bluuebunny/crossref_metadata_2025 huggingface dataset:
Accuracy of p57KIP2 compared with genotyping to diagnose complete hydatidiform mole: a systematic review and meta‐analysis
Authors: Madi JM , Braga A , Paganella MP , Litvin IE , Wendland EM
Published: May 2018

Background

Distinguishing hydatidiform moles (HMs) from nonmolar specimens and the subclassification of HM are important because complete hydatidiform mole (CHM) is associated with an increased risk of development of gestational trophoblastic neoplasia. However, diagnosis based solely on morphology has poor inter‐observer reproducibility. Recent studies have demonstrated that the use of p57KIP2 immunostaining improves diagnostic accuracy for CHM.

Objectives

To evaluate the accuracy of p57KIP2 immunostaining compared with molecular genotyping for the diagnosis of CHM.

Search strategy

Major databases were searched from inception to March 2017 using the terms ‘hydatidiform mole’, ‘p57’, and ‘genotyping’, with their variations, and the search limit for the relevant study design.

Selection criteria

Any cross‐sectional study, case series, case–control study, cohort study, or clinical trial that evaluated the accuracy of p57KIP2 immunostaining for the diagnosis of CHM compared with genotyping was included. Case reports, narrative reviews, expert opinions, and animal testing were excluded.

Data collection and analysis

Extracted accuracy data were tabulated and pooled using a hierarchical bivariate random effects model.

Main results

Bivariate meta‐analysis produced a summary sensitivity of 0.984 (95% CI: 0.916–1.000) and specificity of 0.625 (95% CI: 0.503–0.736) with significant heterogeneity for specificity (I2 = 71.8, chi‐square P = 0.029). The pooled summary diagnostic odds ratio was 56.54 (95% CI: 11.03–289.74) with no heterogeneity (I2 = 0.00%, chi‐square P = 0.67). The diagnostic performance of the test was high with an area under the curve of (AUC) 0.980.

Conclusions

p57KIP2 immunostaining is accurate when diagnosing CHM. It can be used as an adjunct test in a combination algorithmic approach.

Tweetable abstract

A meta‐analysis to evaluate the accuracy of p57KIP2 compared with genotyping to diagnose CHM.
The Relationship between Costs and Quality in Veterans Health Administration Community Living Centers: An Analysis Using Longitudinal Data
Authors: Burgess James F. , Shwartz Michael , Stolzmann Kelly , Sullivan Jennifer L.
Published: May 2018

Objective

To examine the relationship between cost and quality in Veterans Health Administration (VA) nursing homes (called Community Living Centers, CLCs) using longitudinal data.

Data Sources/Study Setting

One hundred and thirty CLCs over 13 quarters (from FY2009 to FY2012) were studied. Costs, resident days, and resident severity (RUGs score) were obtained from the VA Managerial Cost Accounting System. Clinical quality measures were obtained from the Minimum Data Set, and resident‐centered care (RCC) was measured using the Artifacts of Culture Change Tool.

Study Design

We used a generalized estimating equation model with facilities included as fixed effects to examine the relationship between total cost and quality after controlling for resident days and severity. The model included linear and squared terms for all independent variables and interactions with resident days.

Principal Findings

With the exception of RCC, all other variables had a statistically significant relationship with total costs. For most poorer performing smaller facilities (lower size quartile), improvements in quality were associated with higher costs. For most larger facilities, improvements in quality were associated with lower costs.

Conclusions

The relationship between cost and quality depends on facility size and current level of performance.
Post‐operative stereotactic radiotherapy for the treatment of intracranial haemangiopericytoma: ‘A Study of Dose and Outcome’
Authors: Nair Rohan , Panettieri Vanessa , Chang Joe H , Dally Michael
Published: May 2018

Introduction

This study was performed to assess the relationship between tumour response and radiation dose in equivalent 2 Gy per fraction (EQD2).

Method

A retrospective cohort analysis of 21 patients with a diagnosis of intracranial haemangiopericytoma between 2000 and 2013 was included in this study. A total of 39 lesions were analysed. The equivalent dose in 2 Gy per fraction was calculated by assigning an alpha–beta ratio of 12 Gy. A paired t‐test compared dose (EQD2) and tumour response, and as the outcome was binary, a logistic regression analysis was performed.

Results

In total, there were 14 cases of progression and 25 cases of non‐progression. It was estimated that for a one unit increase in EQD2, the odds of non‐progression were increased by a factor of 1.13 (P = 0.026). After adjusting for PTV volume, the estimated effect of EQD2 (min) on tumour response was stronger, with an estimated odds ratio of 1.36 for an increase of one unit and an odds ratio of 21.6 for an increase of 10 units (P = 0.015). The dose range varied with varying PTV volumes. Based on the logistic model, the probability of having non‐progression is larger than 50% for EQ2Dmin doses larger than 30–40 Gy, in particular for volumes larger than 3.67 cm3.

Conclusion

This study demonstrates that there is a relationship between dose (EQD2) and outcome. With increasing dose, the likelihood of regression is higher. When adjusted for PTV volume, the response appeared stronger. The dose varied significantly with changes in the size of the PTV.
Sustainability of the accounting and finance academic profession: students’ and supervisors’ views about the PhD supervision process
Authors: Unda Luisa A. , Khosa Amrinder , Burch Steven , Wilkin Carla
Published: May 2018

This study explores the research supervisory practices of accounting and finance PhD students at Australian and New Zealand universities. Given documented faculty shortages in the accounting and finance disciplines, such investigation is timely and relevant. In the context of student engagement with their community of academic practice and their intrinsic motivation related to individual competence and autonomy, situational adjustments are inevitable and explain some differences between students’ perceptions and supervisors’ expectations. Our findings demonstrate that, despite general satisfaction with the PhD supervision process, students articulated concerns regarding constructive feedback and pastoral care provided by their supervisors, as well as guidance regarding data analysis/statistics.
Bat activity before and after a severe wildfire in Pilliga forests: Resilience influenced by fire extent and landscape mobility?
Authors: Law Bradley , Doty Anna , Chidel Mark , Brassil Traecey
Published: May 2018

Wildfires are becoming increasingly severe and common in many parts of the world, yet their effects on certain taxa remain poorly studied. In November 2006, a major wildfire occurred in the Pilliga forests of north‐west New South Wales, Australia. This fire was severe and extensive, burning more than 120 000 ha. Prior to the fire, we conducted a study in the affected area assessing bat activity in relation to flyway size and riparian zones, allowing us to opportunistically compare before – and – after effects of wildfire on bats in burnt and unburnt areas. We assessed how bat activity and bat composition changed from 1 year pre‐fire to 1 year post‐fire and 4 years post‐fire, accounting for the effects of flyway size. A BACI analysis showed that there was an effect of time (year) on bat activity, with activity markedly reduced in both burnt and unburnt sites in the year post‐ fire, before recovering 4‐years post‐fire to levels that approached pre‐burn activity. However, there was no treatment or interaction effect, indicating fire alone did not affect bat activity at our sites. Activity was 50% lower at supplementary sites more remote (~5 km) from the fire edge. Multi‐dimensional scaling and permanova described a strong effect of year but no evidence of fire or stream size‐mediated effects on species composition. The drop in activity post‐fire coincided with a period of drought that subsequently broke in the year prior to our survey 4 years post‐fire. Some species‐specific responses to the fire were evident and depended on the proximity to unburnt forest. We suggest the potential for landscape re‐assortment, whereby some species may move from the unburnt landscape into the burnt landscape, possibly in response to a resource pulse of insects. A landscape pattern of movement could obscure the detection of direct fire effects on mobile bats. We suggest fire extent, proximity to unburnt vegetation and severity are key considerations when interpreting the response of bats to wildfire.
Changes in bird assemblages in a wetland ecosystem after 14 years of intensified cattle farming
Authors: Sica Yanina V. , Gavier‐Pizarro Gregorio I. , Pidgeon Anna M. , Travaini Alejandro , Bustamante Javier , Radeloff Volker C. , Quintana Rubén D.
Published: May 2018

Human activities have modified wetlands all over the word. Water control structures that are frequently implemented in these ecosystems to keep lands free of flooding can decrease or degrade habitat for biodiversity. The Paraná River Delta, one of the largest wetlands in Argentina, has recently experienced rapid cattle grazing intensification facilitated by water control structures, resulting in extensive conversion of wetlands to pastures. It is unclear if this loss of wetlands has had a negative impact on the highly diverse bird community. Here, we evaluated the changes in bird assemblages in the Lower Delta of Paraná River after 14 years of cattle grazing intensification. We compared point count data from 1997 to 1999 with data collected in 2012 and 2013 using the same survey methods. We assessed the temporal changes in bird richness and composition using paired permutation tests and multivariate analysis. We related the bird composition to landscape changes to analyse if avian changes were associated with landscape dynamics. We found that after 14 years, the bird community differed greatly. In general, species richness decreased, especially in wet years. We found fewer wetland species in recent surveys; in particular we did not register saffron‐cowled blackbird (Xanthopsar flavus), a species listed as globally vulnerable. Changes in bird composition were associated with an increase in bare soil due to land‐use changes. Even though inter‐annual differences in precipitation and river stage have great effects on the species present in the surveys, the absence of many wetland species in recent wet years, that is when habitat is suitable for them, is most likely due to changes in land cover. Globally, agricultural land use makes inroads into many wetlands, eroding their quality and extent. Maintenance of wetland species requires that conservation efforts focus on these vulnerable ecosystems before full‐scale land conversion occurs.
IL‐3–producing basophils are required to exacerbate airway hyperresponsiveness in a murine inflammatory model
Authors: Rignault‐Bricard R. , Machavoine F. , Mecheri S. , Hermine O. , Schneider E. , Dy M. , Leite‐de‐Moraes M.
Published: May 2018

Background

Basophils are commonly associated with allergic responses because of their ability to produce large amounts of pro‐Th2 cytokines and histamine. However, the mechanisms through which bone marrow‐resident basophils (BMRB) become fully competent cytokine and histamine producers in response to IgE crosslinking are poorly understood. Here, we sought to determine the role of IL‐3 in promoting pro‐Th2 basophils.

Methods

BMRB and basophils exposed to IL‐3 in vitro and in vivo were evaluated for their production of Th2 cytokines and histamine in response to FcεRI crosslinking on both protein and gene expression levels. In vivo relevance of our findings was assessed in a model of ovalbumin‐induced allergic asthma using IL‐3–deficient and wild‐type mice in a protocol of adoptive basophil transfer.

Results

We show that BMRB and basophils previously exposed to IL‐3 differ in their ability to generate cytokines (IL‐4, IL‐6, IL‐13, and GM‐CSF) and histamine in response to FcεRI crosslinking, reflecting two stages of maturation. Exposure to IL‐3 initiated an autocrine loop of endogenous IL‐3 production that enhanced histamine and cytokine production upon FcεRI crosslinking. This increased responsiveness required calcium flux and was dependent on calcineurin and store‐operated calcium channels. Our findings are of pathophysiological relevance, as assessed by the failure of IL‐3–deficient mice to develop airway hyperreactivity, which could be restored by adoptive transfer of IL‐3–derived basophils recovered from wild‐type mice.

Conclusion

IL‐3–dependent basophils promote Th2 allergic AHR, which designates the IL‐3/basophil axis as a promising therapeutic target for the treatment of basophil‐dependent asthma.
Lifetime number of years of menstruation as a risk index for postmenopausal endometrial cancer in the Norwegian Women and Cancer Study
Authors: Gavrilyuk Oxana , Braaten Tonje , Weiderpass Elisabete , Licaj Idlir , Lund Eiliv
Published: May 2018

Introduction

Lifetime number of years of menstruation (LNYM) reflects a woman's cumulative exposure to endogenous estrogen and can be used as a measure of the combined effect of reproductive factors related to endometrial cancer (EC) risk.

Material and methods

We aimed to study the association between LNYM and EC risk among postmenopausal women and calculate the population attributable fraction of EC for different LNYM categories. Our study sample consisted of 117 589 women from the Norwegian Women and Cancer (NOWAC) Study. All women were aged 30‐70 years at enrollment and completed a baseline questionnaire between 1991 and 2006. Women were followed up for EC to December 2014 through linkages to national registries. We used Cox proportional hazards models to estimate hazard ratios with 95% confidence intervals (95% CIs), adjusted for potential confounders.

Results

In all, 720 women developed EC. We found a statistically significant, positive dose‐response relationship between LNYM and EC, with a 9.1% higher risk for each additional year of LNYM (P for trend < .001). Using the LNYM category ≥40 as a reference, the hazard ratios for LNYM <25, 25‐29, 30‐34, 35‐39 were 0.17 (95% CI 0.22‐0.27), 0.25 (95% CI 0.17‐0.36), 0.43 (95% CI 0.32‐0.58), and 0.68 (95% CI 0.51‐0.92), respectively. The association between LNYM and EC was independent of incomplete pregnancies, menopausal hormone therapy, diabetes, and body mass index. When considering the population attributable fraction, 67% of EC was estimated to be attributable to LNYM ≥25 years.

Conclusions

Our study supports that increasing LNYM is an important and independent predictor of EC risk.
Reducing the number of obstetrical beds by challenging traditions
Authors: Salvig Camilla D. , Storkholm Marie H. , Salvig Jannie D. , Uldbjerg Niels
Published: May 2018

The aim of this commentary is to describe changes in women’s care at an obstetric department that made it possible to reduce the number of beds from 40 to 29. Patient pathways were reviewed and revised using lean methodology. The mean length of stay was reduced from 70 to 59 h and the mean numbers of hospitalizations per woman from 1.26 to 1.20. At the organizational level, we introduced a Family Department, home management of newborns, home monitoring of the women with cardiotocography and blood samples, and intrapartum Group B Streptococcus‐PCR. Additionally, an After Birth Clinic and network meetings for vulnerable women were established. In patient pathway, we reduced the hospitalization indicated by preterm premature rupture of membranes, preeclampsia and observation after birth laceration. According to National Patient Satisfaction surveys, there was no decrease in women’s satisfaction after reducing the number of beds.
Cognitive and functional deficits in bipolar disorder and schizophrenia as a function of the presence and history of psychosis
Authors: Bowie Christopher R , Best Michael W , Depp Colin , Mausbach Brent T , Patterson Thomas L , Pulver Ann E , Harvey Philip D
Published: May 2018

Objectives

Schizophrenia and bipolar disorder overlap considerably. Schizophrenia is a primary psychotic disorder, whereas approximately half of people with bipolar disorder will experience psychosis. In this study, we examined the extent to which cognitive and functional impairments are related to the presence and history of psychosis across the two disorders.

Method

A total of 633 participants with bipolar disorder I, schizophrenia, and schizoaffective disorder were recruited for a study on the genetics of cognition and functioning in bipolar disorder and schizophrenia. Participants were classified into five groups: bipolar disorder with current psychosis (N = 30), bipolar disorder with a history of psychosis (N = 162), bipolar disorder with no history of psychosis (N = 92), schizophrenia with current psychosis (N = 245), and schizophrenia with past psychosis (N = 104).

Results

Cognitive profiles of all groups were similar in pattern; however, both current psychosis (P < .02) and a diagnosis of schizophrenia (P < .03) were associated with greater impairment. Schizophrenia with current psychosis was also associated with a superimposed severe impairment in processing speed. Both psychosis (P < .03) and schizophrenia diagnosis (P < .01) were associated with poorer functional competence. Individuals with bipolar disorder and schizophrenia experienced similar impairments in real‐world functioning if they were experiencing current psychosis (P = .32).

Conclusion

The presence of active psychosis is an important cross‐diagnostic factor in cognition and functioning in both schizophrenia and bipolar disorder. Characterization and treatment of cognition and functional deficits in bipolar disorder should consider the effects of both current and history of psychosis.
Double trouble: Weekend sleep changes are associated with increased impulsivity among adolescents with bipolar I disorder
Authors: Gershon Anda , Johnson Sheri L , Thomas Leigh , Singh Manpreet K
Published: May 2018

Objectives

Both sleep disruption and impulsivity are important predictors of the course of bipolar disorder (BD). Although sleep disruption has been shown to intensify impulsivity, little research has considered how these two important domains interact within BD. Adolescence is a critical period for the onset of BD, and is often associated with increases in impulsivity and substantial changes in sleep. We tested the hypothesis that disruptions in sleep would increase impulsivity among adolescents, and that this effect would be more pronounced among those with BD.

Methods

Thirteen‐ to nineteen‐year‐olds diagnosed with BD‐I (n = 33, age [mean ± standard deviation (SD)] 16.2 ± 1.66 years, 54.5% female) and psychiatrically healthy controls (n = 26, age [mean ± SD] 15.5 ± 1.45 years, 55.6% female) reported their past‐week bedtime, rise time, and sleep duration, separately for school days and weekends, and completed a self‐report questionnaire on impulsivity. Stepwise regression was used to examine the effects of sleep on impulsivity, and the moderation of this effect by BD status.

Results

Adolescents with BD reported significantly higher impulsivity, later and more variable rise time, and more variable time in bed and sleep duration on school days than did controls. Greater change in sleep duration between school days and weekends was associated with significantly more impulsivity among adolescents with BD as compared to controls.

Conclusions

These findings highlight the important effect of sleep on impulsivity among adolescents with BD and add to the growing evidence that establishing sleep routines may be an important therapeutic target for youth with BD.
Guideline of guidelines: bladder pain syndrome
Authors: Malde Sachin , Palmisani Stefano , Al‐Kaisy Adnan , Sahai Arun
Published: May 2018

Objectives

Bladder pain syndrome (BPS) is a debilitating condition which can be difficult to diagnose and treat due to the lack of consensus on aetiology, definition, and management. The aim of this review is to summarise the findings from major national and international guidelines on the management of BPS, highlighting areas of disagreement and uncertainty.

Methods

We performed a Medline/PubMed search from 1st January 2000 to 31st December 2017 in order to identify relevant guidelines addressing BPS/interstitial cystitis. We also manually searched the websites of major national and international societies. The following guidelines were included in this review: European Association of Urology, American Urological Association, International Society for the Study of BPS, International Consultation on Incontinence, International Continence Society, East Asian guideline, Royal College of Obstetricians and Gynaecologists/British Society of Urogynaecology, and the Canadian Urological Association.

Results

There is disagreement between guidelines on the exact definition of BPS and the nomenclature to use to describe this condition. However, all agree that the diagnosis is dependent on the presence of pain, pressure, or discomfort, in addition to at least one urinary symptom, in the absence of other diseases that could cause pain. Exclusion of other pathology that could cause similar symptoms requires thorough evaluation, and is recommended in all guidelines. There is also disparity in the recommended diagnostic investigation of BPS, with hydrodistension and bladder biopsy either recommended, considered optional, or not recommended, by different guidelines. It is accepted that BPS can be diagnosed clinically, without invasive investigation, but cystoscopy and diagnostic hydrodistension aids sub‐typing of patients and may help direct treatment strategies. Patients should be phenotyped in order to direct multimodal treatment (including behavioural, physical, emotional, and psychological therapy), and treatments should follow a stepwise approach starting with the most conservative. Although widely performed, hydrodistension as a therapeutic strategy has a limited evidence base and is unlikely to provide long‐term resolution of symptoms

Conclusion

There are multiple national and international guidelines for the diagnosis and management of BPS, and this review has highlighted the differences in nomenclature, definitions, and recommended diagnostic tests between guidelines. The overall evidence base for the majority of treatments for BPS/IC is of low‐quality, and larger randomised trials are required to more accurately inform guideline recommendations and clinical management of this complex group of patients.
Importance of non‐regional lymph nodes in assigning risk in primary metastatic prostate cancer
Authors: Ali Adnan , Hoyle Alex , Mistry Hitesh , Clarke Noel W.
Published: May 2018

Objective

To determine the prognostic relevance of non‐regional lymph node (NRLN) metastases presenting synchronously with bone metastases in metastatic prostate cancer (mPCa) for guiding treatment decisions based on oligometastatic definitions.

Patients and Methods

Patients diagnosed with mPCa between 2004 and 2013 were identified from the Surveillance, Epidemiology and End Results database and were grouped by metastatic sites into only NRLN, only bone, bone + NRLN and other sites ± bone/NRLN metastases. Multivariate Cox and competing risk regression analyses were performed to compare the risks of all‐cause mortality (ACM) and prostate cancer‐specific mortality (PCSM) associated with bone + NRLN metastases before and after propensity‐score matching to patients with only bone metastases. This was complemented with landmark and supplementary analyses.

Results

Of 17 167 patients with mPCa identified, 63.1% presented with only bone metastases, while bone and NRLN metastases co‐occurred in 8.9% of the cohort. On multivariate analyses, after adjusting for potential confounders (clinical and sociodemographic), patients with bone + NRLN metastases had a significantly higher risk of ACM (hazard ratio [HR] 1.161, 95% confidence interval [CI] 1.084–1.243; P < 0.001) and PCSM (subdistribution HR 1.149, 95% CI 1.067–1.237; P < 0.001) compared with patients with only bone metastases. Landmark analyses limited to survivors of ≥6 and ≥12 months again showed a significantly increased risk of ACM for patients presenting with bone + NRLN metastases compared with patients with only bone metastases. In a subsequent 1:1 propensity‐score‐matched cohort of patients with bone + NRLN metastases and only bone metastases, the bone + NRLN group had higher multivariate‐adjusted hazard rates for ACM (HR 1.202, 95% CI 1.102–1.311; P < 0.001) and PCSM (subdistribution HR 1.146, 95% CI 1.044–1.259; P = 0.004).

Conclusions

Patients with concomitant NRLN and bone metastases have a higher risk of death, NRLN and bone metastases therefore representing a high‐risk feature, when compared with patients with bone metastases alone. The current therapeutic stratification of ‘low‐’ vs ‘high‐volume’ disease does not account for this phenomenon, and patients requiring aggressive combination therapy may not receive maximum therapeutic benefit as a consequence.
Simulation in urology to train non‐technical skills in ward rounds
Authors: Somasundram Khevan , Spence Heather , Colquhoun Alexandra J. , Mcilhenny Craig , Biyani Chandra S. , Jain Sunjay
Published: May 2018

Objective

To report our experience of an exercise designed to train newly appointed urology trainees in non‐technical skills on ward rounds as a part of a simulation ‘boot camp’, through a qualitative analysis of participant feedback on the utility of this method of training.

Patients and Methods

The simulations took place in a high‐fidelity simulated ward bay. Forty‐eight doctors with formal urology training ranging between 2 and 60 months (mean 19.1 ± 11.6 months) took part. Thirty‐one participants were on a formal urology specialty training pathway. The remaining participants were core (pre‐specialty) surgical trainees. The entry requirement was that participants must be junior‐level urologists, ideally at the beginning of specialty training. Participants individually led a simulated ward round, which was devised using actors to play patients and a simulated ‘switchboard’ for telephone conversations. Distractions were introduced deliberately for participants to manage an emergent urology‐related scenario. ‘Freeze‐frames’ were used to ‘pause’ the ward round, whereby observing consultants provided feedback on performance. After the simulated exercises, a whole‐group structured debriefing took place. Non‐Technical Skills for Surgeons (NOTSS) scores were generated for participants by seven consultant urologists. Participants completed a two‐part feedback form. Part one involved nine questions scored on a Likert scale, and part two required free‐text responses.

Results

The mean (±sd) itemized NOTSS scores for situational awareness, decision‐making, communication and teamwork, and leadership were 3.01 (±0.15), 2.95 (±0.16), 3.05 (±0.19), and 2.98 (±0.15), respectively. From the thematic analysis, participants commented positively on the number of scenarios per participant, the use of actors as patients and real staff, and the use of freeze‐frames for immediate feedback. Residents also provided suggestions for distractions to be considered in the future.

Conclusions

This simulated ward round was generally well received by participants, and the obtained feedback provides an insight into how this can be adapted to maximize the benefits for new specialty residents. The mean NOTSS scores indicated that non‐technical skills performances could be improved. This supports our rationale to train non‐technical skills in a safe environment to bolster career transition into positions of greater decision‐making autonomy.
The serotonin (5‐hydroxytryptamine) 5‐HT7 receptor is up‐regulated in Onuf's nucleus in rats with chronic spinal cord injury
Authors: Ni Jianshu , Cao Nailong , Wang Xiaohu , Zhan Changsheng , Si Jiemin , Gu Baojun , Andersson Karl‐Erik
Published: May 2018

Objectives

To examine the effect of intrathecal (i.t.) serotonin (5‐hydroxytryptamine) 5‐HT7 agonist administration on voiding function in the urethane‐anesthetised rat, and the change in 5‐HT7 receptor (5‐HT7R) expression in the lumbosacral cord Onuf's nucleus after spinal cord injury (SCI).

Materials and methods

In all, 32 female Sprague–Dawley (SD) rats were equally divided into a spinally intact (SI) group and SCI group (n = 16 each). At 8 weeks after transection, half of the rats underwent continuous cystometry under urethane anaesthesia, and the 5‐HT7R‐selective agonist LP44 was given (i.t.). The remaining rats were used for pseudorabies (PRV) retrograde tracing, immunofluorescence, and Western Blot.

Results

LP44 administered i.t. had no effect in the SI rats. In SCI rats, LP44 (1–30 μg/kg) induced significant dose‐dependent increases in micturition volume, voiding efficiency, number of high‐frequency oscillations per micturition; and decreases in residual volume, bladder capacity, peak bladder pressure, threshold pressure and non‐voiding contractions. The 5‐HT7R antagonist, SB‐269970 (10 μg/kg), partially reversed LP44‐induced changes. Using PRV retrograde tracing and immunofluorescence, 5‐HT7Rs were found in the L6–S1 spinal cord Onuf's nucleus in both SI and SCI rats, but the expression was significantly greater in the SCI rats. Western blot showed significantly more 5‐HT7Rs in the ventral L6–S1 spinal cord in SCI rats.

Conclusion

A 5‐HT7R agonist, given i.t., improved voiding efficiency in urethane‐anesthetised SCI rats, and the 5‐HT7R was significantly up‐regulated in the lumbosacral cord Onuf's nucleus. If valid for humans, these findings suggest that the 5‐HT7R could be a target for therapeutic interventions.
A narrative approach to helping an adult with a mild learning disability to confront “the gremlin”
Authors: Lewis Vicky , Rose David
Published: May 2018

Accessible summary

Sometimes people with a learning disability find things hard which changes how they think, feel and what they do. The psychology team supports people with feelings, thoughts, relationships and behaviours.

Narrative therapy is a way of helping people to understand things in a different way.

Narrative therapy assumes that people have many skills and are good at lots of things which can help them to reduce the impact of what they find hard.

This is the story of how I helped a woman with a learning disability using narrative therapy. It is important to share this story so that narrative therapy can be used to help other people.

Background

The main assumption of narrative therapy is that people are the “experts” on their own lives. When working with people with a learning disability, it can often be the case that the client’s voice is not the primary voice. This is due to the fact that others “hold” the story for the client. When the story is, therefore, told, it is done so from the perspective of that person. Narrative therapy has been found to provide an opportunity to access the perspective and experience of those whose voice may otherwise be excluded.

Materials and Methods

This paper details a case study which explains how a woman with a mild learning disability was helped to confront overwhelming anxiety which she referred to as “the gremlin.” The client described how “the gremlin” was having an influence over her ability to manage in stressful situations and cope with change. A narrative approach was utilised which focussed on reducing the influence of “the gremlin.”

Results

The client’s evaluation of the therapy using self‐report and scaling measures showed that it had been a success. The client identified times where stories other than the dominant were lived and she became the primary author of preferred stories of her life, reducing the influence of “the gremlin.”

Conclusions

This study described how narrative therapy helped a woman with a learning disability and provides an example for use with other clients in the future.
“Something was wrong”: A narrative inquiry of becoming a father of a child with an intellectual disability in Ireland
Authors: Marsh Lynne , Warren Patricia‐Leahy , Savage Eileen
Published: May 2018

Accessible summary

Ten fathers were asked to tell their story of being told that their child was diagnosed with an intellectual disability.

They said that initially they were shocked, disappointed, in denial and blamed themselves when the diagnosis was certain.

All fathers remembered when they were told and by whom they were told about their child’s diagnosis.

Becoming a father was a reason to be happy.

Background

In recent years, there has been a growth of research on men’s experiences of becoming fathers, most of which relates to a typically developing child without intellectual disabilities. While some studies have specifically explored the experiences of becoming a father of a child with an intellectual disability, there are few studies from an Irish context.

Aim

The aim of this study was to present Irish fathers’ narratives within the context of leading up to the diagnosis and the actual diagnosis of a child’s intellectual disability.

Method

A qualitative narrative inquiry design was used with ten fathers aged 31–48 years through semi‐structured interviews.

Results

This study is part of a larger study focusing on becoming a father of a child with an intellectual disability in Ireland. The findings related to finding out “something was wrong” with the child are presented.

Conclusion

Fathers are emotionally affected by the diagnosis of a child’s intellectual disability. Therefore, healthcare professionals need to be cognisant of the emotional upheaval that such a diagnosis can have on fathers and be sensitive to their needs in supporting them through this process.
Platelets, autotaxin and lysophosphatidic acid signalling: win‐win factors for cancer metastasis
Authors: Leblanc Raphael , Houssin Audrey , Peyruchaud Olivier
Published: May 2018

Platelets play a crucial role in the survival of metastatic cells in the blood circulation. The interaction of tumour cells with platelets leads to the production of plethoric factors among which our review will focus on lysophosphatidic acid (LPA), because platelets are the highest producers of this bioactive lysophospholipid in the organism. LPA promotes platelet aggregation, and blocking platelet function decreases LPA signalling and leads to inhibition of breast cancer cell metastasis. Autotaxin (ATX), a lysophospholipase D responsible for the basal concentration of LPA in blood, was detected in platelet α‐granules. Functionally, active ATX is eventually released following tumour cell‐induced platelet aggregation, thereby promoting metastasis. Megakaryocytes do not express ATX but respond to LPA stimulation. Whether LPA‐primed megakaryocytes contribute to the recently reported negative action of megakaryocytes on cancer metastasis is not yet known. However, an understanding of the ATX/LPA signalling pathways in platelets, cancer cells and megakaryocytes opens up new approaches for fighting cancer metastasis.
MicroRNA‐493 is a prognostic factor in triple‐negative breast cancer
Authors: Yao Ling , Liu Yirong , Cao Zhigang , Li Junjing , Huang Yanni , Hu Xin , Shao Zhiming
Published: May 2018

Breast cancer is one of the most common malignant diseases in women. Triple‐negative breast cancer (TNBC) shows higher aggressiveness and recurrence rates than other subtypes, and there are no effective targets or tailored treatments for TNBC patients. Thus, finding effective prognostic markers for TNBC could help clinicians in their ability to care for their patients. We used tissue microarrays (TMAs) to detect microRNA‐493 (miR‐493) expression in breast cancer samples. A miRCURY LNA detection probe specific for miR‐493 was used in in situ hybridization assays. Staining results were reviewed by two independent pathologists and classified as high or low expression of miR‐493. Kaplan–Meier survival plots and multivariate Cox analysis were carried out to clarify the relationship between miR‐493 and survival. In the Kaplan–Meier analysis, patients with high miR‐493 expression had better disease‐free survival than patients with low miR‐493 expression. After adjusting for common clinicopathological factors in breast cancer, the expression level of miR‐493 was still a significant prognostic factor in breast cancer. Further subtype analysis revealed that miR‐493 expression levels were only significantly prognostic in TNBC patients. These results were validated in the Molecular Taxonomy of Breast Cancer International Consortium database for overall survival. We proved the prognostic role of miR‐493 in TNBC by using one of the largest breast cancer TMAs available and validated it in a large public RNA sequencing database.
Improving metabolic stability with deuterium: The discovery of HWL‐066, a potent and long‐acting free fatty acid receptor 1 agonists
Authors: Liu Chunxia , Li Zheng , Shi Wei , Li Huilan , Wang Nasi , Dai Yuxuan , Liao Chen , Huang Wenlong , Qian Hai
Published: May 2018

The free fatty acid receptor 1 (FFA1) is a potential target due to its function in enhancing of glucose‐stimulated insulin secretion. The FFA1 agonist GW9508 has great potential for the treatment of type 2 diabetes mellitus, but it has been suffering from high plasma clearance probably because the phenylpropanoic acid is vulnerable to β‐oxidation. To identify orally available analog without influence on the unique pharmacological mechanism of GW9508, we tried to interdict the metabolically labile group by incorporating two deuterium atoms at the α‐position of phenylpropionic acid affording compound 4 (HWL‐066). As expected, HWL‐066 revealed a lower clearance (CL = 0.23 L−1 hr−1 kg−1), higher maximum concentration (Cmax = 5907.47 μg/L), and longer half‐life (T1/2 = 3.50 hr), resulting in a 2.8‐fold higher exposure than GW9508. Moreover, the glucose‐lowering effect of HWL‐066 was far better than that of GW9508 and comparable with TAK‐875. Different from glibenclamide, no side‐effect of hypoglycemia was observed in mice after oral administrating HWL‐066 (80 mg/kg).
The Intersection of Race and Gender Among Black American Adolescents
Authors: Seaton Eleanor K. , Tyson Karolyn
Published: May 2018

This study employed an exploratory sequential mixed‐methods design to examine the intersection of race and gender among Black American adolescents, aged 11–19. The quantitative component (n = 344) used survey data to examine gender differences in peer‐perpetrated and adult‐perpetrated racial discrimination experiences, and no gender differences were evident. Qualitative data (n = 42) probed how males and females interpret discrimination experiences given the intersection of race and gender. Although the majority of participants believed that Black males and females have similar experiences, some believed that Black males face more racial discrimination. However, analyses revealed social disadvantages for Black females given that they report inappropriate comments and unwelcome hair touching and limited opportunities for interracial dating compared with Black males.
Allergy in the elderly: A case note review of referrals to an adult allergy clinic
Authors: Gray N. J. , Redshaw E. L. , Isaacs D. , Tarzi M. D. , Smith H. E. , Frew A. J.
Published: May 2018

The UK population is ageing and we can expect more referrals to allergy clinics for this age group. 16% of patients to our clinic are aged >60. Compared to younger patients, 3 times as many referrals were for angioedema. Overall, allergy was excluded in 79% of cases. 15% were diagnosed with previously unrecognised allergies, while allergic disease was confirmed in 6%, enabling optimised management. While the differential diagnosis of allergic conditions is wider in older people, assessment in the allergy clinic is helpful and adds value.
Natural history of Rathke's cleft cysts: A retrospective analysis of a two centres experience
Authors: Sala Elisa , Moore Justin M. , Amorin Alvaro , Carosi Giulia , Martinez Hector , Harsh Griffith R. , Arosio Maura , Mantovani Giovanna , Katznelson Laurence
Published: May 2018

Objective

Rathke's cleft cyst (RCC) is a common sellar lesion which may cause visual impairment, hypopituitarism and headaches from mass effect. The natural history of these lesions is currently unclear. We investigated the natural history of RCCs and compared surgically treated patients with those treated conservatively.

Methods

We performed a retrospective cohort study of patients diagnosed with a RCC between 1996 and 2016 at Stanford University and Ospedale Maggiore Policlinico di Milano.

Results

Patients were divided into 2 cohorts: Group A, 72 subjects who underwent surgical resection of a symptomatic RCC, and Group B, 62 subjects managed conservatively. Compared to Group B, Group A subjects had larger RCCs (79% vs 22% had a largest diameter >10 mm, P < .001) and were more likely (41.5% vs 16%, P < .001) to present with hypopituitarism and diabetes insipidus (DI) (18% vs 1.6%, P = .002). In Group A, after a mean follow‐up of 53.7 months, 12.5% of patients had recurrence and a second surgery. After surgery, 35% of patients recovered pituitary function. Hyperprolactinemia (26.6%) and hypogonadism (66.6%) resolved more commonly that did DI (20.1%). New pituitary deficits appeared in 16.6% of patients after surgery. In Group B, with a mean follow‐up of 41 months, only 6.4% had cyst enlargement, none underwent surgery, and none developed a pituitary deficit.

Conclusion

Our data offer guidance in decision‐making regarding the management of RCC patients and confirm the safety of conservative treatment in asymptomatic patients.
Influence of different drilling preparation on cortical bone: A biomechanical, histological, and micro‐CT study on sheep
Authors: Stocchero Michele , Toia Marco , Jinno Yohei , Cecchinato Francesca , Becktor Jonas P. , Naito Yoshihito , Halldin Anders , Jimbo Ryo
Published: May 2018

Objective

The aim of this study was to investigate the extent of cortical bone remodeling between two different drilling protocols by means of histomorphometric, µ‐CT, and biomechanical analyses.

Material and methods

A total of 48 implants were inserted into the mandible of six sheep following two drilling protocols: Group A (Test, n = 24), undersized preparation; Group B (Control, n = 24), non‐undersized preparation. The animals were euthanatized to obtain 5 and 10 weeks of implantation time. Removal torque (RTQ) was measured on 12 implants of each group and the peri‐implant bone was µ‐CT scanned. Bone volume density (BV/TV) was calculated in pre‐determined cylindrical volumes, up to 1.5 mm from implant surface. Non‐decalcified histology was prepared on the remaining 12 implants from each group, where total bone‐to‐implant contact (totBIC) and newly‐formed BIC (newBIC) was measured. Bone Area Fraction Occupancy (BAFO) was determined in pre‐determined areas up to 1.5 mm from implant surface. Paired sample t test or Wilcoxon signed‐rank test was used to investigate differences between the groups.

Results

Group A presented significantly increased RTQ value at 5 weeks, while no difference was observed at 10 weeks. Group B presented increased BV/TV value at 5 weeks. Both groups showed comparable values for totBIC at both time‐points. However, Group A presented significantly lower newBIC at 5 weeks. Higher BAFO was observed in Group B at 5 weeks.

Conclusions

Implants inserted into undersized sites has an increased biomechanical performance, but provoked major remodeling of the cortical bone during the early healing period compared to non‐undersized preparations. After 10 weeks, no difference was observed.
Seagrass meadows support global fisheries production
Authors: Unsworth Richard K.F. , Nordlund Lina Mtwana , Cullen‐Unsworth Leanne C.
Published: May 2018

The significant role seagrass meadows play in supporting fisheries productivity and food security across the globe is not adequately reflected in the decisions made by authorities with statutory responsibility for their management. We provide a unique global analysis of three data sources to present the case for why seagrass meadows need targeted policy to recognize and protect their role in supporting fisheries production and food security. (1) Seagrass meadows provide valuable nursery habitat to over 1/5th of the world's largest 25 fisheries, including Walleye Pollock, the most landed species on the planet. (2) In complex small‐scale fisheries from around the world (poorly represented in fisheries statistics), we present evidence that many of those in proximity to seagrass are supported to a large degree by these habitats. (3) We reveal how intertidal fishing activity in seagrass is a global phenomenon, often directly supporting human livelihoods. Our study demonstrates that seagrasses should be recognized and managed to maintain and maximize their role in global fisheries production. The chasm that exists between coastal habitat conservation and fisheries management needs to be filled to maximize the chances of seagrass meadows supporting fisheries, so that they can continue to support human wellbeing.
Comparable outcomes in intestinal retransplantation: Single‐center cohort study
Authors: Ekser Burcin , Kubal Chandrashekhar A. , Fridell Jonathan A. , Mangus Richard S.
Published: May 2018

Background

Graft loss in intestinal transplantation (ITx) is close to 25% in the first year and 50% at 5‐year post‐transplantation. Although technically and immunologically challenging, intestinal retransplantation is now the 4th most common indication for ITx.

Methods

The aim of this study was to review and compare the outcomes of intestinal retransplantation with primary ITx, which included isolated ITx, modified multivisceral transplantation (mMVTx), and full MVTx, between 2003 and 2014 at Indiana University.

Results

Of 218 ITx, 18 (8.3%) were retransplantation. Causes of graft loss were rejection(78%), pancreatitis (11%), and severe intestine dismotility (11%). MVTx (16/18, 89%) was the preferred retransplantation option. In 7 (39%) patients, graftectomy was performed between primary and intestinal retransplantation. Median interval between primary ITx and retransplantation was 421 days. Although patient and graft survival rates at 1 year, 3 years, and 5 years were comparable between primary and retransplants, the number of retransplants was limited in the follow‐up after post‐transplant year 3.

Conclusions

We identified that timing of retransplantation, graftectomy prior to retransplant allowing an immunosuppression free state, inclusion of the liver, and preserved renal function are important factors in the consideration of intestinal retransplantation. Immunological aspects remain challenging in the decision making and for short‐ and long‐term outcomes.