bluuebunny/crossref_metadata_2025 huggingface dataset:
Vertical sleeve gastrectomy improves indices of metabolic disease in rodent model of surgical menopause
Authors: Lawson William J. , Shirey Kristin , Spann Redin A. , Zamarripa Carlos A. , Hosler Jonathan P. , Grayson Bernadette E.
Published: November 2016

Objective:

Although women are the most common recipients of weight loss surgeries for the amelioration of the comorbidities of obesity, few studies have addressed the efficacy of these procedures with specific attention to reproductive stage. Here we ask in a rodent model of vertical sleeve gastrectomy (VSG) whether improvements to metabolic health are realized in women having received surgical menopause. Specifically we were interested in knowing whether rats made menopausal through surgical means would exhibit persistent hepatic steatosis as reported in previously pregnant, freely cycling female VSG rats or if it is resolved as reported in male VSG rats.

Methods:

All the rats first received ovariectomy (OVX) and then were placed on high-fat diet before either sham or VSG surgery (N = 12, 9) and then were monitored for resolution of obesity-related comorbidities.

Results:

VSG was sufficient to reduce weight and adiposity in OVX females in comparison to obese rats (P < 0.001). Glucose tolerance (P < 0.05) was improved in OVX-VSG females with no change in insulin sensitivity. Both circulating (P < 0.01) and hepatic triglyceride (P < 0.01) levels were also reduced after VSG. Liver integrity was improved in OVX-VSG in comparison to OVX-obese as reflected by reduced aspartate aminotransferase levels (P < 0.05). The ability of mitochondria to generate adenosine triphosphate was maintained, and an increase in complex IV may decrease the production of mitochondrial reactive oxygen species.

Conclusions:

Taken together, VSG in OVX rats experience many positive benefits including the resolution of hepatic steatosis that persists in reproductively intact female rats after VSG.
Change in sexual functioning over the menopausal transition: results from the Study of Women's Health Across the Nation
Authors: Avis Nancy E. , Colvin Alicia , Karlamangla Arun S. , Crawford Sybil , Hess Rachel , Waetjen L. Elaine , Brooks Maria , Tepper Ping G. , Greendale Gail A.
Published: November 2016

Objective:

The aim of the study was to identify whether there is a decline in sexual functioning related to the menopausal transition or to hysterectomy.

Methods:

In a cohort of 1,390 women aged 42 to 52, with intact uterus and at least one ovary, not using hormone therapy, and pre- or early perimenopausal at baseline, we fit piecewise linear growth curves to 5,798 repeated measurements (seven visits spanning 14.5 y) of a sexual functioning score (range, 5-25) as a function of time relative to date of final menstrual period (FMP) or hysterectomy.

Results:

Mean sexual functioning at baseline in women with a dateable FMP was 18.0 (SD, 3.4). There was no change in sexual function until 20 months before the FMP. From 20 months before until 1 year after the FMP, sexual function decreased by 0.35 annually (95% CI, −0.44 to −0.26) and continued to decline more than 1 year after the FMP, but at a slower rate (−0.13 annually, 95% CI, −0.17 to −0.10). The decline was smaller in African Americans and larger in Japanese than whites. Vaginal dryness, lubricant use, depressive symptoms, or anxiety did not explain decline in sexual function. Women who had a hysterectomy before the FMP did not show a decline in sexual function before hysterectomy, but scores declined afterward (0.21 annually, 95% CI, −0.28 to −0.14).

Conclusions:

Decline in sexual function became apparent 20 months before FMP and slowed 1 year after FMP through 5 years afterward. A decline in sexual function was observed immediately after hysterectomy and persisted for the 5 years of observation.
Bald Spot on the Scalp
Authors: So Jessica Kim , Jacob Sharon E.
Published: November 2016

Teledermatology is a term to describe the provision of dermatologic medical services through telecommunication technology. In this modality, there is transfer of patient medical information electronically (including history and visual data) obtained in one location to a provider who is in another location (Roman & Jacob, 2015). The construct of this column is such that cases are presented in a standardized teledermatology reader format. This is a case of a bald spot on the scalp.
Effect of Differential Enteral Protein on Growth and Neurodevelopment in Infants <1500 g
Authors: Dogra Shivani , Thakur Anup , Garg Pankaj , Kler Neelam
Published: November 2016

Objective:

The aim of the study was to determine whether higher enteral protein intake leads to improved head growth at 40 weeks postmenstrual age (PMA) in preterm infants <32 weeks or 1500 g.

Methods:

Randomized controlled trial in which 120 infants were assigned to either group A with higher enteral protein intake achieved by fortification with higher protein containing fortifier (1 g/100 mL expressed breast milk) or to group B with lower enteral protein intake where fortification was done with standard available protein fortifier (0.4 g /100 mL expressed breast milk).

Results:

The mean (standard deviation) protein intake was higher in group A as compared to group B; 4.2 (0.47) compared with 3.6 (0.37) g · kg−1 · day−1, P < 0.001. At 40 weeks PMA, the mean (standard deviation) weekly occipitofrontal circumference gain was significantly higher in group A as compared to group B; 0.66 (0.16) compared with 0.60 (0.15) cm/week (mean difference 0.064, 95% confidence interval [0.004–0.123], [P = 0.04]). Weight growth velocity in group A was 11.95 (2.2) g · kg−1 · day−1 as compared to 10.78 (2.6) g · kg−1 · day−1 in group B (mean difference 1.10, 95% confidence interval [0.25–2.07], [P = 0.01]). No difference was observed in the length between the 2 groups. There was no difference in growth indices and neurodevelopmental outcomes at 12 to 18 months corrected age in the 2 groups.

Conclusions:

Fortification of expressed human milk with fortifier containing higher protein results in better head growth and weight gain at 40 weeks PMA in preterm infants <32 weeks or 1500 g without any benefits on long‐term growth and neurodevelopment at 12 to 18 months corrected age (CTRI/2014/06/004661).
Designing and Testing an End-of-Life Discussion Intervention for African American Patients With Heart Failure and Their Families
Authors: Piamjariyakul Ubolrat , Smith Carol E. , Werkowitch Marilyn , Thompson Noreen , Fox Maria , Williamson Karin Porter , Olson Lori
Published: November 2016

There is an escalating prevalence of heart failure (HF) with high mortality. Compared with other races, African Americans face a higher incidence of HF at earlier age of onset, with more rapid progression, and with increased family care burden and greater care costs and disparity in health care services at the end of life (EOL). Concomitant out-of-pocket HF costs and care demands indicate the need for early discussion of palliative and EOL care needs. We therefore developed and pilot tested a culturally sensitive intervention specific to the needs of African American HF patients and their families at the EOL. Our pilot study findings encompass patient and caregiver perspectives and align with the state of EOL science. The ultimate long-term goal of this intervention strategy is to translate into practice the preferred, culturally sensitive, and most cost-efficient EOL care recommendations for HF patients and families.
The Impact of Health Literacy on Palliative Care Outcomes
Authors: Christensen Deborah
Published: November 2016

Limited health literacy is a recognized health problem often leading to poorer health outcomes. Health care professionals, including nurses, are responsible for delivering health information in a clear and understandable way. Yet nurses may overestimate patients’ health literacy and miss opportunities to help patients understand and then incorporate medical information. Health outcomes may improve when nurses recognize potential barriers to health literacy and use evidence-based interventions. A review of current research regarding health literacy is provided to assist nurses with communication strategies in their delivery of palliative care.
Care for Dying Patients at Midlife
Authors: Kaup Jaana , Höög Lina , Carlsson Maria E.
Published: November 2016

The aim of the study was to highlight nurses’ experiences of caring for patients in palliative care at midlife, and describe their coping strategies. This study used a qualitative methodology with an inductive and an abductive approach. The analysis started with systematic text condensation. Later in the analysis, an abductive profile inspired by the concepts of a “tentative coping model for nurses in cancer care” was used. Fourteen participants, from 3 specialized palliative home care teams, were interviewed in 3 focus groups. Three themes and 9 codes represented the participants’ experiences and coping strategies: experiences of significances: participants felt admiration for the patients, they became invigorated by their encounters with their patients, and they got confirmation that they did well; stress: participants described how they were affected by external influences, psychological stress, and stress-related symptoms; and coping: participants described the various individual-, group-, and organizational-level coping strategies they used in their daily work and the formal and informal support they received. Based on their descriptions, palliative care nursing was stressful for the nurses. They had various coping strategies and significances that helped them care for the families in the most difficult situations. The study also revealed how important formal support was to the nurses.
You Won't Get Me
Authors: Frühauf Sarah , Figlioli Patrick , Caspar Franz
Published: November 2016

In psychotherapy, therapist and patient influence each other constantly. We aimed to investigate how therapists respond to patient impression management and influence tactics. For 60 videotaped intake interviews, judges rated therapist responses to patient tactics as neutral, desired, or undesired from the patient perspective. Judges rated the therapist responses in 57% as neutral, in 40% as desired, and in 2% as undesired by the patients. The proportions of response outcomes varied across tactics. Therapist responses were unrelated to therapist and patient sex. Therapist experience was related to their responses to the tactic Supplication. Overall, some patient tactics seem to be more challenging for therapists than others. Awareness of such response tendencies can help therapists prepare their reactions to certain patient impression management and influence tactics. Implications for training and research are presented.
Pilot Study of an Exercise Intervention for Depressive Symptoms and Associated Cognitive-Behavioral Factors in Young Adults With Major Depression
Authors: Nasstasia Yasmina , Baker Amanda L. , Halpin Sean A. , Lewin Terry J. , Hides Leanne , Kelly Brian J. , Callister Robin
Published: November 2016

This study assesses the feasibility of integrating motivational interviewing (MI) with an exercise intervention. It also explores patterns of depressive symptom changes (cognitive, affective, and somatic subscales) and their relationship to cognitive, behavioral, and immunological factors (interleukin 6, IL-6, a marker for inflammation) across the exercise intervention. Twelve young adults (20.8 ± 1.7 years) meeting DSM-IV criteria for major depressive disorder received a brief MI intervention followed by a 12-week exercise intervention. Assessments were conducted preintervention, postintervention, throughout the intervention, and at follow-up. Preliminary results show differential effects of exercise, with the largest standardized mean improvements for the affective subscale (−1.71), followed by cognitive (−1.56) and somatic (−1.39) subscales. A significant relationship was observed between increased behavioral activation and lower levels of IL-6. Despite study limitations, the magnitude of changes suggests that natural remission of depressive symptoms is an unlikely explanation for the findings. A randomized controlled trial has commenced to evaluate effectiveness of the intervention.
Should We Treat a Patient’s Symptoms or Angiography Image in TIA?
Authors: Karpatová Hana , Jankových Jana , Mikulík Robert
Published: November 2016

Objectives:

Data on vascular status in the first hours after onset of transient ischemic attack (TIA) and its clinical significance are missing. Also, it is not known whether arterial occlusion, if present in TIA, should be the target for revascularization. We present 2 patients to demonstrate that TIA can be due to acute major intracranial arterial occlusion and to show how such arterial occlusion may affect the outcome.

Case reports:

Two patients (54 and 63 years old) were diagnosed with TIA and at the same time had occlusion of the middle cerebral artery. No recanalization therapy was performed, as there was no or minimal neurological deficit. After several hours, the condition of both patients clinically deteriorated. One patient experienced spontaneous recanalization in the first 24 hours and clinical improvement over the subsequent days, resulting in complete resolution of the neurological deficit. The other patient did not recanalize and developed a significant brain infarction as well as hemorrhagic transformation requiring decompression surgery. Over the long term, the patient remained hemiplegic, unable to walk, and dependent on assistance for most activities of daily living.

Conclusions:

The cases presented here raise important questions: (1) How frequently is arterial occlusion present in clinically asymptomatic patients? (2) If occlusion is present but not symptoms, is stroke a more correct diagnosis than TIA? and (3) What would be the benefit of recanalization therapy? Studies addressing these questions should be conducted.
Adult-onset Opsoclonus-Myoclonus Syndrome Associated With Ganglionic Acetylcholine Receptor Autoantibody
Authors: Galli Jonathan R. , Clardy Stacey L. , Paz Soldán M. Mateo
Published: November 2016

Introduction:

Opsoclonus-myoclonus syndrome (OMS) may have a toxin induced, parainfectious, or paraneoplastic etiology. Several autoantibodies have been associated with adult-onset OMS, most commonly antineuronal nuclear antibody 2 (Ri), and it is most frequently associated with breast or small cell lung cancer. The nicotinic ganglionic acetylcholine receptor autoantibody (α3-AChR Ab) has not been described in association.

Case Report:

A 46-year-old woman was evaluated for symptoms of oscillopsia, tremor, gait imbalance, and mild cognitive deficits that began 6 weeks prior. Neurological examination demonstrated opsoclonus, myoclonus, and mild gait ataxia. Laboratory evaluation revealed an elevated α3-AChR Ab at 0.27 nmol/L (normal ≤0.02 nmol/L) with no other autoantibodies or infectious etiology detected. Thorough screening revealed no evidence of associated malignancy. Immunotherapy with weekly methylprednisolone led to significant improvement.

Conclusions:

This first reported case of α3-AChR Ab positivity in the setting of adult-onset OMS expands the spectrum of associated autoantibodies. The mechanism of disease may be linked to cholinergic nuclei within the brainstem. This case suggests including α3-AChR Ab in the evaluation of adult-onset OMS, and highlights the importance of further understanding α3-AChR within the brain.
EGFR Mutational Profiling in Non–Small Cell Lung Cancer: The Clinical Performance of a Sensitive Reverse-Hybridization Assay
Authors: Kriegshäuser Gernot , Enko Dietmar , Novy Michael , Reitmayr Anita , Loidl Almute , Halwachs-Baumann Gabriele , Oberkanins Christian
Published: November 2016

In patients with non–small cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) mutations have been associated with the tumor response to targeted therapy with EGFR tyrosine kinase inhibitors. Although labor intensive and not very sensitive (ie, an analytical sensitivity of 20%), direct sequencing is widely used for mutation detection. This study aimed at evaluating the potential of a test strip-based reverse-hybridization assay (EGFR StripAssay), designed for the simultaneous detection of 16 mutations in exons 18 to 21 of the EGFR gene, to sensitively identify EGFR mutation in DNA from NSCLC tissue samples. Formalin-fixed paraffin-embedded (FFPE) DNA samples from 59 patients with a histologically confirmed primary NSCLC tumor were used to compare the performance of the EGFR StripAssay against that of the Sanger sequencing. The EGFR StripAssay analysis identified 7 (11.8%) of 59 FFPE samples to carry an EGFR mutation, of which 4 (57.1%) and 3 (42.8%) samples were positive for exon 19 and 21 mutations, respectively. Of note, no sample was identified with EGFR exon 18 or 20 mutation. All mutations were confirmed by DNA sequencing. Using 50 ng of template DNA, the EGFR StripAssay demonstrated a detection limit of 1% mutant sequence in a background of normal DNA. The EGFR StripAssay is a fast and robust platform for the sensitive detection of EGFR mutation in FFPE DNA. Therefore, this assay could be considered as an alternative protocol to Sanger sequencing for EGFR mutation testing on limited-quantity samples.
Multifocal Supra and Infratentorial Medulloblastoma in an Adult: Histologic, Immunohistochemical, and Molecular Evaluation of a Rare Case and Review of the Literature
Authors: Saad Ali G. , Balik Vladimir , Parvez Aatif , El Jamal Siraj M.
Published: November 2016

Multifocal medulloblastomas (MMBs) in adults are exceedingly rare with only 5 reported cases to date. Medulloblastoma in adult differ from its childhood counterpart by being more often lateral in location, desmoplastic in morphology, and better in clinical prognosis. Little is known, however, about the characteristic features of MMB. This is particularly true for their molecular profiles. To date, molecular characteristics of multifocal medulloblastoma have been reported only once. Here, we present the second case of multifocal medulloblastoma along with its detailed morphology, imaging features, and molecular profiles with a critical review of the literature. We believe that MMB should be reported in detail to better understand their behavior, characterize their molecular profiles, and establish therapeutic protocols.
The Fallopian Tube Origin and Primary Site Assignment in Extrauterine High-grade Serous Carcinoma: Findings of a Survey of Pathologists and Clinicians
Authors: McCluggage W. Glenn , Hirschowitz Lynn , Gilks C. Blake , Wilkinson Nafisa , Singh Naveena
Published: November 2016

Accumulating recent evidence suggests that the majority of extrauterine high-grade serous carcinomas (HGSCs) do not arise from the ovary as historically accepted but from the distal, fimbrial end of the fallopian tube from a precursor known as serous tubal intraepithelial carcinoma. There has been variable acceptance of this evidence among pathologists and clinicians dealing with “ovarian” cancer and this has resulted in wide variation in the assignment of primary site between different institutions when HGSC involves >1 anatomic site. This has obvious implications for cancer epidemiology, registration, and entry into clinical trials. We undertook a survey of members of several national and international gynecologic pathology and clinical cancer societies with a view to ascertaining the degree of acceptance of the fallopian tube origin of extrauterine HGSC and to explore various aspects regarding site assignment, pathologic sampling, diagnosis, FIGO staging, and reporting of these neoplasms. The results indicate wide acceptance among both pathologists and clinicians of the fallopian tube theory of origin of HGSC (86% pathologists, 92% clinicians), although there is significant variation regarding the perceived importance of assigning a primary site given the limited prognostic and therapeutic significance. Interestingly, clinicians feel it is more important to assign a primary site than pathologists (71% vs. 49%). The survey also indicates widespread acceptance of recently proposed criteria for site assignment in extrauterine HGSC.
Ovarian Epithelial Inclusions With Mucinous Differentiation: A Clinicopathologic Study of 42 Cases
Authors: Seidman Jeffrey D. , Krishnan Jayashree
Published: November 2016

Ovarian epithelial inclusions lined by mucinous epithelium are rare and of uncertain origin. Ovaries containing such inclusions were studied in 42 women. The inclusions were divided into 3 groups: serous epithelial lined with typical ciliated morphology but with distinct basophilic cytoplasmic mucin in some or all of the lining cells, those lined by typical mucinous epithelium, and those lined by a combination of typical mucinous epithelium and serous epithelium. The mean patient age was 61.5 years. Pure mucinous inclusions were found in 27 patients, serous-type inclusions with cytoplasmic mucin in 20, and mixed type in 10. All 3 types of inclusions were found in 1 patient. Two types of inclusions were found in 13. Four patients had associated mucinous neoplasms (1 mucinous cystadenoma, 1 atypical proliferative seromucinous tumor, and 2 seromucinous cystadenomas), and 11 patients (26%) had endometriosis. The fallopian tubes in 4 patients (9.5%) also displayed mucinous metaplasia; this was not significantly different from the 3.1% we found in our previously reported series of unselected tubes from the same population. These findings suggest that mucinous inclusions may arise as a direct metaplastic change in serous-type inclusions. Other possible origins of mucinous inclusions in the ovarian cortex include endometriosis and Brenner (transitional cell) nests. Whether such inclusions can be a source of mucinous ovarian neoplasms as are Brenner tumors and mature cystic teratomas is unknown and may warrant further investigation.
Endometrial Stromal Sarcoma Arising in Colorectal Endometriosis
Authors: Kilzieh Rania , Rakislova Natalia , Torné Aureli , Salvador Rafael , Nadal Alfons , Ordi Jaume , Saco Adela
Published: November 2016

The malignant transformation of endometriosis is very uncommon. Whereas 75% of tumors arising from endometriosis arise in the ovary, location in extra-genital organs is rare and mesenchymal neoplasms are exceptional. A 47 year-old woman who underwent hysterectomy with bilateral salpingo-ooforectomy due to endometriosis 13 years before presented with abdominal pain. The magnetic resonance imaging (MRI) showed a 9.7×7.5 cm solid-cystic supravesical mass and a recto-vaginal tumor, as well as endometriotic nodules in the sigma, right parametrium and peritoneum that had significantly increased in size over a six months period. The patient underwent surgical resection of the masses. The histological study showed a low-grade endometrial stromal sarcoma (ESS) arising from endometriosis located at recotovaginal septum and affecting colonic wall and multiple peritoneal and pelvic implants. The patient received radiotherapy and aromatase inhibitors and is free of disease after a follow up of 2 years. Only 15 cases of ESS arising in endometriosis of the bowel have been reported. Tumor dissemination at diagnosis is unusual but does not imply a poor prognosis, as only one patient has died due to progression of the tumor. ESS should be included in the differential diagnosis of mesenchymal neoplasms in the intestine.
Raman spectroscopic analysis of archaeological specimens from the wreck of
HMS Swift
, 1770
Authors: Edwards Howell G. M. , Elkin Dolores , Maier Marta S.
Published: November 2016

Specimens from underwater archaeological excavations have rarely been analysed by Raman spectroscopy probably due to the problems associated with the presence of water and the use of alternative techniques. The discovery of the remains of the Royal Navy warship
HMS Swift
off the coast of Patagonia, South America, which was wrecked in 1770 while undertaking a survey from its base in the Falkland/Malvinas Islands, has afforded the opportunity for a first-pass Raman spectroscopic study of the contents of several glass jars from a wooden chest, some of which had suffered deterioration of their contents owing to leakage through their stoppers. From the Raman spectroscopic data, it was possible to identify organic compounds such as anthraquinone and copal resin, which were empirically used as
materia medica
in the eighteenth century to treat shipboard diseases; it seems very likely, therefore, that the wooden chest belonged to the barber-surgeon on the ship. Spectra were obtained from the wet and desiccated samples, but several samples from containers that had leaked were found to contain only minerals, such as aragonite and sediment.

This article is part of the themed issue ‘Raman spectroscopy in art and archaeology’.
The preservation of archaeological brain remains in a human skeleton
Authors: O'Connor Sonia , Edwards Howell G. M. , Ali Esam M. A.
Published: November 2016

The identification of biomass within the cranial cavity of a waterlogged human skeleton inside a fish-tailed wooden coffin from a nineteenth century burial has been confirmed as brain tissue. A comparison is made between the Raman spectra obtained in the current study with those from an Iron Age brain found in an isolated cranium dating from about 500 years BCE, the only other Raman spectroscopy study made of human brain recovered from waterlogged, archaeological excavations. The spectra give some surprisingly detailed information about the state of preservation of brain tissue in both burials, especially when it is realized that, unlike preserved bog bodies, no other soft tissue has survived. The biosignatures of proteinaceous brain material are well characterized. The presence of spectral signatures from extraneous cyanobacterial colonization in the depositional site of the Iron Age brain had been construed to be responsible in part for the unusual preservation of brain tissues in the waterlogged environment, but they were not detected in the current study of the nineteenth century brain. The challenges for Raman spectroscopic analysis of biomaterials under these conditions are reviewed in the light of the successful outcome of the experiments.

This article is part of the themed issue ‘Raman spectroscopy in art and archaeology’.
EuMicrobedbLite: A lightweight genomic resource and analytic platform for draft oomycete genomes
Authors: Panda Arijit , Sen Diya , Ghosh Arup , Gupta Akash , Malar C Mathu , Mishra Gyan Prakash , Singh Deeksha , Ye Wenwu , Tyler Brett M. , Tripathy Sucheta
Published: November 2016

We have developed EuMicrobedbLite A light weight comprehensive genome resource and sequence analysis platform for oomycete organisms. EuMicrobedbLite is a successor of the VBI Microbial Database (VMD) that was built using the Genome Unified Schema (GUS). In this version, the GUS schema has been greatly simplified with removal of many obsolete modules and redesign of others to incorporate contemporary data. Several dependencies such as perl object layers used for data loading in VMD have been replaced with independent light weight scripts. EumicrobedbLite now runs on a powerful annotation engine developed at our lab called Genome Annotator Lite. Currently this database has 26 publicly available genomes and 10 EST datasets of oomycete organisms. The browser page has dynamic tracks presenting comparative genomics analyses, coding and non-coding data, tRNA genes, repeats and EST alignments. In addition, we have defined 44,777 core conserved proteins from twelve oomycete organisms that form 2974 clusters. Synteny viewing is enabled by incorporation of the Genome Synteny Viewer (GSV) tool. The user interface has undergone major changes for ease of browsing. Queryable comparative genomics information, conserved orthologous genes and pathways are among the new key features updated in this database. The browser has been upgraded to enable user upload of GFF files for quick view of genome annotation comparisons. The toolkit page integrates the EMBOSS package and has a gene prediction tool. Annotations for the organisms are updated once every six months to ensure quality. The database resource is available at www.eumicrobedb.org.
Bayesian mapping reveals that attention boosts neural responses to predicted and unpredicted stimuli
Authors: Garrido M. I. , Rowe E. G. , Halász Veronika , Mattingley J. B.
Published: November 2016

Predictive coding posits that the human brain continually monitors the environment for regularities and detects inconsistencies. It is unclear, however, what effect attention has on expectation processes, as there have been relatively few studies and the results of these have yielded contradictory findings. Here, we employed Bayesian model comparison to adjudicate between two alternative computational models. TheOppositionmodel states that attention boosts neural responses equally to predicted and unpredicted stimuli, whereas theInteractionmodel assumes that attentional boosting of neural signals depends on the level of predictability. We designed a novel, audiospatial attention task that orthogonally manipulated attention and prediction by playing oddball sequences in either the attended or unattended ear. We observed sensory prediction error responses, with electroencephalography, across all attentional manipulations. Crucially, posterior probability maps revealed that, overall, theOppositionmodel better explained scalp and source data, suggesting that attention boosts responses to predicted and unpredicted stimuli equally. Furthermore, Dynamic Causal Modelling (DCM) showed that theseOppositioneffects were expressed in plastic changes within the mismatch negativity network. Our findings provide empirical evidence for a computational model of the opposing interplay of attention and expectation in the brain.
Power calculator for instrumental variable analysis in pharmacoepidemiology
Authors: Walker Venexia M , Davies Neil M , Windmeijer Frank , Burgess Stephen , Martin Richard M
Published: November 2016

Background

Instrumental variable analysis, for example with physicians’ prescribing preferences as an instrument for medications issued in primary care, is an increasingly popular method in the field of pharmacoepidemiology. Existing power calculators for studies using instrumental variable analysis, such as Mendelian randomisation power calculators, do not allow for the structure of research questions in this field. This is because the analysis in pharmacoepidemiology will typically have stronger instruments and detect larger causal effects than in other fields. Consequently, there is a need for dedicated power calculators for pharmacoepidemiological research.

Methods and results

The formula for calculating the power of a study using instrumental variable analysis in the context of pharmacoepidemiology is derived before being validated by a simulation study. The formula is applicable for studies using a single binary instrument to analyse the causal effect of a binary exposure on a continuous outcome. A web application is provided for the implementation of the formula by others.

Conclusions

The statistical power of instrumental variable analysis in pharmacoepidemiological studies to detect a clinically meaningful treatment effect is an important consideration. Research questions in this field have distinct structures that must be accounted for when calculating power.

FUNDING STATEMENT

This work was supported by the Perros Trust and the Integrative Epidemiology Unit. The Integrative Epidemiology Unit is supported by the Medical Research Council and the University of Bristol [grant number MC_UU_12013/9]. Stephen Burgess is supported by a post-doctoral fellowship from the Wellcome Trust [100114].

Key Messages

Research questions using instrumental variable analysis in pharmacoepidemiology have distinct structures that have previously not been catered for by instrumental variable analysis power calculators.

Power can be calculated for studies using a single binary instrument to analyse the causal effect of a binary exposure on a continuous outcome in the context of pharmacoepidemiology using the presented formula and online power calculator.

The use of this power calculator will allow investigators to determine whether a pharmacoepidemiology study is likely to detect clinically meaningful treatment effects prior to the study’s commencement.
Enterovirus A119 in a child with Acute Flaccid Paralysis, Nigeria
Authors: Adeniji JA , Oragwa AO , George UE , Ibok UI , Faleye TOC , Adewumi MO
Published: November 2016

The oldest EV-A119 record was in 2008 in a chimpanzee in Cameroon and subsequently in more non-human primates and healthy children. Here we report for the first time the detection of EV-A119 in a child with Acute Flaccid Paralysis, thus suggesting possible association with a clinical condition in humans.
Chromosome interactome inferred from mitosis-G1 transition
Authors: Eidelman Y.A. , Slanina S.V. , Aleshchenko A.V. , Andreev S.G.
Published: November 2016

The progress in experimental techniques aimed at 3D genome study is yet to bring about revelation of basic principles of genome folding. Chromosome conformation capture Hi-C technologies provide genome wide mapping of genomic loci interactions but spatial organization of chromosomes remains unknown. Here, we develop a polymer modeling approach to generate the ensemble of 3D chromosome conformations for mapping genetic loci contacts and the positions of megabase chromosomal domains in interphase chromosome at different time of mitosis-interphase transition. We demonstrate that (*) whole chromosome contact map (interactome) generated for mouse chromosome 18 structure and (**) contact patterns, observed soon after mitotic decondensation and remaining similar during G1, correlate well with the experimental Hi-C contact data. The results suggest that contact map formation and spatial compartmentalization of an interphase chromosome are driven by interactions between different types of domains during formation of globular chromosome state at the end of mitotis-G1 transition.
Metabolic and spatio-taxonomic response of uncultivated seafloor bacteria following the Deepwater Horizon oil spill
Authors: Handley KM , Piceno YM , Hu P , Tom LM , Mason OU , Andersen GL , Jansson JK , Gilbert JA
Published: November 2016

The release of 700 million liters of oil into the Gulf of Mexico over a few months in 2010 produced dramatic changes in the microbial ecology of the water and sediment. Previous 4 studies have examined the phylogeny and function of these changes, but until now a 5 fundamental examination of the extant hydrocarbon metabolisms that supported these 6 changes had not been performed. Here, we reconstructed the genomes of 57 widespread 7 uncultivated bacteria from post spill sediments, and recovered their gene expression 8 pattern across the seafloor. These genomes comprised a common collection of bacteria 9 that were highly enriched in heavily affected sediments around the wellhead. While rare in distal sediments, some members were still detectable at sites up to 60 km away. Many of these genomes exhibited phylogenetic clustering indicative of common trait selection by the environment, and within half we identified 264 genes associated with hydrocarbon degradation. Observed alkane degradation ability was near ubiquitous among candidate hydrocarbon degraders, while just 3 harbored elaborate gene inventories for the degradation of alkanes and (poly)aromatic hydrocarbons. Differential gene expression profiles revealed a spill-promoted microbial sulfur cycle alongside gene up-regulation associated with polyaromatic hydrocarbon degradation. Gene expression associated with alkane degradation was widespread, although active alkane degrader identities changed along the pollution gradient. The resulting analysis suggests a broad metabolic capacity to respond to oil exists across a large array of usually rare bacteria.
The Dihydrofolate Reductase Protein-Fragment Complementation Assay: A Survival-Selection Assay for Large-Scale Analysis of Protein–Protein Interactions
Authors: Michnick Stephen W. , Levy Emmanuel D. , Landry Christian R. , Kowarzyk Jacqueline , Messier Vincent
Published: November 2016

Protein-fragment complementation assays (PCAs) can be used to study protein–protein interactions (PPIs) in any living cell, in vivo or in vitro, in any subcellular compartment or membranes. Here, we present a detailed protocol for performing and analyzing a high-throughput PCA screening to study PPIs in yeast, using dihydrofolate reductase (DHFR) as the reporter protein. The DHFR PCA is a simple survival-selection assay in which Saccharomyces cerevisiae DHFR (scDHFR) is inhibited by methotrexate, thus preventing nucleotide synthesis and causing arrest of cell division. Complementation of cells with a methotrexate-insensitive murine DHFR restores nucleotide synthesis, allowing cell proliferation. The methotrexate-resistant DHFR has two mutations (L22F and F31S) and is 10,000 times less sensitive to methotrexate than wild-type scDHFR, but retains full catalytic activity. The DHFR PCA is sensitive enough for PPIs to be detected for open reading frame (ORF)-PCA fragments expressed off of their endogenous promoters.
Combining the Dihydrofolate Reductase Protein-Fragment Complementation Assay with Gene Deletions to Establish Genotype-to-Phenotype Maps of Protein Complexes and Interaction Networks
Authors: Diss Guillaume , Landry Christian R.
Published: November 2016

Systematically measuring the impact of gene deletion on protein–protein interactions is a promising approach to reveal the structural bases of protein interaction networks and to allow a better understanding of how genotypes translate into phenotypes. Genetic and protein-interaction tools in yeast now allow us to explore this third dimension of protein–protein interaction networks. Because it is scalable and quantitative, the protein-fragment complementation assay (PCA) using dihydrofolate reductase (DHFR) as the reporter protein provides an exceptionally powerful tool for such a purpose. Here, we describe a fully automated protocol that combines DHFR PCA for protein–protein interaction measurement and synthetic genetic array (SGA) technology for introducing mutant and other alleles into PCA strains using genetic crosses. In this, PCA strains are crossed with strains carrying a gene deletion and SGA markers, and the recombinant haploid progeny are selected by SGA. The resulting haploid strains, each expressing a DHFR-fragment fusion protein in a gene-specific haploid deletion background, are crossed to measure the interaction between the two recombinant proteins by PCA in a diploid homozygous deletion background. This approach can be used to measure a single protein interaction in a large array of genetic backgrounds or a large number of protein interactions in a small number of genetic backgrounds.
Dissecting the Contingent Interactions of Protein Complexes with the Optimized Yeast Cytosine Deaminase Protein-Fragment Complementation Assay
Authors: Ear Po Hien , Kowarzyk Jacqueline , Michnick Stephen W.
Published: November 2016

Here, we present a detailed protocol for studying in yeast cells the contingent interaction between a substrate and its multisubunit enzyme complex by using a death selection technique known as the optimized yeast cytosine deaminase protein-fragment complementation assay (OyCD PCA). In yeast, the enzyme cytosine deaminase (encoded by FCY1) is involved in pyrimidine metabolism. The PCA is based on an engineered form of yeast cytosine deaminase optimized by directed evolution for maximum activity (OyCD), which acts as a reporter converting the pro-drug 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU), a toxic compound that kills the cell. Cells that have OyCD PCA activity convert 5-FC to 5-FU and die. Using this assay, it is possible to assess how regulatory subunits of an enzyme contribute to the overall interaction between the catalytic subunit and the potential substrates. Furthermore, OyCD PCA can be used to dissect different functions of mutant forms of a protein as a mutant can disrupt interaction with one partner, while retaining interaction with others. As it is scalable to a medium- or high-throughput format, OyCD PCA can be used to study hundreds to thousands of pairwise protein–protein interactions in different deletion strains. In addition, OyCD PCA vectors (pAG413GAL1-ccdB-OyCD-F[1] and pAG415GAL1-ccdB-OyCD-F[2]) have been designed to be compatible with the proprietary Gateway technology. It is therefore easy to generate fusion genes with the OyCD reporter fragments. As an example, we will focus on the yeast cyclin-dependent protein kinase 1 (Cdk1, encoded by CDC28), its regulatory cyclin subunits, and its substrates or binding partners.
Chromatin Immunoprecipitation (ChIP) in Schizosaccharomyces pombe
Authors: Cam Hugh P. , Whitehall Simon
Published: November 2016

Chromatin immunoprecipitation (ChIP), the cross-linking of chromatin followed by immunoprecipitation with antibodies against a chromatin target, is a key method for measuring association of proteins with a specific genomic region(s). As a negative control, a mock ChIP experiment in which no antibody is added to the immunoprecipitation reaction is included. Enriched DNA fragments from a ChIP experiment can be analyzed in a variety of ways. For semiquantitative analysis, a region of interest can be amplified using standard polymerase chain reaction (PCR) techniques. PCR products are analyzed on agarose (or polyacrylamide) gels and band intensity calculated with a standard imaging software. ChIP enrichment is usually calculated as the ratio of ChIP to input compared with a similar ratio for a reference region not expected to be enriched for that factor. For heterochromatin analysis, housekeeping genes such as act1+ are good references. Real-time quantitative PCR (qPCR) can be used for a fully quantitative approach. If a factor is to be mapped across the genome, ChIP DNA can be amplified and labeled for microarray analysis or scrutinized on a next-generation DNA sequencing platform.
Visualizing Genomic Annotations with the UCSC Genome Browser
Authors: Hung Jui-Hung , Weng Zhiping
Published: November 2016

Genomic data and annotations are rapidly accumulating in databases such as the UCSC Genome Browser, NCBI, and Ensembl. Given the massive scale of these genomic databases, it is important to be able to easily retrieve known data and annotations of a specified genomic locus. For example, for a newly identified cis-regulatory element bound by a transcription factor, questions that immediately come to mind include whether the element is near a transcriptional start site and, if so, the name of the corresponding gene, and whether the histones or DNA at the locus are modified. The UCSC Genome Browser organizes data and annotations (called tracks) around the reference sequences or draft assemblies of many eukaryotic genomes and presents them using a powerful web-based graphical interface. This protocol describes how to use the UCSC Genome Browser to visualize selected tracks at specified genomic regions, download the data and annotations for further analysis, and retrieve multiple sequence alignments and their conservation scores.
Transcription Factor–DNA Binding Motifs in Saccharomyces cerevisiae: Tools and Resources
Authors: Schipper Joshua L. , Gordân Raluca M.
Published: November 2016

The DNA binding specificity of transcription factors (TFs) is typically represented in the form of a position weight matrix (PWM), also known as a DNA motif. A PWM is a matrix that specifies, for each position in the DNA binding site of a TF, the “weight” or contribution of each possible nucleotide. DNA motifs can be derived from various types of TF–DNA binding data, from small collections of known TF binding sites to large data sets generated using high-throughput technologies. One drawback of this simple model of DNA binding specificity is that it makes the implicit assumption that individual base pairs within a TF binding site contribute independently to the TF–DNA binding affinity. Although this assumption does not always hold, PWM models have been shown to provide reasonable approximations to the DNA binding specificity, and they are still widely used in practice. DNA motifs are currently available for more than 150 Saccharomyces cerevisiae TFs. Here, we briefly describe how these models are built, we provide information on databases containing DNA motifs for S. cerevisiae TFs, and we introduce guidelines on how to interpret the motifs and use them in practice to generate hypotheses about transcriptional regulatory regions.
Cost analysis of rice milling: a case study of 7 rice mills in Malaysia
Authors: Chung Bonhee , Arshad Fatimah Mohamed , Noh Kusairi Mohd , Sidique Shaufique Fahmi
Published: November 2016

Purpose

The purpose of this paper is to examine the long-run profitability of rice milling operation in Malaysia and see how sensitive it is to changes in paddy purchases, rice recovery ratio and paddy price.

Design/methodology/approach

Using a purposive sampling technique and semi-structured interviews, seven rice mills in Malaysia were selected to obtain data on operational details and business accounts. The paper provides a qualitative and descriptive account of the rice mill’s profitability by using cost curves, a simple linear regression and the Monte Carlo simulation.

Findings

The rice milling operation in Malaysia is profitable in the long run, provided that there is a market for by-products. Large private mills have lower average costs, helping them obtain higher profit margins. Public mills that receive a rice miller subsidy are more protected than small private mills that operate without the rice miller subsidy and under price controls. Changes in paddy purchases, paddy price and recovery ratio affect the profitability to varying degrees.

Research limitations/implications

Incomplete information provided by the interviewees. The analysis result is only a rough estimate. However, it may provide a useful insight into the Malaysian rice milling sector and its competitiveness.

Originality/value

There are few economic studies of the rice milling sector in Malaysia. However, it plays an important role along the rice supply chain. There is a need for better understanding of the industry in order to obtain economic sustainability and effective policies. This paper provides the gap by providing an insight into the long-run profitability of rice milling operation in Malaysia.
Adoption of African indigenous vegetables into agro-pastoral livelihoods for income and food security
Authors: Mshenga Patience Mlongo , Saidi Mwanarusi , Nkurumwa Agnes O. , Magogo Juma Riziki , Oradu Shem Ipomai
Published: November 2016

Purpose

The purpose of this paper is to determine the factors influencing adoption of African indigenous vegetables (AIVs) into the agro-pastoral farming systems aiming at improving livelihoods.

Design/methodology/approach

The paper is based upon the diffusion theory which is linked to the random utility theory. A survey of 205 agro-pastoral households obtained through multistage sampling technique was used. Factors influencing adoption of AIVs were estimated using a logit model.

Findings

Findings indicate that the acreage under AIVs was still very low compared to other crop enterprises with the most common types of AIVs grown being Solanum nigrum, Amaranthus spp., Cucurbita maxima, Vigna unguiculata, Basella alba and Cleome gynandra. Factors influencing adoption were found to be gender, age, farm size, education level, off-farm income and number of visits to extension officer.

Research limitations/implications

Limitations include reliance on respondents’ willingness to provide correct information.

Originality/value

This paper adds value in its contribution to literature on diversifying agro-pastoral livelihoods through production of AIVs for income and food security.