bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) Fellowship Program Website Content and Quality
Authors: Homer Natalie , Yoon Michael K.
Published: December 2016

Purpose:

The qualities that applicants value in the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) fellowship programs have been studied, but the availability of this information on program websites has not yet been reviewed. The authors evaluated the availability of resident-valued ASOPRS fellowship program information on the Internet.

Methods:

The authors performed an Internet search of the 53 ASOPRS fellowship program websites and evaluated websites for 20 characteristics of interest to ASOPRS fellowship applicants such as teaching faculty, program description, rotation schedule, operative cases, and interview information.

Results:

Of the 53 ASOPRS fellowship programs, 43 (81.1%) had a fellowship program-dedicated website. The fellowship websites contained a mean 7.6 characteristics (38.1%, range 0–15). Faculty listing, program description, and case diversity were the most commonly included data (74.4%, 72.1%, and 69.8%, respectively). Fellow selection process, interview information, and graduate job placement were least commonly included (7.0%, 2.3%, and 0.0%, respectively). There was no significant difference in website inclusiveness based on fellowship region or faculty number. Programs affiliated with an ophthalmology residency were more complete than those that were not (40.3% vs. 20.0%, p = 0.0098).

Conclusions:

This review found that most programs had websites and contained a reasonable number of characteristics. However, applicant-valued information regarding surgical volume, procedure variety, application information, and postgraduate employment history were often missing. American Society of Ophthalmic Plastic and Reconstructive Surgery fellowship programs may improve match outcomes by providing and enhancing program websites with details that their applicants seek.
Incident and long-term opioid therapy among patients with psychiatric conditions and medications: a national study of commercial health care claims
Authors: Quinn Patrick D. , Hur Kwan , Chang Zheng , Krebs Erin E. , Bair Matthew J. , Scott Eric L. , Rickert Martin E. , Gibbons Robert D. , Kroenke Kurt , D'Onofrio Brian M.
Published: December 2016

There is growing evidence that opioid prescribing in the United States follows a pattern in which patients who are at the highest risk of adverse outcomes from opioids are more likely to receive long-term opioid therapy. These patients include, in particular, those with substance use disorders (SUDs) and other psychiatric conditions. This study examined health insurance claims among 10,311,961 patients who filled prescriptions for opioids. Specifically, we evaluated how opioid receipt differed among patients with and without a wide range of preexisting psychiatric and behavioral conditions (ie, opioid and nonopioid SUDs, suicide attempts or other self-injury, motor vehicle crashes, and depressive, anxiety, and sleep disorders) and psychoactive medications (ie, antidepressants, benzodiazepines, hypnotics, mood stabilizers, antipsychotics, and medications used for SUD, tobacco cessation, and attention-deficit/hyperactivity disorder). Relative to those without, patients with all assessed psychiatric conditions and medications had modestly greater odds of subsequently filling prescriptions for opioids and, in particular, substantially greater risk of long-term opioid receipt. Increases in risk for long-term opioid receipt in adjusted Cox regressions ranged from approximately 1.5-fold for prior attention-deficit/hyperactivity disorder medication prescriptions (hazard ratio [HR] = 1.53; 95% confidence interval [CI], 1.48-1.58) to approximately 3-fold for prior nonopioid SUD diagnoses (HR = 3.15; 95% CI, 3.06-3.24) and nearly 9-fold for prior opioid use disorder diagnoses (HR = 8.70; 95% CI, 8.20-9.24). In sum, we found evidence of greater opioid receipt among commercially insured patients with a breadth of psychiatric conditions. Future studies assessing behavioral outcomes associated with opioid prescribing should consider preexisting psychiatric conditions.
Brain activity for tactile allodynia: a longitudinal awake rat functional magnetic resonance imaging study tracking emergence of neuropathic pain
Authors: Chang Pei-Ching , Centeno Maria Virginia , Procissi Daniel , Baria Alex , Apkarian A. Vania
Published: December 2016

Tactile allodynia, a condition in which innocuous mechanical stimuli are perceived as painful, is a common feature of chronic pain. However, how the brain reorganizes in relation to the emergence of tactile allodynia is still largely unknown. This may stem from the fact that experiments in humans are cross-sectional in nature, whereas animal brain imaging studies typically require anaesthesia rendering the brain incapable of consciously sensing or responding to pain. In this longitudinal functional magnetic resonance imaging study in awake rats, we tracked brain activity with the development of tactile allodynia. Before injury, innocuous air-puff stimuli evoked a distributed sensory network of activations, including contralateral somatosensory cortices, thalamus, insula, and cingulate cortex. Moreover, the primary somatosensory cortex displayed a graded response tracking air-puff stimulus intensities. After neuropathic injury, and for stimuli in which the intensity exceeded the paw withdrawal threshold (evoking tactile allodynia), the blood oxygenation level-dependent response in the primary somatosensory cortex was equivalent to that evoked by the identical stimulus before injury. In contrast, nucleus accumbens and prefrontal brain areas displayed abnormal activity to normally innocuous stimuli when such stimuli induced tactile allodynia at 28 days after peripheral nerve injury, which had not been the case at 5 days after injury. Our data indicate that tactile allodynia-related nociceptive inputs are not observable in the primary somatosensory cortex BOLD response. Instead, our data suggest that, in time, tactile allodynia differentially engages neural circuits that regulate the affective and motivational components of pain.
Sex differences in the efficacy of psychological therapies for the management of chronic and recurrent pain in children and adolescents: a systematic review and meta-analysis
Authors: Boerner Katelynn E. , Eccleston Christopher , Chambers Christine T. , Keogh Edmund
Published: December 2016

Sex differences in chronic pain are reported to emerge during adolescence, although it is unclear if this includes responses to treatment. We conducted a meta-analysis to examine whether sex differences were present on outcome variables at pretreatment and whether the efficacy of psychological therapies for pediatric chronic pain differs between boys and girls at posttreatment and follow-up time points. Searches were conducted, extending 2 existing Cochrane reviews of randomized controlled trials examining the efficacy of psychological therapies for chronic and recurrent pain in children and adolescents. Forty-six articles were eligible for inclusion, and data were extracted regarding pain, disability, anxiety, and depression in boys and girls at pretreatment, posttreatment, and follow-up time points. No published study reported outcome data separately by sex, so authors of all studies were contacted and 17 studies provided data. Twice as many girls (n = 1760) were enrolled into clinical trials of psychological therapies for pediatric chronic pain than boys (n = 828). Girls reported higher depression and anxiety at pretreatment than boys. Girls with headache also reported significantly greater pretreatment pain severity. Treatment gains were consistent across the sexes. One exception was for posttreatment disability in children with nonheadache pain conditions; girls exhibited a significant effect of treatment relative to control condition (standardized mean difference = −0.50 [−0.80, −0.20], P < 0.01), but no such effect was observed for boys (standardized mean difference = −0.08 [−0.44, 0.28], P = 0.66). Future research should examine whether mechanisms of treatment efficacy differ between boys and girls and consider the impact of pretreatment sex differences on response to treatment.
Defining Entry-Level Practice in Acute Care Physical Therapist Practice
Authors: Greenwood Kristin , Stewart Eric , Hake Melissa , Milton Erin , Mitchell Lauren , Sanders Babette
Published: December 2016

Background and Purpose:

The requirements of an entry-level physical therapist to practice in acute care are not well defined. The Academy of Acute Care Physical Therapy convened the Minimum Skills Task Force to define entry-level practice in acute care. The purpose of this report is to discuss the process and outcome of the development of the Core Competencies for Entry-level Practice in Acute Care Physical Therapy.

Methods:

A task force of acute care clinicians and educators was assembled to develop this document. This document was created through a multistep process consisting of a review of limited existing literature and educational documents, reviews from 4 physical therapists with extensive specialized expertise in acute care physical therapy, and solicitation of Academy of Acute Care Physical Therapy member feedback through 2 webinar forums.

Results:

The final document was adopted by the Academy of Acute Care Physical Therapy in December 2015. The Core Competencies for Entry-Level Practice in Acute Care Physical Therapy identifies the necessary knowledge, actions, and behaviors that are required of an entry-level clinician in the acute care environment.

Conclusion:

The task force charged with the process and creation of the Core Competencies for Entry-Level Practice in Acute Care Physical Therapy met the challenge of integrating best available research, clinical experience, member feedback of all levels of experience, and expert feedback to develop this document. Further research on the benefits of this document to guide preparation for the entry-level clinician is needed.
Vitamin C Deficiency, High-Sensitivity C-Reactive Protein, and Cardiac Event-Free Survival in Patients With Heart Failure
Authors: Song Eun Kyeung , Kang Seok-Min
Published: December 2016

Background:

Vitamin C is related to lower levels of high-sensitivity C-reactive protein (hsCRP), an inflammatory biomarker that predicts cardiovascular disease. Whether vitamin C deficiency is associated with hsCRP and cardiac events in heart failure (HF) patients has not been examined.

Purpose:

The aim of this study is to determine the relationships among vitamin C intake, serum levels of hsCRP, and cardiac events.

Methods:

A total of 200 HF patients completed a 3-day food diary to determine vitamin C deficiency and provided blood to measure serum levels of hsCRP. Patients were followed for 2 years to obtain data on cardiac event-free survival. Moderation analyses with hierarchical logistic and Cox regressions were used for the data analysis.

Results:

Seventy-eight patients (39%) had vitamin C deficiency and 100 (50%) had an hsCRP level higher than 3 mg/L. Vitamin C deficiency was associated with an hsCRP level higher than 3 mg/L in the hierarchical logistic regression (odds ratio, 2.40; 95% confidence interval, [1.13–5.10]; P = .023). Vitamin C deficiency (hazard ratio, 1.68; 95% CI, 1.05–2.69, P = .029) and hsCRP level higher than 3 mg/L (hazard ratio, 1.79; 95% CI, 1.07–3.01; P = .027) predicted shorter cardiac event-free survival in hierarchical Cox regression. The interaction of hsCRP level higher than 3 mg/L and vitamin C deficiency produced a 2.3-fold higher risk for cardiac events (P = .002) in moderation analysis. Higher level of hsCRP predicted shorter cardiac event-free survival only in patients with vitamin C deficiency (P = .027), but not in those with vitamin C adequacy.

Conclusion:

Vitamin C deficiency moderated the relationship between inflammation and cardiac events in patients with HF. Future study is required to determine whether adequate intake of vitamin C could play a protective role against the impact of inflammation on cardiac events in HF patients.
Sex Differences in the Effect of Atomoxetine on the QT Interval in Adult Patients With Attention-Deficit Hyperactivity Disorder
Authors: Suzuki Yutaro , Tajiri Misuzu , Sugimoto Atsunori , Orime Naoki , Hayashi Taketsugu , Egawa Jun , Sugai Takuro , Inoue Yoshimasa , Someya Toshiyuki
Published: December 2016

Background

The effects of atomoxetine on QT in adults remain unclear. In this study, we examined whether the use of atomoxetine to treat attention-deficit hyperactivity disorder in adults is associated with QT prolongation.

Methods

Forty-one subjects with attention-deficit hyperactivity disorder were enrolled in this study. Participants were administered 40, 80, or 120 mg atomoxetine daily and were maintained on their respective dose for at least 2 weeks. We conducted electrocardiographic measurements and blood tests, measuring plasma atomoxetine concentrations after treatment. Electrocardiograms of 24 of the patients were also obtained before atomoxetine treatment. The QT interval was corrected using Bazett (QTcB) and Fridericia (QTcF) correction formulas.

Results

In these 24 patients, only the female patients had prolonged QTcB (P= 0.039) after atomoxetine treatment. There was no correlation between plasma atomoxetine concentrations and the corrected QT interval (QTc), or between atomoxetine dosage and the QTc. However, in female patients, there was a significant positive correlation between atomoxetine dosage and the QTcB (r= 0.631,P= 0.012), and there was a marginally significant positive correlation between atomoxetine dosage and the QTcF (r= 0.504,P= 0.055). In male patients, there was no correlation between atomoxetine dosage and the QTcB or QTcF intervals. There was no correlation between plasma atomoxetine concentrations and the QTc in either female or male patients.

Implications

Clinicians should exhibit caution when prescribing atomoxetine, particularly for female patients.
Hippocrates Quoted “If an Empyema Does Not Rupture, Death Will Occur”
Authors: Hardavella Georgia , Papakonstantinou Nikolaos A. , Karampinis Ioannis , Papavasileiou Gerasimos , Ajab Shereen , Shafaat Mohammed , Malagaris Stavros , Anastasiou Nikolaos
Published: December 2016

Background:

The aim of this study was to evaluate the safety and efficacy of medical thoracoscopy through a single port [single-port medical thoracoscopy (S-MT)] for the treatment of empyema thoracis in its early stages.

Methods:

We performed a retrospective analysis reviewing the medical records of 84 patients referred for empyema and treated by medical thoracoscopy at our Thoracic Departments from January 2001 until November 2014. S-MT was performed under local anesthesia with neuroleptoanalgesia and spontaneous breathing using a single 1-cm incision for debridement and lavage of the pleural cavity.

Results:

A total of 84 patients underwent S-MT for pleural empyema stage I (9 patients, 10.7%) or II (75 patients, 89.3%). Median age was 61.8 years (range, 18 to 84 y). Male to female ratio was 3.76. Surgery was performed 5 to 26 days after the onset of symptoms. Macroscopically complete debridement of the pleural cavity was achieved in 71 patients (84.5% of cases). The rest 15.5% of cases required video-assisted thoracoscopic surgery or open decortication due to trapped-lung syndrome. Median operation time was 45 minutes (range, 30 to 94 min). No intraoperative complications occurred. In-hospital mortality was zero, whereas in-hospital morbidity rate was 16.7%. Median hospital stay was 7.8 days (range, 3 to 18 days). Recurrence rate was 4.8% as 4 patients experienced a relapse of empyema.

Conclusion:

It seems that S-MT is a minimally invasive, safe and effective procedure for the treatment of pleural empyema with very good results in early stages of the disease and reduced time of hospital stay.
Low Accuracy of the HeartMate Risk Score for Predicting Mortality Using the INTERMACS Registry Data
Authors: Kanwar Manreet K. , Lohmueller Lisa C. , Kormos Robert L. , Loghmanpour Natasha A. , Benza Raymond L. , Mentz Robert J. , Bailey Stephen H. , Murali Srinivas , Antaki James F.
Published: December 2016

Selection is a key determinant of clinical outcomes after left ventricular assist device (LVAD) placement in patients with end-stage heart failure. The HeartMate II risk score (HMRS) has been proposed to facilitate risk stratification and patient selection for continuous flow pumps. This study retrospectively assessed the performance of HMRS in predicting 90 day and 1 year mortality in patients within the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). A total of 11,523 INTERMACS patients who received a continuous flow LVAD between 2010 and 2015 were retrospectively categorized per their calculated HMRS to predict their 90 day and 1 year risk of mortality. The performance of the score was evaluated by the area under curve (AUC) of the receiver operator characteristic. We also performed multiple regression analysis using variables from the HMRS calculation on the INTERMACS data. The HMRS model showed moderate discrimination for both 90 day and 1 year mortality prediction with AUCs of 61% and 59%, respectively. The predictions had similar accuracy irrespective of whether the pump was axial or centrifugal flow. Multivariable analysis using independent variables used in the original HMRS analysis revealed different set of variables to be predictive of 90 day mortality than those used to calculate HMRS. HMRS predicts both 90 day and 1 year mortality with poor discrimination when applied to a large cohort of LVAD patients. Newer risk prediction models are therefore needed to optimize the therapeutic application of LVAD therapy. Patient selection for appropriate use of LVADs is critical. Currently available risk stratification tools (HMRS) continue to be limited in their ability to accurately predict mortality after LVAD. This study highlights these limitations when applied to a large, comprehensive, multicenter database. HMRS predicts mortality with only modest discrimination when applied to a large cohort of LVAD patients. Better risk stratification tools are needed to optimize outcomes.
Efficacy of Subcutaneous Electrocardiogram Leads for Synchronous Timing During Chronic Counterpulsation Therapy
Authors: Carnahan Stephen R. , Koenig Steven C. , Sobieski Michael A. , Schumer Erin M. , Monreal Gretel , Wang Yu , Choi Young , Meuris Brek J. , Tompkins Landon H. , Wu Zhongjun J. , Slaughter Mark S. , Giridharan Guruprasad A.
Published: December 2016

Counterpulsation devices (CPDs) require an accurate, reliable electrocardiogram (ECG) waveform for triggering inflation and deflation. Surface electrodes are for short-term use, and transvenous/epicardial leads require invasive implant procedure. A subcutaneous ECG lead configuration was developed as an alternative approach for long-term use with timing mechanical circulatory support (MCS) devices. In this study, efficacy testing was completed by simultaneously recording ECG waveforms from clinical-grade epicardial (control) and subcutaneous (test) leads in chronic ischemic heart failure calves implanted with CPD for up to 30 days. Sensitivity and specificity of CPD triggering by R-wave detection was quantified for each lead configuration. The subcutaneous leads provided 98.9% positive predictive value and 98.9% sensitivity compared to the epicardial ECG leads. Lead migration (n = 1) and fracture (n = 1) were observed in only 2 of 40 implanted leads, without adversely impacting triggering efficacy due to lead redundancy. These findings demonstrate the efficacy of subcutaneous ECG leads for long-term CPD timing and potential use as an alternative method for MCS device timing.
C-reactive protein-to-albumin ratio is a predictor of hepatitis B virus related decompensated cirrhosis: time-dependent receiver operating characteristics and decision curve analysis
Authors: Huang Si-Si , Xie Dong-Mei , Cai Yi-Jing , Wu Jian-Min , Chen Rui-Chong , Wang Xiao-Dong , Song Mei , Zheng Ming-Hua , Wang Yu-Qun , Lin Zhuo , Shi Ke-Qing
Published: December 2016

Background and aims

Hepatitis B virus (HBV) infection remains a major health problem and HBV-related-decompensated cirrhosis (HBV-DC) usually leads to a poor prognosis. Our aim was to determine the utility of inflammatory biomarkers in predicting mortality of HBV-DC.

Materials and methods

A total of 329 HBV-DC patients were enrolled. Survival estimates for the entire study population were generated using the Kaplan–Meier method. The prognostic values for model for end-stage liver disease (MELD) score, Child–Pugh score, and inflammatory biomarkers neutrophil/lymphocyte ratio, C-reactive protein-to-albumin ratio (CAR), and lymphocyte-to-monocyte ratio (LMR) for HBV-DC were compared using time-dependent receiver operating characteristic curves and time-dependent decision curves.

Results

The survival time was 23.1±15.8 months. Multivariate analysis identified age, CAR, LMR, and platelet count as prognostic independent risk factors. Kaplan–Meier analysis indicated that CAR of at least 1.0 (hazard ratio, 7.19; 95% confidence interval, 4.69–11.03), and LMR less than 1.9 (hazard ratio, 2.40; 95% confidence interval, 1.69–3.41) were independently associated with mortality of HBV-DC. The time-dependent receiver operating characteristic indicated that CAR showed the best performance in predicting mortality of HBV-DC compared with LMR, MELD score, and Child–Pugh score. The results were also confirmed by time-dependent decision curves.

Conclusion

CAR and LMR were associated with the prognosis of HBV-DC. CAR was superior to LMR, MELD score, and Child–Pugh score in HBV-DC mortality prediction.
An Examination of Claims-based Predictors of Overdose from a Large Medicaid Program
Authors: Cochran Gerald , Gordon Adam J. , Lo-Ciganic Wei-Hsuan , Gellad Walid F. , Frazier Winfred , Lobo Carroline , Chang Chung-Chou H. , Zheng Ping , Donohue Julie M.
Published: December 2016

Background:

Health systems may play an important role in identification of patients at-risk of opioid medication overdose. However, standard measures for identifying overdose risk in administrative data do not exist.

Objective:

Examine the association between opioid medication overdose and 2 validated measures of nonmedical use of prescription opioids within claims data.

Research Design:

A longitudinal retrospective cohort study that estimated associations between overdose and nonmedical use.

Subjects:

Adult Pennsylvania Medicaid program 2007–2012 patients initiating opioid treatment who were: nondual eligible, without cancer diagnosis, and not in long-term care facilities or receiving hospice.

Measures:

Overdose (International Classification of Disease, ninth edition, prescription opioid poisonings codes), opioid abuse (opioid use disorder diagnosis while possessing an opioid prescription), opioid misuse (a composite indicator of number of opioid prescribers, number of pharmacies, and days supplied), and dose exposure during opioid treatment episodes.

Results:

A total of 372,347 Medicaid enrollees with 583,013 new opioid treatment episodes were included in the cohort. Opioid overdose was higher among those with abuse (1.5%) compared with those without (0.2%, P<0.001). Overdose was higher among those with probable (1.8%) and possible (0.9%) misuse compared with those without (0.2%, P<0.001). Abuse [adjusted rate ratio (ARR), 1.52; 95% confidence interval (CI), 1.10–2.10), probable misuse (ARR, 1.98; 95% CI, 1.46–2.67), and possible misuse (ARR, 1.76; 95% CI, 1.48–2.09) were associated with significantly more events of opioid medication overdose compared with those without.

Conclusions:

Claims-based measures can be used by health systems to identify individuals at-risk of overdose who can be targeted for restrictions on opioid prescribing, dispensing, or referral to treatment.
State-Level Surveillance of Underinsurance and Health Care-Related Financial Burden
Authors: Dumont Dora M. , Oh Junhie , Cooper Tara
Published: December 2016

Background:

The Affordable Care Act (ACA) has reduced uninsurance, but underinsurance, health care-related financial burden, and dental uninsurance may not follow suit. Underinsurance is associated with reduced access to care, household debt, and bankruptcy but has been difficult to track without economic data.

Methods:

We used readily available state-level survey data to build a model that states can adopt to implement surveillance over underinsurance and health care-related financial burden, as well as assess related disparities and health profiles.

Results:

The state prevalence of underinsurance and dental uninsurance did not change in the first year of the ACA's individual mandate. Underinsurance was associated with poorer health-related quality-of-life measures: compared with the fully insured, underinsured adults had an adjusted odds ratio of 2.40 (95% CI, 1.71-3.38) of fair or poor general health.

Conclusion:

Tracking underinsurance and medical debt can help public health and health care access stakeholders evaluate which mechanisms (deductibles, co-pays, uncovered services, or is proportionately priced health care services and products) are barriers to care and improved health outcomes.
Bacterial pneumonia as an influenza complication
Authors: Martin-Loeches Ignacio , van Someren Gréve Frank , Schultz Marcus J.
Published: December 2016

Purpose of review

The pathogenesis and impact of coinfection, in particular bacterial coinfection, in influenza are incompletely understood. This review summarizes results from studies on bacterial coinfection in the recent pandemic influenza outbreak.

Recent findings

Systemic immune mechanisms play a key role in the development of coinfection based on the complexity of the interaction of the host and the viral and bacterial pathogens. Several studies were performed to determine the point prevalence of bacterial coinfection in influenza. Coinfection in influenza is frequent in critically ill patients with Streptococcus pneumoniae being the most frequent bacterial pathogen and higher rates of potentially resistant pathogens over the years.

Bacterial pneumonia is certainly an influenza complication. The recent epidemiology findings have helped to partially resolve the contribution of different pathogens. Immunosuppression is a risk factor for bacterial coinfection in influenza, and the epidemiology of coinfection has changed over the years during the last influenza pandemic, and these recent findings should be taken into account during present outbreaks.
Diffusion-Weighted Imaging for Differentiating Uterine Leiomyosarcoma From Degenerated Leiomyoma
Authors: Li Hai Ming , Liu Jia , Qiang Jin Wei , Zhang Hao , Zhang Guo Fu , Ma FengHua
Published: December 2016

Purpose

The study aimed to investigate magnetic resonance diffusion-weighted imaging (DWI) in the differentiation of uterine leiomyosarcoma (ULMS) from degenerated leiomyoma (DLM).

Methods

Sixteen patients with ULMSs and 26 patients with DLMs confirmed by surgery and pathology underwent conventional magnetic resonance imaging and DWI. The mean apparent diffusion coefficient (ADC) values of the 2 groups’ tumors were measured and compared using an independent-sample t test (b = 0.1000 s/mm2 [ADC1]; b = 0.800 s/mm2 [ADC2], respectively). A receiver operating characteristic curve was used to evaluate the diagnostic performance of DWI in the differentiation of ULMS from DLM. Intraobserver and interobserver agreements were evaluated using an intraclass correlation coefficient and Bland-Altman analysis.

Results

The mean ADC value in ULMSs (0.81 ± 0.14 × 10−3mm2/s [ADC1], 0.90 ± 0.11 × 10−3mm2/s [ADC2]) was significantly lower than that in DLMs (1.22 ± 0.22 × 10−3mm2/s [ADC1], 1.50 ± 0.22 × 10−3mm2/s [ADC2]) (P < 0.001, <0.001, respectively). The sensitivity, specificity, accuracy, and positive and negative predictive values for characterizing ULMS were 100%, 90%, 93%, and 83% and 100% [ADC1] and 100%, 93%, 96%, and 90% and 100% [ADC2]; respectively. Intraobserver and interobserver reproducibilities were excellent (intraclass correlation coefficient = 0.967–0.988; small variability and 95% limits of agreement).

Conclusions

Diffusion-weighted imaging is helpful in differentiating ULMS from DLM.
Etiology of Shock in the Emergency Department: A 12-Year Population-Based Cohort Study
Authors: Gitz Holler Jon , Jensen Helene Kildegaard , Henriksen Daniel Pilsgaard , Rasmussen Lars Melholt , Mikkelsen Søren , Pedersen Court , Lassen Annmarie Touborg
Published: December 2016

Introduction:

The knowledge of the etiology and associated mortality of undifferentiated shock in the emergency department (ED) is limited. We aimed to describe the etiology-based proportions and incidence rates (IR) of shock, as well as the associated mortality in the ED.

Methods:

Population-based cohort study at a University Hospital ED in Denmark from January 1, 2000, to December 31, 2011. Patients aged ≥18 years living in the ED-catchment area (N = 225,000) with a first-time ED presentation with shock (n = 1,553) defined as hypotension (systolic blood pressure ≤100 mm Hg) and ≥1 organ failures were included. Discharge diagnoses defined the etiology and were grouped as follows: distributive septic shock (SS), distributive non-septic shock (NS), cardiogenic shock (CS), hypovolemic shock (HS), obstructive shock (OS), and other conditions (OC). Outcomes were etiology-based characteristics, annual IR per 100,000 person-years at risk (95% confidence intervals [CIs]), mortality at 0 to 7-, and 0 to 90 days (95% CIs) and hazard rates (HR) at 0 to 7, 8 to 90 days (95% CIs). Poisson and Cox regression models were used for analyses.

Results:

Among 1,553 shock patients: 423 (27.2%) had SS, 363 (23.4%) NS, 217 (14.0%) CS, 479 (30.8%) HS, 14 (0.9%) OS, and 57 (3.7%) OC. The corresponding IRs were 16.2/100,000 (95% CI: 14.8–17.9), 13.9/100,000 (95% CI: 12.6–15.4), 8.3/100,000 (95% CI: 7.3–9.5), 18.4/100,000 (95% CI: 16.8–20.1), 0.5/100,000 (95% CI: 0.3–0.9), and 2.2/100,000 (95% CI: 1.7–2.8). SS IR increased from 8.4 to 28.5/100,000 during the period 2000 to 2011. Accordingly, the 7-, and 90-day mortalities of SS, NS, CS, and HS were 30.3% (95% CI: 25.9–34.7) and 56.2% (95% CI: 50.7–61.5), 12.7% (95% CI: 9.2–16.1) and 22.6% (95% CI: 18.1–27.7), 34.6% (95% CI: 28.2–40.9) and 52.3% (95% CI: 44.6–59.8), 19.2% (95% CI: 15.7–22.7), and 36.8% (95% CI: 33.3–43.3). SS (HR = 1.46 [95% CI: 1.03–2.07]), and CS (HR = 2.15 [95% CI: 1.47–3.13]) were independent predictors of death within 0 to 7 days, whereas SS was a predictor within 8 to 90 days (HR = 1.66 [95% CI: 1.14–2.42]).

Conclusion:

HS and SS are frequent etiological characteristics followed by NS and CS, whereas OS is a rare condition. We confirm the increasing trend of SS, as previously reported. Seven-day mortality ranged from 12.7% to 34.6%, while 90-day mortality ranged from 22.6% to 56.2%. The underlying etiology was an independent predictor of mortality.
Palliative care in pulmonary arterial hypertension
Authors: Gin-Sing Wendy
Published: December 2016

Purpose of review

Developments in the management of pulmonary arterial hypertension have significantly improved prognosis changing this from an acute to a chronic disease. Despite optimal treatment many patients still have a high-symptom burden both because of the disease and the side-effects of therapy, consequently there is an increasing need for a palliative care approach to improve the quality of life for this patient group. This review article will outline the need for palliative care support for patients with pulmonary arterial hypertension, discuss the barriers that currently exist and suggest how this may be improved.

Recent findings

Studies have been conducted which explore the role of palliative care in pulmonary arterial hypertension including physicians attitudes and the current barriers that exist to prevent its implementation.

Specialist palliative support is utilized in the minority of patients with pulmonary arterial hypertension despite a need for symptom control. Patients may benefit from the introduction of a palliative care approach as part of their standard care, but to achieve this there needs to be a greater understanding of the role of palliative care by both clinicians and patients and more research into the benefits for patients with pulmonary arterial hypertension.
A statistical test on single-cell data reveals widespread recurrent mutations in tumor evolution
Authors: Kuipers Jack , Jahn Katharina , Raphael Benjamin J. , Beerenwinkel Niko
Published: December 2016

The infinite sites assumption, which states that every genomic position mutates at most once over the lifetime of a tumor, is central to current approaches for reconstructing mutation histories of tumors, but has never been tested explicitly. We developed a rigorous statistical framework to test the assumption with single-cell sequencing data. The framework accounts for the high noise and contamination present in such data. We found strong evidence for recurrent mutations at the same site in 8 out of 9 single-cell sequencing datasets from human tumors. Six cases involved the loss of earlier mutations, five of which occurred at sites unaffected by large scale genomic deletions. Two cases exhibited parallel mutation, including the dataset with the strongest evidence of recurrence. Our results refute the general validity of the infinite sites assumption and indicate that more complex models are needed to adequately quantify intra-tumor heterogeneity.
Opposing transcriptional mechanisms regulateToxoplasmadevelopment
Authors: Hong Dong-Pyo , Radke Joshua B. , White Michael W.
Published: December 2016

TheToxoplasmabiology that underlies human chronic infection is developmental conversion of the acute tachyzoite stage into the latent bradyzoite stage. We investigated the role of two alkaline-stress induced ApiAP2 transcription factors, AP2IV-3 and AP2IX-9, in bradyzoite development. These factors were expressed in two overlapping waves during bradyzoite development with AP2IX-9 increasing expression earlier than AP2IV-3, which peaked as AP2IX-9 expression was declining. Disruption of the AP2IX-9 gene enhanced, while deletion of AP2IV-3 gene decreased tissue cyst formation demonstrating these factors have opposite functions in bradyzoite development. Conversely, conditional overexpression of FKBP-modified of AP2IX-9 or AP2IV-3 with the small molecule Shield 1 had a reciprocal effect on tissue cyst formation confirming the conclusions of the knockout experiments. The AP2IX-9 repressor and AP2IV-3 activator tissue cyst phenotypes were borne out in gene expression studies that determined many of the same bradyzoite genes were regulated in an opposite manner by these transcription factors. A common gene target was the canonical bradyzoite marker, BAG1, and mechanistic experiments determined that like AP2IX-9, AP2IV-3 regulates a BAG1 promoter-luciferase reporter and specific binds the BAG1 promoter in parasite chromatin. Altogether, these results suggest the AP2IX-9 transcriptional repressor and AP2IV-3 transcriptional activator likely compete to control bradyzoite gene expression, which may permitToxoplasmato better adapt to different tissue environments and select a suitable host cell for long term survival of the dormant tissue cyst.

IMPORTANCE

Toxoplasmainfections are life-long due to the development of the bradyzoite tissue cyst, which is effectively invisible to the immune system. Despite the important clinical consequences of this developmental pathway, the molecular basis of the switch mechanisms that control formation of the tissue cyst is still poorly understood. Significant changes in gene expression are associated with tissue cyst development and ApiAP2 transcription factors are an important mechanism regulating this developmental transcriptome. However, the molecular composition of these ApiAP2 mechanisms are not well defined and the operating principles of ApiAP2 mechanisms are poorly understood. Here we establish that competing ApiAP2 transcriptional mechanisms operate to regulate this clinically important developmental pathway.
Using reference-free compressed data structures to analyze sequencing reads from thousands of human genomes
Authors: Dolle Dirk D. , Liu Zhicheng , Cotten Matthew , Simpson Jared T. , Iqbal Zamin , Durbin Richard , McCarthy Shane A. , Keane Thomas M.
Published: December 2016

We are rapidly approaching the point where we have sequenced millions of human genomes. There is a pressing need for new data structures to store raw sequencing data and efficient algorithms for population scale analysis. Current reference-based data formats do not fully exploit the redundancy in population sequencing nor take advantage of shared genetic variation. In recent years, the Burrows–Wheeler transform (BWT) and FM-index have been widely employed as a full-text searchable index for read alignment and de novo assembly. We introduce the concept of a population BWT and use it to store and index the sequencing reads of 2705 samples from the 1000 Genomes Project. A key feature is that, as more genomes are added, identical read sequences are increasingly observed, and compression becomes more efficient. We assess the support in the 1000 Genomes read data for every base position of two human reference assembly versions, identifying that 3.2 Mbp with population support was lost in the transition from GRCh37 with 13.7 Mbp added to GRCh38. We show that the vast majority of variant alleles can be uniquely described by overlapping 31-mers and show how rapid and accurate SNP and indel genotyping can be carried out across the genomes in the population BWT. We use the population BWT to carry out nonreference queries to search for the presence of all known viral genomes and discover human T-lymphotropic virus 1 integrations in six samples in a recognized epidemiological distribution.
Aggressive behaviours track transitions in seasonal phenotypes of female Siberian hamsters
Authors: Rendon Nikki M. , Amez Andrea C. , Proffitt Melissa R. , Bauserman Elizabeth R. , Demas Gregory E.
Published: December 2016

Seasonally breeding animals exhibit profound physiological and behavioural responses to changes in ambient day length (photoperiod), including changes in reproductive function and territorial aggression.

Species where aggression persists when gonads are regressed and circulating levels of gonadal hormones are low, such as Siberian hamsters (Phodopus sungorus) and song sparrows (Melospiza melodia), challenge the well‐established framework that gonadal hormones are important mediators of aggression.

A solution to this apparent paradox is that a season‐specific increase in sensitivity to hormones in brain areas associated with aggression offsets low gonadal hormone levels during periods of reproductive quiescence.

To test this hypothesis, we manipulated photoperiod to induce natural fluctuations in seasonal phenotype across multiple stages of the annual reproductive cycle in female Siberian hamsters that display increased aggression during short‐day reproductive quiescence, suggesting that behaviour persists independent of gonadal steroids.

Females were housed in long ‘summer’ days or short ‘winter’ days for 10, 24 or 30 weeks to capture gonadal regression, a transition back to a reproductively functional state and full gonadal recrudescence, respectively.

Long‐day animals maintained reproductive functionality and displayed low aggression across all time points. By week 10, short‐day reproductively responsive females underwent gonadal regression and displayed increased aggression; non‐responsive animals showed no such changes. At week 24, animals were in a transitional period and displayed an intermediate phenotype with respect to reproduction and aggression. By week 30, short‐day females were fully recrudesced and returned to long‐day‐like levels of aggression.

Consistent with our hypothesis, gonadally regressed females displayed decreases in 17β‐oestradiol (oestradiol) levels, but site‐specific increases in the abundance of brain oestrogen receptor‐alpha (ERα) in regions associated with aggression, but not reproduction. Increased site‐specific ERα may function as a compensatory mechanism to allow increased responsiveness to oestradiol in regulating aggression in lieu of high circulating concentrations of hormones.

Collectively, these results broaden our understanding of how breeding phenology maps onto social behaviour and the mechanisms that have evolved to coordinate behaviours that occur in non‐breeding contexts.

A lay summary is available for this article.
Extended dispersal kernels in a changing world: insights from statistics of extremes
Authors: García Cristina , Borda‐de‐Água Luís
Published: December 2016

Dispersal ecology is a topical discipline that involves understanding and predicting plant community responses to multiple drivers of global change. Propagule movements that entail long‐distance dispersal (LDD) events are crucial for plants to reach and colonize suitable sites across fragmented landscapes. Yet, LDD events are extremely rare, and thus, obtaining reliable estimates of the maximum distances that propagules move across and of their frequency has been a long‐lasting challenge in plant ecology. Recent advances in dispersal ecology have provided reliable records of dispersal distances, but they remain confined to focal populations, limiting our ability to infer the frequency and actual extent of LDD events across landscapes.

In this study, we view LDD events as extreme values of a dispersal function, and we apply statistics of extremes to derive the frequency and extent of LDD events of simulated and empirical data sets. We first briefly explain the rationale behind statistics of extremes, and we then illustrate how dispersal ecology can benefit conceptually and analytically from applying extreme value analyses. We apply the block maxima approach to simulated seed shadows, and we apply the peak over a threshold method to empirical data sets that contain pollen and seed dispersal distances recorded for a population of Prunus mahaleb, an insect‐pollinated and vertebrate‐dispersed tree species.

Diagnostic plots reveal a distance threshold of υ = 80 m for pollen grains and of υ = 170 m for dispersed seeds. Values that exceed the threshold fit a light‐tailed distribution function for pollen and fit a fat‐tailed Pareto distribution for seed dispersal distances. Both distribution functions estimate a low (but nonzero) conditional probability of reaching distant locations, extending well beyond the borders of our focal population as follows: Pr (X ≥ 1 km) = 9 × 10−5 for pollen grains and Pr (X ≥ 10 km) = 7 × 10−5 for dispersed seeds.

Synthesis. Dispersal ecologists can take the most of their dispersal distance records by applying statistics of extremes to infer the probability of occurrence of extremely rare, but crucial, long distance dispersal events that reach locations well beyond focal populations.
What is long‐distance dispersal? And a taxonomy of dispersal events
Authors: Jordano Pedro
Published: December 2016

Dispersal is a key individual‐based process influencing many life‐history attributes and scaling up to population‐level properties (e.g. metapopulation connectivity). A persistent challenge in dispersal ecology has been the robust characterization of dispersal functions (kernels), a fundamental tool to predict how dispersal processes respond under global change scenarios. Particularly, the rightmost tail of these functions, that is the long‐distance dispersal (LDD) events, are difficult to characterize empirically and to model in realistic ways.

But, when is it a LDD event? In the specific case of plants, dispersal has three basic components: (i) a distinct (sessile) source, the maternal plant producing the fruits or the paternal tree acting as a source of pollen; (ii) a distance component between source and target locations; and (iii) a vector actually performing the movement entailing the dispersal event. Here, I discuss operative definitions of LDD based on their intrinsic properties: (i) events crossing geographic boundaries among stands; and (ii) events contributing to effective gene flow and propagule migration.

Strict‐sense long‐distance dispersal involves movement both outside the stand geographic limits and outside the genetic neighbourhood area of individuals. Combinations of propagule movements within/outside these two spatial reference frames result in four distinct modes of LDD.

Synthesis. I expect truncation of seed dispersal kernels to have multiple consequences on demography and genetics, following to the loss of key dispersal services in natural populations. Irrespective of neighbourhood sizes, loss of LDD events may result in more structured and less cohesive genetic pools, with increased isolation by distance extending over broader areas. Proper characterization of the LDD events helps to assess, for example, how the ongoing defaunation of large‐bodied frugivores pervasively entails the loss of crucial LDD functions.
Dispersal processes driving plant movement: challenges for understanding and predicting range shifts in a changing world
Authors: García Cristina , Klein Etienne K. , Jordano Pedro
Published: December 2016

Dispersal ecology is a broad topical discipline that tackles important conceptual and applied issues, such as the study of the ability of plants to transmit their propagules across fragmented and managed landscapes.

The relevance of dispersal for plant populations is threefold because: (i) dispersal processes scale from genes and individuals that disperse (or produce propagules to be dispersed) to population dynamics and both local and regional distribution patterns; (ii) by dispersing propagules or individuals and the genes they carry, dispersal inherently links demographic and genetic dynamics across the landscape; and (iii) dispersal elicits key ecological and evolutionary processes that sustain biodiversity, such as species assembly in species‐rich communities. The steady improvement of tracking devices and molecular tools that trace the movement or infer provenance of organisms and the pressing need to address conservation issues have expanded the disciplinary boundaries of dispersal ecology.

The discussion on the main advances on and challenges for dispersal ecology was the main motivation for the organization of a thematic topic session entitled Dispersal processes driving plant movement: challenges for understanding and predicting range shifts in a changing world at the Annual Meeting of the British Ecological Society (2015, Edinburgh). This session brought together researchers with different types of expertise and interests on dispersal processes and their contributions are now included in this special feature together with a few additional articles.

Synthesis. Overall, this special feature illustrates that dispersal ecology spans a broad range of research topics by integrating eight contributions that cover key aspects of this discipline: from conceptual and methodological advances to the study of the ecological and evolutionary outcomes.