bluuebunny/crossref_metadata_2025 huggingface dataset:
Low Back Pain: Investigation of Biases in Outpatient Canadian Physical Therapy
Authors: Laliberté Maude , Mazer Barbara , Orozco Tatiana , Chilingaryan Gevorg , Williams-Jones Bryn , Hunt Matthew , Feldman Debbie Ehrmann
Published: May 2017

Background

Previous research suggested that physical therapy services can be influenced by patient characteristics (age, sex, socioeconomic status) or insurance status rather than their clinical need.

Objective

The aim of this study was to determine whether patient-related factors (age, sex, SES) and the source of reimbursement for physical therapy services (insurance status) influence wait time for, frequency of, and duration of physical therapy for low back pain.

Design

This study was an empirical cross-sectional online survey of Canadian physical therapy professionals (defined as including physical therapists and physical rehabilitation specialists).

Methods

A total of 846 physical therapy professionals received 1 of 24 different (and randomly selected) clinical vignettes (ie, patient case scenarios) and completed a 40-item questionnaire about how they would treat the fictional patient in the vignette as well as their professional clinical practice. Each vignette described a patient with low back pain but with variations in patient characteristics (age, sex, socioeconomic status) and insurance status (no insurance, private insurance, Workers’ Compensation Board insurance).

Results

The age, sex, and socioeconomic status of the fictional vignette patients did not affect how participants would provide service. However, vignette patients with Workers’ Compensation Board insurance would be seen more frequently than those with private insurance or no insurance. When asked explicitly, study participants stated that insurance status, age, and chronicity of the condition were not factors associated with wait time for, frequency of, or duration of treatment.

Limitations

This study used a standardized vignette patient and may not accurately represent physical therapy professionals’ actual clinical practice.

Conclusions

There appears to be an implicit professional bias in relation to patients’ insurance status; the resulting inequity in service provision highlights the need for further research as a basis for national guidelines to promote equity in access to and provision of quality physical therapy services.
A Workflow for Extracting Plot-level Biophysical Indicators From Aerially Acquired Multispectral Imagery
Authors: Wallhead Matthew , Zhu Heping , Sulik John , Stump William
Published: May 2017

Advances in technologies associated with unmanned aerial vehicles (UAVs) have allowed researchers, farmers and agribusinesses to incorporate UAVs coupled with imaging systems into data collection and decision making. Multispectral imagery allows for a quantitative assessment of biophysical indicators or plant health status. What is needed now is a standardized workflow for the quantitative assessment of plant biophysical indicators using low-altitude, high-resolution, UAV-acquired multispectral imagery. With this need in mind, the authors developed and proposed a workflow for extracting plot-level vegetation index means from orthomosaics. As the use of UAVs and associated data collection activities expands, it will become increasingly important that data is being properly incorporated and utilized by ag professionals.
The Crucible simulation: Behavioral simulation improves clinical leadership skills and understanding of complex health policy change
Authors: Cohen Daniel , Vlaev Ivo , McMahon Laurie , Harvey Sarah , Mitchell Andy , Borovoi Leah , Darzi Ara
Published: May 2017

Background:

The Health and Social Care Act 2012 represents the most complex National Health Service reforms in history. High-quality clinical leadership is important for successful implementation of health service reform. However, little is known about the effectiveness of current leadership training.

Purpose:

This study describes the use of a behavioral simulation to improve the knowledge and leadership of a cohort of medical doctors expected to take leadership roles in the National Health Service.

Methodology:

A day-long behavioral simulation (The Crucible) was developed and run based on a fictitious but realistic health economy. Participants completed pre- and postsimulation questionnaires generating qualitative and quantitative data. Leadership skills, knowledge, and behavior change processes described by the “theory of planned behavior” were self-assessed pre- and postsimulation.

Results:

Sixty-nine medical doctors attended. Participants deemed the simulation immersive and relevant. Significant improvements were shown in perceived knowledge, capability, attitudes, subjective norms, intentions, and leadership competency following the program. Nearly one third of participants reported that they had implemented knowledge and skills from the simulation into practice within 4 weeks.

Conclusions:

This study systematically demonstrates the effectiveness of behavioral simulation for clinical management training and understanding of health policy reform. Potential future uses and strategies for analysis are discussed.

Practice Implications:

High-quality care requires understanding of health systems and strong leadership. Policymakers should consider the use of behavioral simulation to improve understanding of health service reform and development of leadership skills in clinicians, who readily adopt skills from simulation into everyday practice.
Reaction of the BCG Scar in the Acute Phase of Kawasaki Disease in Mexican Children
Authors: Garrido-García Luis Martín , Castillo-Moguel Ariel , Vázquez-Rivera Mirella , Cravioto Patricia , Fernando Galván
Published: May 2017

Background:

Kawasaki disease (KD) is an acute self-limited systemic vasculitis that primarily affects children <5 years old. There is no specific diagnostic test. A reaction at the Bacille Calmette-Guérin (BCG) inoculation site has been reported as a common finding in patients with KD where BCG vaccination is mandatory. The purpose of this study was to evaluate the frequency of reactivation of the BCG in Mexican children diagnosed with KD.

Methods:

A retrospective study of all patients diagnosed with KD from August 1, 1995, to August 31, 2015, at our Institution was performed. The clinical profile, laboratory results, treatment used and coronary artery abnormalities in the BCG reactive and the BCG nonreactive groups were analyzed and compared.

Results:

We included 399 patients with KD. Ninety-seven (24.3%) had BCG reaction at the inoculation site. The BCG(+) group was younger than the BCG(−) group (P< 0.000). There were 18 (18.55%) incomplete cases in the BCG(+) group compared with 65 (21.52%) in the BCG(−) group without statistical significance. The BCG+ group developed coronary artery aneurysms in 37 cases and the BCG(−) group developed coronary artery aneurysms in 111 cases without statistical significance. Multivariate analysis showed that younger age at diagnosis was the only variable associated with a reaction at the BCG inoculation site in patients with KD.

Conclusions:

In Mexico, a country with a National BCG Vaccination Program and a low incidence of KD, reaction at the BCG inoculation site could be a useful diagnostic sign of KD.
Borrelia miyamotoi Polymerase Chain Reaction Positivity on a Tick-Borne Disease Panel in an Endemic Region of Rhode Island
Authors: Fiorito Theresa M. , Reece Rebecca , Flanigan Timothy P. , Silverblatt Fredric J.
Published: May 2017

Background

Borrelia miyamotoi is a newer cause of ixodid (hard-bodied) tick-borne illness. Because symptoms are generally nonspecific and pathognomonic clinical features are lacking, whole blood polymerase chain reaction (PCR) may be useful for confirming a diagnosis. A tick-borne disease panel (“TBD-3”) bundled with Borrelia species (including B. miyamotoi) PCR (“TBD-3M”) was offered for patients with suspicion of TBD during 2014–2015 at South County Hospital in Rhode Island, an endemic region for many tick-borne illnesses.

Materials and Methods

Imugen laboratory was queried for all TBD-3M panels and Borrelia PCR’s sent from South County Hospital patients between January 1, 2014, and August 31, 2015. One positive whole blood B. miyamotoi PCR sample (genus and species specific) was considered evidence for B. miyamotoi infection. Demographics, clinical presentations, coinfections, laboratory abnormalities, and treatment courses for B. miyamotoi disease were examined.

Results

A total of 2324 patients had a bundled tick-borne panel performed for unexplained fever and other symptoms. In addition, 258 patients had individual Borrelia PCR’s performed. Overall, 78 patients were positive for B. burgdorferi PCR (3.0% positivity rate) and 18 patients were positive for B. miyamotoi PCR (0.7% positivity rate). Most patients presented with a “summer influenza”–like illness (94% reporting fever). Sixteen of these 18 patients were empirically prescribed doxycycline. One patient was concomitantly positive for B. miyamotoi PCR, B. microti PCR, and IgM Lyme antibodies. Three additional B. miyamotoi positive patients had positive Lyme serology.

Conclusions

Borrelia whole blood PCR was bundled to a pre-existing tick-borne panel to potentially account for unexplained fevers and other nonlocalizing symptoms in high-risk patients. Treatment recommendations for B. miyamotoi are based on case reports of successful treatments in other causes of relapsing fever, and the same antibiotics regimens are used for both. The utility of B. miyamotoi PCR in first-line screening of patients with unexplained fever may be minimal, given the low positivity rate observed and uniform effective empiric treatments prescribed.
Real-Time Intracochlear Electrocochleography Obtained Directly Through a Cochlear Implant
Authors: Harris Michael S. , Riggs William Jason , Koka Kanthaiah , Litvak Leonid M. , Malhotra Prashant , Moberly Aaron C. , O’Connell Brendan P. , Holder Jourdan , Di Lella Federico Alberto , Boccio Carlos Mario , Wanna George B. , Labadie Robert F. , Adunka Oliver F.
Published: May 2017

Hypothesis:

Utilizing the cochlear implant to record electrophysiologic responses during device placement is a feasible and efficacious technique for monitoring near real-time cochlear physiology during and following electrode insertion.

Background:

Minimizing intracochlear trauma during cochlear implantation has emerged as a highly researched area to help improve patient performance. Currently, conventional cochlear implant technology allows for the recording of electrically evoked compound action potentials (eCAPs). Acoustically evoked potentials may be more sensitive in detecting physiologic changes occurring as a result of electrode insertion. Electrocochleography obtained from within the cochlea allows hair cell and neural response monitoring along the cochlear spiral at locations where changes most likely would occur.

Methods:

Intracochlear electrocochleography (ECochG) was recorded from the cochlear implant during surgery in 14 subjects. A long acquisition time (54.5 ms), capable of measuring potentials from the low frequency-serving apical region of the cochlea (125 and 500 Hz) was employed. Two distinct intracochlear processing methods were used and compared in obtaining electrophysiologic data.

Results:

Measureable intracochlear ECochG responses were obtained from all 14 participants. The 1st harmonic distortions (cochlear microphonic and auditory nerve neurophonic) generally increased steadily with electrode insertion. Electrode and frequency scan following insertion revealed that response amplitude varied based on location of recording electrode and frequency of stimulation. Exquisite sensitivity to manipulation during round window muscle packing was demonstrated.

Conclusion:

Intracochlear ECochG recorded from the electrode array of the cochlear implant is a highly feasible technique that sheds light on cochlear micromechanics during cochlear implant electrode placement.
The Potential Return on Public Investment in Detecting Adverse Drug Effects
Authors: Huybrechts Krista F. , Desai Rishi J. , Park Moa , Gagne Joshua J. , Najafzadeh Mehdi , Avorn Jerry
Published: May 2017

Background:

Many countries lack fully functional pharmacovigilance programs, and public budgets allocated to pharmacovigilance in industrialized countries remain low due to resource constraints and competing priorities.

Objective:

Using 3 case examples, we sought to estimate the public health and economic benefits resulting from public investment in active pharmacovigilance programs to detect adverse drug effects.

Research Design:

We assessed 3 examples in which early signals of safety hazards were not adequately recognized, resulting in continued exposure of a large number of patients to these drugs when safer and effective alternative treatments were available. The drug examples studied were rofecoxib, cerivastatin, and troglitazone. Using an individual patient simulation model and the health care system perspective, we estimated the potential costs that could have been averted by early systematic detection of safety hazards through the implementation of active surveillance programs.

Results:

We found that earlier drug withdrawal made possible by active safety surveillance would most likely have resulted in savings in direct medical costs of $773–$884 million for rofecoxib, $3–$10 million for cerivastatin, and $38–$63 million for troglitazone in the United States through the prevention of adverse events. By contrast, the yearly public investment in Food and Drug Administration initiated population-based pharmacovigilance activities in the United States is about $42.5 million at present.

Conclusion:

These examples illustrate a critical and economically justifiable role for active adverse effect surveillance in protecting the health of the public.
Perceived Impairment in Sports Participation in Adolescents With Inflammatory Bowel Diseases
Authors: Plevinsky Jill M. , Wojtowicz Andrea A. , Poulopoulos Natasha , Schneider Kristin L. , Greenley Rachel N.
Published: May 2017

Objective:

Physical activity (PA) is important for adolescents with inflammatory bowel diseases (IBDs) given the increased risk of developing osteoporosis and the increased risk of IBD‐related complications among those with IBD and obesity. Symptoms such as fatigue, abdominal pain, nausea, and frequent bowel movements can interfere with PA. Sports participation is an important source of PA for adolescents; however, the extent to which IBD interferes with sports participation is unstudied. The present study aimed to examine demographic, health‐related, physical, and psychosocial correlates of perceived impairment in sports participation.

Method:

Seventy‐six adolescents (M[SD] = 14.5 [1.8] years, 45% girls) completed surveys of perceived impairment in sports participation, demographics, physical health, and psychosocial health. Physicians rated disease activity at enrolment. All participants were diagnosed with IBD for at least a year and prescribed a daily oral medication.

Results:

Nearly half of participants reported at least occasional interference in sports participation because of their IBD. Active disease (P = 0.014), older age (P = 0.006), and poorer disease‐specific quality of life, and quality of life in physical health and psychosocial domains were associated with greater impairment in sports participation in bivariate analyses (P < 0.001). In regression analyses, systemic disease‐related symptoms, body image concerns, and older age emerged as the strongest predictors of impairment in sports participation (P < 0.05).

Conclusions:

Older adolescents, those with greater systemic symptoms, and those with poorer body image may be particularly at risk for impairment in sports participation. Addressing barriers to sports participation may be a useful strategy in enhancing PA in this patient group.
Molecular Profiling Reveals a Clonal Relationship Between Ovarian Mucinous Tumors and Corresponding Mural Carcinomatous Nodules
Authors: Mesbah Ardakani Nima , Giardina Tindaro , Amanuel Benhur , Stewart Colin J.
Published: May 2017

Benign or malignant mural nodules rarely occur in mucinous tumors (MTs) of the ovary and malignant nodules can show mesenchymal or epithelial differentiation. The histogenesis of mural nodules is unclear and it has been suggested that these may evolve through divergent differentiation of the mucinous neoplasm or alternatively represent a collision phenomenon. To test these possibilities we compared the molecular profile of 7 ovarian MTs with their matched mural carcinomatous nodules (MCNs) by next-generation sequencing. We found identical KRAS mutations in paired MTs and MCNs in 6 cases, one of which also showed identical CDH1 mutations in both components. In 1 tumor a KRAS mutation was detected in the mucinous neoplasm but not in the MCN; however, identical p53 mutations were present in both tumor elements. Unpaired p53 and PTEN mutations were detected only in the MCN in 2 cases, while mutations in p53 and PIK3CA genes were observed only in the MT in 2 cases. The overall comparative genomic profile was consistent with the neoplastic nature of the MCNs and strongly supported their clonal relationship with the more differentiated mucinous neoplasms. MCNs possibly develop through the acquisition of additional genomic alterations, such as p53 and PTEN mutations, resulting in an anaplastic morphologic phenotype. Our findings also suggest that ovarian MTs with MCNs often arise in KRAS mutant neoplasms. However, mutations in other genes such as PIK3CA and CDH1 may play a role in the neoplastic evolution of a subset of these tumors.
Fornix Structural Connectivity and Allostatic Load: Empirical Evidence From Schizophrenia Patients and Healthy Controls
Authors: Savransky Anya , Chiappelli Joshua , Rowland Laura M. , Wisner Krista , Shukla Dinesh K. , Kochunov Peter , Hong L. Elliot
Published: May 2017

Objective

The fornix is a white matter tract carrying the fibers connecting the hippocampus and the hypothalamus, two essential stress-regulatory structures of the brain. We tested the hypothesis that allostatic load (AL), derived from a battery of peripheral biomarkers indexing the cumulative effects of stress, is associated with abnormalities in brain white matter microstructure, especially the fornix, and that higher AL may help explain the white matter abnormalities in schizophrenia.

Methods

Using 13 predefined biomarkers, we tested AL in 44 schizophrenic patients and 33 healthy controls. Diffusion tensor imaging was used to obtain fractional anisotropy (FA) values of the fornix and other white matter tracts.

Results

AL scores were significantly elevated in patients compared with controls (F(3,77) = 7.87,p= .006). AL was significantly and inversely correlated with FA of fornix in both controls (r= −.58,p= .001) and patients (r= −.36,p= .023). Several nominally significant (p< .05 but did not survive Bonferroni correction for multiple comparison) correlations were also observed between AL and FA of other white matter tracts in schizophrenic patients. However, the fornix was the only tract exhibiting a correlation with AL in both groups.

Conclusions

These results provide initial evidence that allostatic processes are linked to fornix microstructure in clinical participants.
Effectiveness of a Stepped, Collaborative, and Coordinated Health Care Network for Somatoform Disorders (Sofu-Net): A Controlled Cluster Cohort Study
Authors: Löwe Bernd , Piontek Katharina , Daubmann Anne , Härter Martin , Wegscheider Karl , König Hans-Helmut , Shedden-Mora Meike
Published: May 2017

Objective

Stepped, collaborative, and coordinated approaches have been proposed as the optimal treatment strategy for somatic symptom and related disorders, but evidence supporting this strategy is lacking. The aim of this study was to assess the effectiveness of a guideline-based health care network for patients who are at high risk of somatoform disorder (Sofu-Net).

Methods

In a controlled, prospective, observer-blinded cluster cohort study, patients who were at high risk of somatoform disorder were recruited at 18 primary care practices in the Sofu-Net and at 15 primary care practices that provided care as usual (CAU). The primary outcome at 6-month follow-up was the rate at which the patients received mental health treatment since the establishment of Sofu-Net. The secondary outcomes included the patients' clinical symptom severity.

Results

A total of 119 patients in the Sofu-Net intervention group and 100 patients in the CAU control group who were at high risk of somatoform disorder were followed for 6 months. A significantly greater proportion of Sofu-Net patients than CAU patients received mental health treatment (47.9% versus 31.0%; odds ratio = 1.96; 95% confidence interval, 1.07–3.58). However, the Sofu-Net group did not show greater reductions in clinical symptom burden compared with the CAU group.

Conclusions

The treatment of somatoform disorders within a guideline-based health care network resulted in increased rates of mental health treatment but failed to improve patient clinical outcomes. Future investigations are needed to investigate the combined value of health care networks with specialized psychotherapy interventions in patients at high risk of somatic symptom and related disorders.

Trial Registration: ISRCTN55870770.
Impact of Mother–Infant Pair Clinics and Short-Text Messaging Service (SMS) Reminders on Retention of HIV-Infected Women and HIV-Exposed Infants in eMTCT Care in Malawi: A Cluster Randomized Trial
Authors: Mwapasa Victor , Joseph Jessica , Tchereni Timothy , Jousset Aurelie , Gunda Andrews
Published: May 2017

Background:

Poor retention of mothers and HIV-exposed infants (HEIs) in HIV care threatens efforts to eliminate pediatric HIV. Novel strategies are required to address this challenge. We compared 12-month maternal and HEI postpartum retention in health facilities implementing the following HIV care delivery models: integrated HIV and maternal, neonatal, and child health services [mother–infant pair (MIP) clinics], MIP clinics plus short-text messaging service (SMS) reminders to prevent default (MIP + SMS), and standard of care (SOC).

Methods:

From May 2013 to August 2016, a cluster randomized trial was conducted in rural Malawi, which randomized 30 health facilities to the 3 service delivery models. HIV+ pregnant women and HEIs were enrolled and followed up to monitor compliance with prescheduled visits and retention. Log binomial regression, using generalized estimated equation, was used to assess the impact of the models on retention.

Results:

The trial enrolled 461, 493, and 396 HIV+ pregnant women and 386, 399, and 300 HEIs into the MIP, MIP + SMS, and SOC arms, respectively. Compared with the 12-month maternal retention rate in the SOC arm (22.2%), the rates were similar in the MIP arm [19.3%, risk ratio (RR): 0.85, 95% confidence interval (CI): 0.56 to 1.30] and in the MIP + SMS arm (24.9%, RR: 1.08, 95% CI: 0.87 to 1.35). Compared with the 12-month infant retention rate in the SOC arm (9.8%), the rates were similar in the MIP arm (8.0%, RR: 0.89, 95% CI: 0.31 to 2.58) and in the MIP + SMS arm (19.5%, RR: 1.40, 95% CI: 0.85 to 2.31).

Conclusions:

MIP and MIP + SMS service delivery models were ineffective in improving maternal and infant retention in rural Malawi.
The Impact of Structured Mentor Mother Programs on Presentation for Early Infant Diagnosis Testing in Rural North-Central Nigeria: A Prospective Paired Cohort Study
Authors: Sam-Agudu Nadia A. , Ramadhani Habib O. , Isah Christopher , Erekaha Salome , Fan-Osuala Chinenye , Anaba Udochisom , Adejuyigbe Ebunoluwa A. , Charurat Manhattan
Published: May 2017

Background:

Early infant diagnosis (EID) by 2 months of age is an important prevention of mother-to-child cascade step that serves as an early postpartum indicator of program success. Uptake and timely presentation for infant HIV diagnosis are significant challenges in resource-limited settings. Few studies on maternal peer support (PS) have demonstrated impact on EID. The MoMent study evaluated the impact of structured PS on timely presentation for EID testing in rural North-Central Nigeria.

Methods:

A total of 497 HIV-positive pregnant women were consecutively recruited at 10 primary health care centers with structured, closely supervised Mentor Mother (MM) support, and 10 pair-matched primary health care centers with routine but ad hoc PS. EID was assessed among HIV-exposed infants delivered to recruited women, and was defined by presentation for DNA polymerase chain reaction testing between 35 and 62 days of life. A logistic regression model with generalized estimating equation to account for clustering was used to assess the effect of MMs on EID presentation.

Results:

Data from 408 live-born infants were available for analysis. Exposure to MM support was associated with higher odds of timely EID presentation among infants, compared with routine PS (adjusted odds ratios = 3.7, 95% confidence interval: 2.8 to 5.0).

Conclusions:

Closely supervised, organized MM support significantly improved presentation for EID among HIV-exposed infants in a rural Nigerian setting. Structured PS can improve rates of timely EID presentation and potentially the uptake of EID testing in resource-limited settings.
The Impact of Structured Mentor Mother Programs on 6-Month Postpartum Retention and Viral Suppression among HIV-Positive Women in Rural Nigeria: A Prospective Paired Cohort Study
Authors: Sam-Agudu Nadia A. , Ramadhani Habib O. , Isah Christopher , Anaba Udochisom , Erekaha Salome , Fan-Osuala Chinenye , Galadanci Hadiza , Charurat Manhattan
Published: May 2017

Background:

Peer support (PS) has reportedly improved Prevention of mother-to-child transmission (PMTCT) outcomes in high HIV-burden settings; however, evidence of impact on retention in care is limited. Retention in care implies consistent engagement and treatment adherence. The MoMent study evaluated the impact of structured vs unstructured PS on postpartum retention and viral load suppression among rural Nigerian women.

Methods:

A total of 497 HIV-positive pregnant women were consecutively enrolled at 10 primary health care centers with structured mentor mother (MM) support, and at 10 pair-matched primary health care centers with routine, ad hoc PS. The structured MM intervention comprised an outcome-specific scope of work, close MM supervision, standardized documentation, performance evaluations, and retraining as appropriate. Retention was defined by clinic attendance during the first 6-month postpartum. Participants with ≥3 of 6 expected monthly visits were considered retained. Women with a 6-month postpartum plasma viral load of <20 copies/mL were considered suppressed. A logistic regression model with generalized estimating equation was used to assess the effect of MMs on retention and viral suppression.

Results:

Exposure to structured MM support was associated with higher odds of retention than routine PS (adjusted odds ratio = 5.9, 95% confidence interval: 3.0 to 11.6). Similarly, the odds of viral suppression at 6-month postpartum were higher for MM-supported women (adjusted odds ratio = 4.9, 95% confidence interval: 2.6 to 9.2).

Conclusions:

Structured PS significantly improved postpartum PMTCT retention and viral suppression rates among women in rural Nigeria. Introduction of structure can enhance the impact of PS interventions on PMTCT outcomes.
Impact of Facility- and Community-Based Peer Support Models on Maternal Uptake and Retention in Malawi's Option B+ HIV Prevention of Mother-to-Child Transmission Program: A 3-Arm Cluster Randomized Controlled Trial (PURE Malawi)
Authors: Phiri Sam , Tweya Hannock , van Lettow Monique , Rosenberg Nora E. , Trapence Clement , Kapito-Tembo Atupele , Kaunda-Khangamwa Blessings , Kasende Florence , Kayoyo Virginia , Cataldo Fabian , Stanley Christopher , Gugsa Salem , Sampathkumar Veena , Schouten Erik , Chiwaula Levison , Eliya Michael , Chimbwandira Frank , Hosseinipour Mina C. ,   the PURE Malawi Consortium
Published: May 2017

Background:

Many sub-Saharan African countries have adopted Option B+, a prevention of mother-to-child transmission approach providing HIV-infected pregnant and lactating women with immediate lifelong antiretroviral therapy. High maternal attrition has been observed in Option B+. Peer-based support may improve retention.

Methods:

A 3-arm stratified cluster randomized controlled trial was conducted in Malawi to assess whether facility- and community-based peer support would improve Option B+ uptake and retention compared with standard of care (SOC). In SOC, no enhancements were made (control). In facility-based and community-based models, peers provided patient education, support groups, and patient tracing. Uptake was defined as attending a second scheduled follow-up visit. Retention was defined as being alive and in-care at 2 years without defaulting. Attrition was defined as death, default, or stopping antiretroviral therapy. Generalized estimating equations were used to estimate risk differences (RDs) in uptake. Cox proportional hazards regression with shared frailties was used to estimate hazard of attrition.

Results:

Twenty-one facilities were randomized and enrolled 1269 women: 447, 428, and 394 in facilities that implemented SOC, facility-based, and community-based peer support models, respectively. Mean age was 27 years. Uptake was higher in facility-based (86%; RD: 6%, confidence interval [CI]: −3% to 15%) and community-based (90%; RD: 9%, CI: 1% to 18%) models compared with SOC (81%). At 24 months, retention was higher in facility-based (80%; RD: 13%, CI: 1% to 26%) and community-based (83%; RD: 16%, CI: 3% to 30%) models compared with SOC (66%).

Conclusions:

Facility- and community-based peer support interventions can benefit maternal uptake and retention in Option B+.
Impact of Facility-Based Mother Support Groups on Retention in Care and PMTCT Outcomes in Rural Zimbabwe: The EPAZ Cluster-Randomized Controlled Trial
Authors: Foster Geoff , Orne-Gliemann Joanna , Font Hélène , Kangwende Abigail , Magezi Vhumani , Sengai Tonderai , Rusakaniko Simba , Shumba Bridget , Zambezi Pemberai , Maphosa Talent
Published: May 2017

Background:

Prevention of mother-to-child transmission elimination goals are hampered by low rates of retention in care. The Eliminating Paediatric AIDS in Zimbabwe project assessed whether mother support groups (MSGs) improve rates of retention in care of HIV-exposed infants and their HIV-positive mothers, and maternal and infant outcomes.

Methods:

The study involved 27 rural clinics in eastern Zimbabwe. MSGs were established in 14 randomly selected clinics and met every 2 weeks coordinated by volunteer HIV-positive mothers. MSG coordinators provided health education and reminded mothers of MSG meetings by cell phone. Infant retention in care was defined as “12 months postpartum point attendance” at health care visits of HIV-exposed infants at 12 months of age. We also measured regularity of attendance and other program indicators of HIV-positive mothers and their HIV-exposed infants.

Results:

Among 507 HIV-positive pregnant women assessed as eligible, 348 were enrolled and analyzed (69%) with mothers who had disclosed their HIV status being overrepresented. In the intervention arm, 69% of infants were retained in care at 12 months versus 61% in the control arm, with no statistically significant difference. Retention and other program outcomes were systematically higher in the intervention versus control arm, suggesting trends toward positive health outcomes with exposure to MSGs.

Discussion:

We were unable to show that facility-based MSGs improved retention in care at 12 months among HIV-exposed infants. Selective enrollment of mothers more likely to be retained-in-care may have contributed to lack of effect. Methods to increase the impact of MSGs on retention including targeting of high-risk mothers are discussed.
Volatile Decay Products in Breath During Peritonitis Shock are Attenuated by Enteral Blockade of Pancreatic Digestive Proteases
Authors: DeLano Frank A. , Chow Jason , Schmid-Schönbein Geert W.
Published: May 2017

There is a need to develop markers for early detection of organ failure in shock that can be noninvasively measured at point of care. We explore here the use of volatile organic compounds (VOCs) in expired air in a rat peritonitis shock model. Expired breath samples were collected into Tedlar gas bags and analyzed by standardized gas chromatography. The gas chromatograms were digitally analyzed for presence of peak amounts over a range of Kovach indices. Following the induction of peritonitis, selected volatile compounds were detected within about 1 h, which remained at elevated amounts over a 6 h observation period. These VOCs were not present in control animals without peritonitis. Comparisons with know VOCs indicate that they include 1,4-diaminobutane and trimethylamine N-oxide. When pancreatic digestive proteases were blocked with tranexamic acid in the intestine and peritoneum, a procedure that serves to reduce organ failure in shock, the amounts of VOCs in the breath decreased spontaneously to control values without peritonitis. These results indicate that peritonitis shock is accompanied by development of volatile organic compounds that may be generated by digestive enzymes in the small intestine. VOCs may serve as indicators for detection of early forms of autodigestion by digestive proteases.
Topical Application of Mesenchymal Stromal Cells Ameliorated Liver Parenchyma Damage After Ischemia-Reperfusion Injury in an Animal Model
Authors: Lam Ping Kuen , Chong Charing Ching Ning , Lo Anthony Wing Ip , Chan Anthony Wing Hung , Tong Cindy See Wai , Chin Don Wai Ching , Wong Kenneth Hoi Kin , Choy Richard Kwong Wai , Fung Andrew Kai-Yip , Wang Yi Xiang , To Ka Fai , Lai Paul Bo San
Published: May 2017

Background

Ischemia-reperfusion injury (IRI) is commonly encountered after liver surgery. This study evaluated the hepatoprotective effects of topically applied adipose-derived mesenchymal stromal cells (ADMSCs) on hepatic IRI in a rat model.

Methods

ADMSCs from transgenic green fluorescent protein Sprague-Dawley rats were topically applied to the liver surface of Sprague-Dawley rats after hepatic IRI and fixed in position by fibrin glue (group A, n = 24). An equivalent amount of ADMSCs were administered through the portal (group B, n = 24) or tail vein (group C, n = 24). In the control group (group D, n = 20), no treatment was given to the IRI liver.

Results

All the rats in group A and group D survived. Within 2 days after hepatic IRI, only 50% of rats survived in group B, and ADMSCs were detected in thromboemboli within large vessels. 62.5% of the rats died in group C because most of the ADMSCs were trapped in the lungs. ADMSCs migrated across the liver capsule and homed to the injured liver parenchyma 3 days after topical application in group A. The homed ADMSCs expressed hepatocyte nuclear factor-4α and hepatocyte nuclear factor-1. Compared with group D, the rate of hepatic regeneration in group A was enhanced with less inflammation, smaller necrotic areas, and improved liver function. Proinflammatory cytokines IL-6, IL-21, and CD70 were significantly downregulated in group A by 6.3-, 2.7-, and 12.7-fold, respectively (P < 0.05). The neurogenic locus NOTCH homolog protein pathway was activated in the topical ADMSCs.

Conclusions

Topically applied adipose-derived mesenchymal stromal cells demonstrated hepatoprotective effects on hepatic IRI in an animal model.
Plant spines deter herbivory by restricting caterpillar movement
Authors: Kariyat Rupesh R. , Hardison Sean B. , De Moraes Consuelo M. , Mescher Mark C.
Published: May 2017

The spines of flowering plants are thought to function primarily in defence against mammalian herbivores; however, we previously reported that feeding by
Manduca sexta
caterpillars on the leaves of horsenettle plants (
Solanum carolinense
) induces increased development of internode spines on new growth. To determine whether and how spines impact caterpillar feeding, we conducted assays with three
Solanaceous
plant species that vary in spine numbers (
S. carolinense
,
S. atropurpureum
and
S. aethiopicum
) and also manipulated spine numbers within each species. We found that
M. sexta
caterpillars located experimentally isolated target leaves much more quickly on plants with experimentally removed spines compared with plants with intact spines. Moreover, it took caterpillars longer to defoliate species with relatively high spine numbers (
S. carolinense
and particularly
S
.
atropurpureum
) compared with
S. aethiopicum
, which has fewer spines
.
These findings suggest that spines may play a significant role in defence against insect herbivores by restricting herbivore movement and increasing the time taken to access feeding sites, with possible consequences including longer developmental periods and increased vulnerability or apparency to predators.
Targeting endogenous proteins for degradation through the affinity-directed protein missile system
Authors: Fulcher Luke J. , Hutchinson Luke D. , Macartney Thomas J. , Turnbull Craig , Sapkota Gopal P.
Published: May 2017

Targeted proteolysis of endogenous proteins is desirable as a research toolkit and in therapeutics. CRISPR/Cas9-mediated gene knockouts are irreversible and often not feasible for many genes. Similarly, RNA interference approaches necessitate prolonged treatments, can lead to incomplete knockdowns and are often associated with off-target effects. Targeted proteolysis can overcome these limitations. In this report, we describe an affinity-directed protein missile (AdPROM) system that harbours the von Hippel–Lindau (VHL) protein, the substrate receptor of the Cullin2 (CUL2) E3 ligase complex, tethered to polypeptide binders that selectively bind and recruit endogenous target proteins to the CUL2-E3 ligase complex for ubiquitination and proteasomal degradation. By using synthetic monobodies that selectively bind the protein tyrosine phosphatase SHP2 and a camelid-derived VHH nanobody that selectively binds the human ASC protein, we demonstrate highly efficient AdPROM-mediated degradation of endogenous SHP2 and ASC in human cell lines. We show that AdPROM-mediated loss of SHP2 in cells impacts SHP2 biology. This study demonstrates for the first time that small polypeptide binders that selectively recognize endogenous target proteins can be exploited for AdPROM-mediated destruction of the target proteins.
A new ankylosaurine dinosaur from the Judith River Formation of Montana, USA, based on an exceptional skeleton with soft tissue preservation
Authors: Arbour Victoria M. , Evans David C.
Published: May 2017

The terrestrial Judith River Formation of northern Montana was deposited over an approximately 4 Myr interval during the Campanian (Late Cretaceous). Despite having been prospected and collected continuously by palaeontologists for over a century, few relatively complete dinosaur skeletons have been recovered from this unit to date. Here we describe a new genus and species of ankylosaurine dinosaur,Zuul crurivastator, from the Coal Ridge Member of the Judith River Formation, based on an exceptionally complete and well-preserved skeleton (ROM 75860). This is the first ankylosaurin skeleton known with a complete skull and tail club, and it is the most complete ankylosaurid ever found in North America. The presence of abundant soft tissue preservation across the skeleton, includingin situosteoderms, skin impressions and dark films that probably represent preserved keratin, make this exceptional skeleton an important reference for understanding the evolution of dermal and epidermal structures in this clade. Phylogenetic analysis recoversZuulas an ankylosaurin ankylosaurid within a clade ofDyoplosaurusandScolosaurus, withEuoplocephalusbeing more distantly related within Ankylosaurini. The occurrence ofZ. crurivastatorfrom the upper Judith River Formation fills a gap in the ankylosaurine stratigraphic and geographical record in North America, and further highlights that Campanian ankylosaurines were undergoing rapid evolution and stratigraphic succession of taxa as observed for Laramidian ceratopsids, hadrosaurids, pachycephalosaurids and tyrannosaurids.
Dispersionless (3+1)-dimensional integrable hierarchies
Authors: Błaszak Maciej , Sergyeyev Artur
Published: May 2017

In this paper, we introduce a multi-dimensional version of the
R
-matrix approach to the construction of integrable hierarchies. Applying this method to the case of the Lie algebra of functions with respect to the contact bracket, we construct integrable hierarchies of (3+1)-dimensional dispersionless systems of the type recently introduced in Sergyeyev (2014 (
http://arxiv.org/abs/1401.2122
)).
Removal of an apex predator initiates a trophic cascade that extends from herbivores to vegetation and the soil nutrient pool
Authors: Morris Timothy , Letnic Mike
Published: May 2017

It is widely assumed that organisms at low trophic levels, particularly microbes and plants, are essential to basic services in ecosystems, such as nutrient cycling. In theory, apex predators' effects on ecosystems could extend to nutrient cycling and the soil nutrient pool by influencing the intensity and spatial organization of herbivory. Here, we take advantage of a long-term manipulation of dingo abundance across Australia's dingo-proof fence in the Strzelecki Desert to investigate the effects that removal of an apex predator has on herbivore abundance, vegetation and the soil nutrient pool. Results showed that kangaroos were more abundant where dingoes were rare, and effects of kangaroo exclusion on vegetation, and total carbon, total nitrogen and available phosphorus in the soil were marked where dingoes were rare, but negligible where dingoes were common. By showing that a trophic cascade resulting from an apex predator's lethal effects on herbivores extends to the soil nutrient pool, we demonstrate a hitherto unappreciated pathway via which predators can influence nutrient dynamics. A key implication of our study is the vast spatial scale across which apex predators' effects on herbivore populations operate and, in turn, effects on the soil nutrient pool and ecosystem productivity could become manifest.
Concerted and mosaic evolution of functional modules in songbird brains
Authors: Moore Jordan M. , DeVoogd Timothy J.
Published: May 2017

Vertebrate brains differ in overall size, composition and functional capacities, but the evolutionary processes linking these traits are unclear. Two leading models offer opposing views: the concerted model ascribes major dimensions of covariation in brain structures to developmental events, whereas the mosaic model relates divergent structures to functional capabilities. The models are often cast as incompatible, but they must be unified to explain how adaptive changes in brain structure arise from pre-existing architectures and developmental mechanisms. Here we show that variation in the sizes of discrete neural systems in songbirds, a species-rich group exhibiting diverse behavioural and ecological specializations, supports major elements of both models. In accordance with the concerted model, most variation in nucleus volumes is shared across functional domains and allometry is related to developmental sequence. Per the mosaic model, residual variation in nucleus volumes is correlated within functional systems and predicts specific behavioural capabilities. These comparisons indicate that oscine brains evolved primarily as a coordinated whole but also experienced significant, independent modifications to dedicated systems from specific selection pressures. Finally, patterns of covariation between species and brain areas hint at underlying developmental mechanisms.
Deep-Learning Based, Automated Segmentation of Macular Edema in Optical Coherence Tomography
Authors: Lee Cecilia S. , Tyring Ariel J. , Deruyter Nicolaas P. , Wu Yue , Rokem Ariel , Lee Aaron Y.
Published: May 2017

Evaluation of clinical images is essential for diagnosis in many specialties and the development of computer vision algorithms to analyze biomedical images will be important. In ophthalmology, optical coherence tomography (OCT) is critical for managing retinal conditions. We developed a convolutional neural network (CNN) that detects intraretinal fluid (IRF) on OCT in a manner indistinguishable from clinicians. Using 1,289 OCT images, the CNN segmented images with a 0.911 cross-validated Dice coefficient, compared with segmentations by experts. Additionally, the agreement between experts and between experts and CNN were similar. Our results reveal that CNN can be trained to perform automated segmentations.
Interpreting Temporal Fluctuations in Resting-State Functional Connectivity MRI
Authors: Liégeois Raphaël , Laumann Timothy O. , Snyder Abraham Z. , Zhou Juan , Yeo B.T. Thomas
Published: May 2017

Resting-state functional connectivity is a powerful tool for studying human functional brain networks. Temporal fluctuations in functional connectivity, i.e.,dynamicfunctional connectivity (dFC), are thought to reflect dynamic changes in brain organization andnon-stationaryswitching of discrete brain states. However, recent studies have suggested that dFC might be attributed to sampling variability of static FC. Despite this controversy, a detailed exposition of stationarity and statistical testing of dFC is lacking in the literature. This article seeks an in-depth exploration of these statistical issues at a level appealing to both neuroscientists and statisticians.

We first review the statistical notion of stationarity, emphasizing its reliance on ensemble statistics. In contrast, all FC measures depend on sample statistics. An important consequence is that the space of stationary signals is much broader than expected, e.g., encompassing hidden markov models (HMM) widely used to extract discrete brain states. In other words, stationarity does not imply the absence of brain states. We then expound the assumptions underlying the statistical testing of dFC. It turns out that the two popular frameworks - phase randomization (PR) and autoregressive randomization (ARR) - generate stationary, linear, Gaussian null data. Therefore, statistical rejection can be due to non-stationarity, nonlinearity and/or non-Gaussianity. For example, the null hypothesis can be rejected for the stationary HMM due to nonlinearity and non-Gaussianity. Finally, we show that a common form of ARR (bivariate ARR) is susceptible to false positives compared with PR and an adapted version of ARR (multivariate ARR).

Application of PR and multivariate ARR to Human Connectome Project data suggests that the stationary, linear, Gaussian null hypothesis cannot be rejected for most participants. However, failure to reject the null hypothesis does not imply that static FC can fully explain dFC. We find that first order AR models explain temporal FC fluctuations significantly better than static FC models. Since first order AR models encode both static FC and one-lag FC, this suggests the presence of dynamical information beyond static FC. Furthermore, even in subjects where the null hypothesis was rejected, AR models explain temporal FC fluctuations significantly better than a popular HMM, suggesting the lack of discrete states (as measured by resting-state fMRI). Overall, our results suggest that AR models are not only useful as a means for generating null data, but may be a powerful tool for exploring the dynamical properties of resting-state fMRI. Finally, we discuss how apparent contradictions in the growing dFC literature might be reconciled.