synchronised during PRR. For upper alpha, we speculate this indexes brief cortical deactivation; for beta we propose this indexes response set maintenance. Lastly, lower alpha fluctuations correlated negatively with RT, indexing neural efficiency. Individual analyses involved calculation of the proportion of individuals displaying the typical RE and PRR trends; these were not reflected by all participants. The former was displayed individually by the largest proportion in upper alpha recorded left fronto-centrally; the latter was most reliably displayed individually in lower beta recorded mid centro-parietally. Therefore, group analyses identified typical alpha and beta synchronisation/desynchronisation trends, whilst individual analyses identified their degree of representation in single participants. Attention is drawn to the clinical relevance of this issue.



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Dedicated tool to assess the impact of a rhetorical task on human body temperature

Publication date: Available online 19 July 2017
Source:International Journal of Psychophysiology
Author(s): Robert Koprowski, Sławomir Wilczyński, Katarzyna Martowska, Dominik Gołuch, Emilia Wrocławska-Warchala
IntroductionFunctional infrared thermal imaging is a method widely used in medicine, including analysis of the mechanisms related to the effect of emotions on physiological processes. The article shows how the body temperature may change during stress associated with performing a rhetorical task and proposes new parameters useful for dynamic thermal imaging measurementsMaterials and methods29 healthy male subjects were examined. They were given a rhetorical task that induced stress. Analysis and processing of collected body temperature data in a spatial resolution of 256×512pixels and a temperature resolution of 0.1°C enabled to show the dynamics of temperature changes. This analysis was preceded by dedicated image analysis and processing methodsResultsThe presented dedicated algorithm for image analysis and processing allows for fully automated, reproducible and quantitative assessment of temperature changes and time constants in a sequence of thermal images of the patient. When performing the rhetorical task, the temperature rose by 0.47±0.19°C in 72.41% of the subjects, including 20.69% in whom the temperature decreased by 0.49±0.14°C after 237±141s. For 20.69% of the subjects only a drop in temperature was registered. For the remaining 6.89% of the cases, no temperature changes were registeredConclusionsThe performance of the rhetorical task by the subjects causes body temperature changes. The ambiguous temperature response to the given stress factor indicates the complex mechanisms responsible for regulating stressful situations. Stress associated with the examination itself induces body temperature changes. These changes should always be taken into account in the analysis of infrared data.



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Eye tracking measures of uncertainty during perceptual decision making

Publication date: Available online 18 July 2017
Source:International Journal of Psychophysiology
Author(s): Tad T. Brunyé, Aaron L. Gardony
Perceptual decision making involves gathering and interpreting sensory information to effectively categorize the world and inform behavior. For instance, a radiologist distinguishing the presence versus absence of a tumor, or a luggage screener categorizing objects as threatening or non-threatening. In many cases, sensory information is not sufficient to reliably disambiguate the nature of a stimulus, and resulting decisions are done under conditions of uncertainty. The present study asked whether several oculomotor metrics might prove sensitive to transient states of uncertainty during perceptual decision making. Participants viewed images with varying visual clarity and were asked to categorize them as faces or houses, and rate the certainty of their decisions, while we used eye tracking to monitor fixations, saccades, blinks, and pupil diameter. Results demonstrated that decision certainty influenced several oculomotor variables, including fixation frequency and duration, the frequency, peak velocity, and amplitude of saccades, and phasic pupil diameter. Whereas most measures tended to change linearly along with decision certainty, pupil diameter revealed more nuanced and dynamic information about the time course of perceptual decision making. Together, results demonstrate robust alterations in eye movement behavior as a function of decision certainty and attention demands, and suggest that monitoring oculomotor variables during applied task performance may prove valuable for identifying and remediating transient states of uncertainty.



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Relative weighting of acoustic information during mating decisions in grasshoppers indicates signatures of sexual selection

Abstract

The decision with whom to mate is crucial in determining an individual's fitness and is often based on the evaluation of visual or acoustic displays produced during courtship. Accordingly, the algorithms for evaluating such courtship signals are shaped by sexual selection and should reflect the expected benefits and costs of mating: signals bearing heterospecific features should be rapidly rejected, since mating would produce no fertile offspring, while signals resembling conspecific ones should be weighted proportional to mate quality. We test these hypotheses in females of the grasshopper Chorthippus biguttulus who assess males by their song, which is produced as a sequence of subunits with species and individual specific signatures. We present mixed sequences of subunits with conflicting cues and use a computational model of decision-making to infer how sensory information is weighted and integrated over the song. Consistent with our hypothesis, females do weight sensory cues according to the expected fitness benefits/costs: heterospecific subunits are weighted particularly negatively and lead to a rejection of the male early in the song. Conspecific subunits are weighted moderately, permitting a more complete evaluation of the full song. However, there exists an overall negative bias against mating, possible causes of which are discussed.



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Higher levels of cardiorespiratory fitness keep liver mitochondria happy!

Abstract

The concept that regular physical activity (PA) and exercise training promotes mitochondrial biogenesis in skeletal muscle, enhancing mitochondrial quality and quantity and in doing so increasing oxidative phosphorylation capacity, has been well established for almost 50 years.

This article is protected by copyright. All rights reserved



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Risk of liver decompensation with cumulative use of mitochondrial toxic nucleoside analogues in HIV/hepatitis C virus coinfection

Pharmacoepidemiology and Drug Safety

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Long work hours tied to atrial fibrillation

Reuters Health News

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Ensuring early mobilization within an enhanced recovery program for colorectal surgery: a randomized controlled trial

Annals of Surgery

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Pressing questions about medical procedures aren’t getting attention: Reviewers

Reuters Health News

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Effects of antithrombotic therapy on bleeding after endoscopic submucosal dissection: A systematic review and meta-analysis

Gastrointestinal Endoscopy

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Inflammatory bowel disease and small bowel cancer risk, clinical characteristics, and histopathology- A population-based study

Clinical Gastroenterology and Hepatology

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Design and rationale for a real-world observational cohort of patients with nonalcoholic fatty liver disease: The TARGET-NASH study

Contemporary Clinical Trials

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Oncologic burden of HCV infection

CA: A Cancer Journal for Clinicians

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Dosimetric predictors for acute esophagitis during radiation therapy for lung cancer - results of a large statewide observational study

Practical Radiation Oncology

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Association between proton pump inhibitor use and cognitive function in women

Gastroenterology

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Chronic comorbidities associated with inflammatory bowel disease: Prevalence and impact on healthcare costs in Switzerland

European Journal of Gastroenterology & Hepatology

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Long-term response after stopping tenofovir disoproxil fumarate in non-cirrhotic HBeAg-negative patients - FINITE study

Journal of Hepatology

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Study finds slight autism risk link to antidepressants in pregnancy

Reuters Health News

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Effect of gluten-free diet on cerebellar MR spectroscopy in gluten ataxia

Neurology®

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Opioid-induced constipation relief of fixed-ratio combination prolonged-release oxycodone/naloxone compared with oxycodone and morphine for chronic non-malignant pain: A systematic review and meta-analysis of randomized controlled trials

Journal of Pain and Symptom Management

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Preperitoneal fat as a noninvsasive marker of increased risk of severe non-alcoholic fatty liver disease in patients with type 2 diabetes

Journal of Gastroenterology and Hepatology

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Validation of whole-slide imaging in the primary diagnosis of liver biopsies in a university hospital

Digestive and Liver Diseases

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Predictors of esophageal varices and first variceal bleeding in liver cirrhosis patients

World Journal of Gastroenterology

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Nonalcoholic fatty liver disease can be predicted by retinal vascular changes in patients with obesity without hypertension or diabetes

European Journal of Gastroenterology & Hepatology

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Directly observed therapy of sofosbuvir/ribavirin +/- peginterferon with minimal monitoring for the treatment of chronic hepatitis C in people with a history of drug use in Chennai, India (C-DOT)

Journal of Viral Hepatitis

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Blunted cerebral vascular responsiveness to hypercapnia in obese individuals

Abstract

Obesity increases the risk of cardiovascular disease (CVD) by more than 45%. Furthermore, obesity is a contributing factor for cognitive impairment and Alzheimer disease. The mechanisms accounting for this increased disease risk have not been clarified. This study tested the hypothesis that the total range of change (a) in cerebral blood velocity (CBV) and cerebral vascular conductance (CVCI) as well as maximum (y0) CBV and CVCI achieved during rebreathing-induced hypercapnia would be attenuated in obese individuals (obese). 16 lean and 15 obese individuals participated. The magnitude of rebreathing-induced hypercapnia was similar between groups (Lean: ∆ 15 ± 3 mmHg vs. Obese ∆ 15 ± 2 mmHg; = 0.82). The total range of change in CBV during rebreathing (a; percentage) was similar between groups (Lean: 91 ± 24 % vs. Obese: 76 ± 19 %, = 0.07) whereas the total range of change in CVCI during rebreathing (a; percentage) was attenuated in the Obese (Lean: 71 ± 20 % vs. Obese: 51 ± 15 %, P < 0.01). Likewise, the maximal increase in CBV during rebreathing (y0; percentage) was similar between groups (Lean: 189 ± 22 % vs. Obese: 179 ± 20 %, = 0.20) whereas the maximal increase in CVCI during rebreathing (y0; percentage) was attenuated in the Obese (Lean: 172 ± 19 % vs. Obese: 155 ± 17 %, = 0.01). These data indicate that cerebral vascular response to rebreathing-induced hypercapnia is attenuated in obese individuals. This impairment may be a contributing factor for the elevated cerebral vascular / neurocognitive disease risk in this population.

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Replication confirms the association of loci in FOXE1, PDE8B, CAPZB and PDE10A with thyroid traits: a Genetics of Diabetes Audit and Research Tayside study.

Objective: Replication of associations in genome-wide association studies is desirable to ensure that such signals are potentially clinically meaningful. This study aimed to replicate associations of selected single-nucleotide polymorphisms (SNPs) with hypothyroidism and serum thyroid-stimulating hormone (TSH) using electronic medical records (EMRs). Patients and methods: A cross-sectional study was carried out among patients of European Caucasian ethnicity from the Genetics of Diabetes Audit and Research Tayside recruited in Tayside (Scotland, UK). EMRs (biochemistry, prescribing, hospital admissions and demographics) were used to ascertain patients with hypothyroidism and their controls as well as average serum TSH concentration, and linked to genetic biobank data. Genetic tests of association were performed using logistic and linear regression models. Results: We analysed 1703 cases of hypothyroidism and 9457 controls. All four SNPs located on chromosome 9 at FOXE1 were associated with hypothyroidism with similar effect estimates (odds ratio=0.75-0.76, P

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