bluuebunny/crossref_metadata_2025 huggingface dataset:
Lived Experience of Grieving of Thai Buddhist Husbands Who Had Lost Their Wives From Critical Illness
Authors: Kongsuwan Waraporn , Khaw Tusanee , Chaiweeradet Manee , Locsin Rozzano
Published: March 2019

Purpose

To describe the meanings of the lived experiences of grieving of Thai Buddhist husbands who had lost their wives from critical illnesses.

Design

Hermeneutic phenomenological approach using van Manen's concepts. Seven husbands from southern Thailand who met the inclusion criteria participated in the study.

Methods

Individual in‐depth interviews were conducted and recorded on tape, while the interview data were transcribed and analyzed following van Manen's phenomenological approach. Trustworthiness was established using Lincoln and Guba's criteria.

Findings

Five thematic categories described the meanings of the experiences, which were reflective of the four lived worlds of body, relation, space, and time. The lived world of body was “loss of thoughtful focus and energy,” the lived world of relation was characterized by “surrendering attachment with the deceased” and “attachment to the children,” the lived space reflected “social connection,” and lived time was “healing time.”

Conclusions

The grief experience did not seem to be complicated, and the hoped‐for experience was being healed through surrendering attachment with the deceased while maintaining attachment with children and social connection. The model of grieving may contribute to the knowledge of nursing care processes, specifically in palliative and end‐of‐life care, and other care processes for healthcare professionals.

Clinical Relevance

Hospital administrators can clearly support a bereavement service to provide a continuum of after‐death care for Buddhist males. Nurses and healthcare providers can develop a bereavement care process by valuing the religious principles integrating social interaction for male bereaved husbands.
Well It’s Only Fair: How Perceptions of Manager Discretion in Bonus Allocation Affect Intrinsic Motivation
Authors: Hewett Rebecca , Leroy Hannes
Published: March 2019

Perceptions of manager discretion in incentive allocation are theoretically and practically important to help explain the much‐debated relationship between performance‐related bonuses and intrinsic motivation. We argue, and demonstrate, that perceived managerial discretion is a key moderator to this relationship because of its relevance to procedural fairness. In a first study, we developed a measure for perceived manager discretion and distinguished it from related concepts. In a second experiment, we found that higher bonuses associated with higher levels of perceived manager discretion enhanced procedural fairness but those based on lower discretion did not. In a third field study, we found that actual bonuses implemented by a service organization enhanced intrinsic motivation indirectly through procedural fairness, but only when employees perceived their bonus to be based on higher levels of perceived manager discretion. Conversely, when bonus level was associated with lower perceived manager discretion, it negatively predicted of intrinsic motivation.
Implementing a tailored education programme: renal transplant recipients’ experiences
Authors: Andersen Marit Helen , Wahl Astrid Klopstad , Engebretsen Eivind , Urstad Kristin Hjorthaug
Published: March 2019

Background

Patient‐centred education is a key element in the care of patients undergoing kidney transplantation. We implemented a tailored, evidence‐based education programme for the post‐transplant phase.

Objective

The aim of the study was to explore renal transplant recipients’ experiences of participating in a new, tailored, evidence‐based education programme.

Methods

An explorative qualitative design was chosen to elicit knowledge, insight and understanding of the renal transplant recipients’ perspectives. Twelve renal transplant recipients participated in semi‐structured interviews about eight weeks post‐transplant. The interviews were audiotaped and analysed using thematic data analysis inspired by Kvale and Brinkmann's method for meaning condensation.

Findings

Two main themes emerged: ‘Situated tailoring to the person's everyday life knowledge’, and ‘Tailoring as a standard procedure regardless of the person’.

Conclusion

The findings of the present study indicate that the renal transplant recipients experienced the new education programme to be tailored to individual needs. Our study also revealed that the recipients experienced the health care personnel to take different considerations into account when educating. Viewing knowledge as continuously changing from controlled study contexts into clinical settings, we here demonstrate the need to evaluate new knowledge also after being implemented.
Raloxifene decreases cell viability and migratory potential in prostate cancer cells (LNCaP) with GPR30/GPER1 involvement
Authors: Salata Giovanna Cassone , Pinho Cristiane Figueiredo , de Freitas André T A G , Aquino Ariana Musa , Justulin Luis Antonio , Mendes Leonardo Oliveira , Gonçalves Bianca F , Delella Flávia Karina , Scarano Wellerson Rodrigo
Published: March 2019

Objectives

This study evaluated raloxifene (ral) effects on LNCaP prostate tumour cells modulating the activity of GPER1/GPR30 receptors.

Methods

LNCaP cells were submitted for 40/120 min and 12 h to the following treatments: C: RPMI + DMSO; R: RPMI + Ral; G: RPMI + Ral + G15 (GPER1 antagonist). Trypan blue staining measured cell viability. Migratory potential (12 h) was measured by transwell migration test in translucent inserts, which were then stained with DAPI and analysed under a fluorescence microscope for quantification. Cells from 40- and 120-min treatments were subjected to protein extraction to the study of AKT, pAKT, ERK, pERK, ERβ and SIRT1.

Key findings

There is a reduction in cellular viability in R compared to C at all evaluated times, and an increased cell viability in G when compared to R; cell viability was similar in C and G in all times studied. The migration assay demonstrated a significant decrease in migration potential of tumour cells in R compared to C and G. Ral treatment reduced pERK expression and increased pAKT in the treated groups after 40 min, pointing out to an antiproliferative and apoptotic effect in the GPER1-controlled rapid-effect pathways.

Conclusions

Raloxifene was able to modulate GPER1 in LNCaP prostate tumour cells, decreasing cell viability and their migratory potential.
Crude protein in low‐fish meal diets for juvenile Litopenaeus vannamei can be reduced through a well‐balanced supplementation of essential amino acids
Authors: Nunes Alberto J. P. , Sabry‐Neto Hassan , Masagounder Karthik
Published: March 2019

The use of supplemental essential amino acids (EAAs) has been shown to provide an opportunity to minimize excess levels of crude protein (CP) in animal feeds. The present study investigated the effect of reducing the amount of CP in low‐fish meal diets (5%) for juvenile Litopenaeus vannamei. Four sets of diets were prepared containing (% on a fed basis, mean ± SD) 31.24 ± 0.71, 33.70 ± 0.41, 36.90 ± 0.44, and 39.63 ± 0.14% CP, with each protein level containing a total dietary methionine (Met) (Met + Cys) level of 0.56 ± 0.02 (1.07 ± 0.23), 0.71 ± 0.01 (1.22 ± 0.20), 0.88 ± 0.02 (1.38 ± 0.22), or 1.04 ± 0.02% (1.55 ± 0.18%). Shrimp of 1.00 ± 0.08 g were stocked in 84 outdoor tanks of 1 m3 at a rate of 100 shrimp/m2 and raised for 75 days. Final survival ranged from 83 to 97% and was unaffected by Met content. Both survival and yield were significantly depressed when shrimp were fed the 31% CP diet. Shrimp grew at a weekly rate of between 0.79 and 0.97 g, achieving a final body weight (BW) in excess of 10.8 g. There was a significant interaction between CP and Met over BW. Shrimp fed 0.56% Met achieved the lowest BW at harvest. Increasing CP beyond 34% did not enhance BW. With a dietary Met content of 0.71%, the highest BW was achieved with 34% CP compared to other levels. There was a significant improvement in Feed Conversion Ratio (FCR) when CP was raised from 31 to 34%. Similarly, dietary Met levels above 0.71% resulted in a significantly better FCR compared to 0.56%. Our study has shown that, if dietary Met (Met + Cys) meets a minimum of 0.71% (1.22%), levels of CP could be reduced from 40 to 34% without adverse effects on shrimp performance.
Don’t forget to ask how mum and dad are doing
Authors: Romeo Stefano
Published: March 2019

See Article on Page 740
Growing muscle against cirrhosis: In the quest for models to revealing mechanisms
Authors: Asensio Iris , Vaquero Javier
Published: March 2019

See Article on Page 676
Fibroblast growth factor 21 is independently associated with severe hepatic steatosis in non‐obese HIV‐infected patients
Authors: Praktiknjo Michael , Djayadi Natalie , Mohr Raphael , Schierwagen Robert , Bischoff Jenny , Dold Leona , Pohlmann Alessandra , Schwarze‐Zander Carolynne , Wasmuth Jan‐Christian , Boesecke Christoph , Rockstroh Jürgen K. , Trebicka Jonel
Published: March 2019

Background

Severe hepatic steatosis shows a high prevalence and contributes to morbidity and mortality in human immunodeficiency virus (HIV) infected patients. Known risk factors include obesity, dyslipidaemia and features of metabolic syndrome. Fibroblast growth factor 21 (FGF‐21) is involved with hepatic glucose and lipid metabolism. This study aimed to evaluate FGF‐21 as a biomarker for severe hepatic steatosis in non‐obese HIV‐infected patients.

Methods

This is a prospective, cross‐sectional, monocentric study including HIV‐infected out‐patients. Hepatic steatosis was measured via controlled attenuation parameter (CAP) using FibroScan 502 touch (ECHOSENS, France). Severe hepatic steatosis was defined at CAP ≥ 253 dB/m. Peripheral blood samples were collected and plasma was analysed for FGF‐21. Demographic and clinical characteristics were collected from patient's health records.

Results

In total, 73 non‐obese HIV‐monoinfected patients were included in this study. Prevalence of severe hepatic steatosis was 41%. Patients with severe hepatic steatosis showed significantly higher levels of FGF‐21. Univariate analysis revealed FGF‐21, BMI, hyperlipidaemia, ALT levels and arterial hypertension as significant, while multivariate analysis showed only FGF‐21, arterial hypertension and ALT levels as significant independent risk factors for severe hepatic steatosis.

Conclusion

This study presents FGF‐21 as an independent and stronger predictor of severe hepatic steatosis than blood lipids in HIV‐infected patients. Moreover, arterial hypertension and ALT levels predict severe steatosis even in non‐obese HIV‐monoinfected patients. Furthermore, this study supports existing metabolic risk factors and expands them to non‐obese HIV‐infected patients.
Fostering novice students' diagnostic ability: the value of guiding deliberate reflection
Authors: Mamede Sílvia , Figueiredo‐Soares Taciana , Elói Santos Silvana M , de Faria Rosa M D , Schmidt Henk G , van Gog Tamara
Published: March 2019

Background

Deliberate reflection when practising the diagnosis of clinical cases has been shown to develop medical students' diagnostic competence. Adding guidance by cueing reflection or providing modelling of reflection increased the benefits of reflection for advanced (Years 5–6) students. The present study investigated whether we could replicate and extend these findings by comparing the effects of free, cued and modelled reflection on novice students' diagnostic competence.

Methods

A total of 80 third‐year medical students participated in a two‐phase experiment. In the learning phase, students diagnosed nine clinical cases under one of three conditions: free reflection; cued reflection, and modelled reflection. Two weeks later, all students diagnosed four new examples of the diseases studied in the learning phase and four cases of non‐studied related diseases (‘adjacent diseases’). The main outcome measurements were diagnostic accuracy scores (range 0–1) on studied and adjacent diseases.

Results

For studied diseases, there was a significant effect of experimental condition on diagnostic accuracy (p < 0.02), with the cued‐reflection group (mean = 0.58, standard deviation [SD] = 0.23) performing significantly better than the free‐reflection group (mean = 0.41, SD = 0.20; p < 0.02). The cued‐reflection and modelled‐reflection groups (mean = 0.54, SD = 0.22) did not differ in diagnostic accuracy (p > 0.05), nor did the modelled‐reflection group perform better than the free‐reflection group (p > 0.05). For adjacent diseases, the three groups scored extremely low, without significant differences in performance (p > 0.05). Cued reflection and free reflection were rated as requiring similar effort (p > 0.05) and both were more demanding than studying examples of reflection (both p < 0.001) in the learning phase.

Conclusions

Simply cueing novice students' reflection to focus it on relevant diseases was sufficient to increase diagnostic performance relative to reflection without any guidance. Cued reflection and studying examples of reflection appear to be equally useful approaches for teaching clinical diagnosis to novice students. Students found studying examples of reflection required less effort but cued reflection will certainly demand much less investment from teachers.
Macro to micro: microwave remote sensing of plant water content for physiology and ecology
Authors: Konings Alexandra G. , Rao Krishna , Steele‐Dunne Susan C.
Published: March 2019

Although primarily valued for their suitability for oceanographic applications and soil moisture estimation, microwave remote sensing observations are also sensitive to plant water content (Mw). Since Mw depends on both plant water status and biomass, these observations have the potential to be useful for a range of plant drought response studies. In this paper, we introduce the principles behind microwave remote sensing observations to illustrate how they are sensitive to plant water content and discuss the relationship between landscape‐scale Mw and common stand‐scale metrics, including plant‐scale relative water content, live fuel moisture content and leaf water potential. Lastly, we discuss how various sensor types can be leveraged for specific applications depending on the spatio‐temporal resolution needed.
Pornography, preference for porn‐like sex, masturbation, and men's sexual and relationship satisfaction
Authors: Miller Dan J. , McBain Kerry A. , Li Wendy W. , Raggatt Peter T. F.
Published: March 2019

Pornography use, preference for “porn‐like” sex, masturbation, and sexual and relationship satisfaction were assessed among two samples of men (NStudy 1 = 326, NStudy 2 = 335). Frequent pornography use was associated with sexual dissatisfaction, greater preference for porn‐like sex, and more frequent masturbation in both studies. Pornography use was associated with relationship dissatisfaction in Study 2 only. The data did not support the notion that pornography negatively impacts sexual or relationship satisfaction via preference for porn‐like sex. In fact, it may bolster sexual satisfaction by promoting sexual variety. The data were consistent with a model in which pornography negatively, indirectly affects sexual and relationship satisfaction via masturbation frequency. Pornography use may have multiple opposing influences on sexual satisfaction.
The race between host and sea lice in the Chilean salmon farming: a genomic approach
Authors: Gallardo‐Escárate Cristian , Arriagada Gabriel , Carrera Crisleri , Gonçalves Ana Teresa , Nuñez‐Acuña Gustavo , Valenzuela‐Miranda Diego , Valenzuela‐Muñoz Valentina
Published: March 2019

Sea lice are a group of ectoparasite copepods negatively affecting fish health in the salmon farming industry worldwide. Due to their biology, including several stages of development with different sensitivities to chemotherapeutants and their complex host–parasite interactions, the control of sea lice represents one of the major obstacles for sustainable aquaculture. Interdisciplinary approaches are required to avoid the environmental impacts of antiparasites commercially used during the fish production cycle and the increasing emergence of drug resistance in lice populations. Herein, control methods based on genomic analyses will allow for the development of novel tools such as vaccines, immune‐modulators, in‐feed masking compounds and non‐pharmacological therapies. This review highlights the genomic knowledge on the race between hosts and sea lice, with emphasis on Salmo salar and Oncorhynchus kisutch as host fish species and Caligus rogercresseyi as the main threat affecting the Chilean salmon industry.
A guinea for a guinea pig: a manuscript satire on England’s first animal–human blood transfusion
Authors: Bičak Ivana
Published: March 2019

This article examines a manuscript satire of a famous case of seventeenth‐century blood transfusion in England between a man and a sheep. The poem, transcribed at the end of the article, tells the story of Arthur Coga, a clergyman and alcoholic who was offered money in 1667 to take part in a dangerous experiment by Royal Society physicians. The verses tackle crucial ethical points of medical experimentation in the period and mock the novel scientific procedures of the newly established Royal Society. The problems of scientific exploitation, complicity, and informed consent are dealt with in a poetic fashion, through the use of realised metaphors, local legends, and classical mythology. The article argues that the poem acts as a site of transformations, both rhetorical and literal. The practice of transfusion transforms poetry itself, and influences the choice of poetic devices. At the same time, the poem's humour serves as a powerful weapon in the incrimination of the new experimental procedure.
D'Alembert‐type solution of the Cauchy problem for the Boussinesq‐Klein‐Gordon equation
Authors: Khusnutdinova Karima R. , Tranter Matthew R.
Published: March 2019

In this paper, we construct a weakly‐nonlinear d'Alembert‐type solution of the Cauchy problem for the Boussinesq‐Klein‐Gordon (BKG) equation. Similarly to our earlier work based on the use of spatial Fourier series, we consider the problem in the class of periodic functions on an interval of finite length (including the case of localized solutions on a large interval), and work with the nonlinear partial differential equation with variable coefficients describing the deviation from the oscillating mean value. Unlike our earlier paper, here we develop a novel multiple‐scales procedure involving fast characteristic variables and two slow time scales and averaging with respect to the spatial variable at a constant value of one or another characteristic variable, which allows us to construct an explicit and compact d'Alembert‐type solution of the nonlinear problem in terms of solutions of two Ostrovsky equations emerging at the leading order and describing the right‐ and left‐propagating waves. Validity of the constructed solution in the case when only the first initial condition for the BKG equation may have nonzero mean value follows from our earlier results, and is illustrated numerically for a number of instructive examples, both for periodic solutions on a finite interval, and localized solutions on a large interval. We also outline an extension of the procedure to the general case, when both initial conditions may have nonzero mean values. Importantly, in all cases, the initial conditions for the leading‐order Ostrovsky equations by construction have zero mean, while initial conditions for the BKG equation may have nonzero mean values.
Climatic and sea‐level control of Jurassic (Pliensbachian) clay mineral sedimentation in the Cardigan Bay Basin, Llanbedr (Mochras Farm) borehole, Wales
Authors: Deconinck Jean‐François , Hesselbo Stephen P. , Pellenard Pierre
Published: March 2019

Early Jurassic climate is characterized by alternating cold and warm periods highlighted by studies based notably on oxygen isotopes measured on belemnite guards and other marine invertebrate shells. These climatic changes include changes in the hydrological cycle, and consequently weathering and runoff conditions. In order to clarify the erosion and weathering conditions during the Pliensbachian, this study determined the mineralogical composition of the clay fraction of 132 samples taken from the entire stage drilled in the Llanbedr (Mochras Farm) borehole (Cardigan Bay Basin). The clay mineral assemblages are composed of various proportions of chlorite, illite, illite/smectite mixed‐layers (R1 I–S), smectite and kaolinite, with possibly occasional traces of berthierine. The occurrence of abundant smectite indicates that the maximum burial temperature never exceeded 70°C. Consequently, clay minerals are considered mainly detrital, and their fluctuations likely reflect environmental changes. The variations in the proportions of smectite and kaolinite are opposite to each other. Kaolinite is particularly abundant at the base of the jamesoni Zone, in part coinciding with the δ13C negative excursion corresponding to the Sinemurian/Pliensbachian Boundary Event, and through the davoei Zone, whilst smectite is abundant in the upper part of jamesoni and base of ibex zones and through the subnodosus/gibbosus subzones of the margaritatus Zone. The kaolinite‐rich intervals reflect an intensification of hydrolysis and an acceleration of the hydrological cycle, while the smectite‐rich intervals indicate a more arid climate. The spinatum Zone is characterized by a distinct clay assemblage with abundant primary minerals, R1 I–S, kaolinite reworked from previously deposited sediments or from Palaeozoic rocks, and probably berthierine originating from contemporaneous ironstone‐generating environments of shallower waters. This mineralogical change by the end of the Pliensbachian likely reflects a transition from a dominant chemical weathering to a deeper physical erosion of the continent, probably related to a significant sea‐level fall consistent with a glacio‐eustatic origin.
Leaching of dissolved organic carbon and nitrogen under cotton farming systems in a Vertisol
Authors: Nachimuthu Gunasekhar , Watkins Mark D. , Hulugalle Nilantha R. , Weaver Timothy B. , Finlay Lloyd A. , McCorkell Bruce E.
Published: March 2019

Leaching with deep drainage is one of the loss pathways of carbon (C) and nitrogen (N) in cropping fields. However, field studies in irrigated row cropping systems are sparse. A 3‐year investigation on C and N leaching associated with deep drainage was overlaid on a long‐term experiment on tillage practices and crop rotations in Australia. The treatments included cotton (Gossypium hirsutum L.) monoculture and cotton–wheat (Triticum aestivum L.) or maize (Zea maize L.) rotations with maximum or minimum tillage. The deep drainage C and N concentrations at 0.6 and 1.2 m depth were measured after furrow irrigation with ceramic cup samplers during the 2014–15, 2015–16 and 2016–17 cotton seasons. Pre‐planting dissolved organic carbon (DOC) concentration in soil at 0.6–1.2 m depth during 2016–17 was 64 mg kg−1 for maximum tilled cotton monoculture, 36 mg kg−1 for minimum tilled cotton monoculture and 39 mg kg−1 for cotton–wheat, and in maize and cotton subplots 51 and 41 mg kg−1, respectively. Post‐harvest DOC values in soil were similar in all treatments (average of 32 mg DOC kg−1). Total organic carbon (TOC) losses in deep drainage were equal to 2%–30% of TOC gained in irrigation water. Oxidized N losses in deep drainage ranged from 0.7% to 12% of applied N (260 kg ha−1). NOx‐N concentrations in leachate under maize systems (20 mg L−1) were up to 73% lower than those in cotton systems (75 mg L−1). Maize sown in rotation with cotton can improve cotton yield, reduce N leaching and improve N use efficiency of subsequent cotton.
An Examination of the Pre-competition and Post-competition State Anxiety Levels of Russian Women’s National Volleyball Team Athletes
Authors: Şekeroğlu Mustafa Önder
Published: March 2019

This study of 14 Russian women’s national volleyball team athletes aimed to determine their pre-competition and post-competition state anxiety levels according to some variables. This descriptive study used the Competition State Anxiety Inventory-2 (CSAI-2) developed by Martens, Burton, Vealey, Bump and Smith (1990). This inventory has 9 items in 3 sub-factors: cognitive anxiety, somatic anxiety and self-confidence.A comparison of the pre-competition and post-competition anxiety levels found no statistically significant differences in cognitive anxiety (p>0.05), somatic anxiety (p>0.05) and self-confidence (p>0.05). The highest pre-competition somatic anxiety score fell after the competition, while cognitive anxiety and self-confidence increased after the competition when it was low. There were no statistically significant differences in the athletes’ pre-competition and post-competition anxiety levels by age or income. Considering that success does not occur without a certain level of anxiety, coaches should consider the impact of psychological factors in technical and tactical training.
El control de la vida personal, social y económica: desarrollo y estudio exploratorio de una escala de medida
Authors: Morante Benadero Maria Eugenia , Costa Cabanillas Miguel , Esteban y Peña María Mercedes
Published: March 2019

En este trabajo se presenta un estudio exploratorio sobre las características psicométricas de un instrumento sobre el control de de la vida personal, analizando su estructura factorial mediante un análisis exploratorio y confirmatorio de sus dimensiones. El tamaño del estudio final fue de 8.504 entrevistas y el criterio básico de estratificación fue el distrito municipal en 21 estratos. Los resultados encontrados señalan que los ítems en cada una de las dimensiones y sus pesos factoriales son aceptables y se relacionan con enunciados genéricos sobre la atribución de control. A su vez, los índices de bondad de ajuste encontrados de cada uno de los modelos propuestos, arrojan información interesante sobre las posibilidades que este cuestionario ofrece.
The Present Challenge of Transonic Compressor Blade Design
Authors: Hergt Alexander , Klinner J. , Wellner J. , Willert C. , Grund S. , Steinert W. , Beversdorff M.
Published: March 2019

The flow through a transonic compressor cascade shows a very complex structure due to the occurring shock waves. In addition, the interaction of these shock waves with the blade boundary layer inherently leads to a very unsteady flow behavior. The aim of the current investigation is to quantify this behavior and its influence on the cascade performance as well as to describe the occurring transonic flow phenomena in detail. Therefore, an extensive experimental investigation of the flow in a transonic compressor cascade has been conducted within the transonic cascade wind tunnel of DLR Institute of Propulsion Technology at Cologne. In this process, the flow phenomena were thoroughly examined for an inflow Mach number of 1.21. The experiments investigate both the laminar and the turbulent shock wave boundary layer interaction within the blade passage and the resulting unsteady behavior. The experiments show a fluctuation range of the passage shock wave of about 10% chord for both cases, which is directly linked with a change of the inflow angle and of the operating point of the cascade. Thereafter, Reynolds-averaged Navier–Stokes (RANS) simulations have been performed aiming at the verification of the reproducibility of the experimentally examined flow behavior. Here, it is observed that the dominant flow effects are not reproduced by a steady numerical simulation. Therefore, a further unsteady simulation has been carried out to capture the unsteady flow behavior. The results from this simulation show that the fluctuation of the passage shock wave can be reproduced but not in the correct magnitude. This leads to a remaining weak point within the design process of transonic compressor blades because the working range will be overpredicted. The resulting conclusion of this study is that the use of scale-resolving methods such as LES or the application of DNS is necessary to correctly predict unsteadiness of the transonic cascade flow and its impact on the cascade performance.
Researchers probe jail before trial
Authors: Matacic Catherine
Published: March 2019

Efforts to reform U.S. detention policies highlight a shortage of robust studies.
T cell stemness and dysfunction in tumors are triggered by a common mechanism
Authors: Vodnala Suman Kumar , Eil Robert , Kishton Rigel J. , Sukumar Madhusudhanan , Yamamoto Tori N. , Ha Ngoc-Han , Lee Ping-Hsien , Shin MinHwa , Patel Shashank J. , Yu Zhiya , Palmer Douglas C. , Kruhlak Michael J. , Liu Xiaojing , Locasale Jason W. , Huang Jing , Roychoudhuri Rahul , Finkel Toren , Klebanoff Christopher A. , Restifo Nicholas P.
Published: March 2019

Stemness against adversity

T lymphocytes are powerful immune cells that can destroy tumors, but cancers have developed tricks to evade killing. Vodnala
et al.
found that potassium ions in the tumor microenvironment serve a dual role of influencing T cell effector function and stemness (see the Perspective by Baixauli Celda
et al.
). Increased potassium impairs T cell metabolism and nutrient uptake, resulting in a starvation state known as autophagy. The increased potassium can also preserve T cells in a stem-like state where they retain the capacity to divide. These seemingly divergent processes are linked to the cellular distribution of acetyl–coenzyme A, which, when manipulated, can restore the ability of human T cells to eliminate tumors in mice.

Science
, this issue p.
eaau0135
; see also p.
1395
Amphibian fungal panzootic causes catastrophic and ongoing loss of biodiversity
Authors: Scheele Ben C. , Pasmans Frank , Skerratt Lee F. , Berger Lee , Martel An , Beukema Wouter , Acevedo Aldemar A. , Burrowes Patricia A. , Carvalho Tamilie , Catenazzi Alessandro , De la Riva Ignacio , Fisher Matthew C. , Flechas Sandra V. , Foster Claire N. , Frías-Álvarez Patricia , Garner Trenton W. J. , Gratwicke Brian , Guayasamin Juan M. , Hirschfeld Mareike , Kolby Jonathan E. , Kosch Tiffany A. , La Marca Enrique , Lindenmayer David B. , Lips Karen R. , Longo Ana V. , Maneyro Raúl , McDonald Cait A. , Mendelson Joseph , Palacios-Rodriguez Pablo , Parra-Olea Gabriela , Richards-Zawacki Corinne L. , Rödel Mark-Oliver , Rovito Sean M. , Soto-Azat Claudio , Toledo Luís Felipe , Voyles Jamie , Weldon Ché , Whitfield Steven M. , Wilkinson Mark , Zamudio Kelly R. , Canessa Stefano
Published: March 2019

The demise of amphibians?

Rapid spread of disease is a hazard in our interconnected world. The chytrid fungus
Batrachochytrium dendrobatidis
was identified in amphibian populations about 20 years ago and has caused death and species extinction at a global scale. Scheele
et al.
found that the fungus has caused declines in amphibian populations everywhere except at its origin in Asia (see the Perspective by Greenberg and Palen). A majority of species and populations are still experiencing decline, but there is evidence of limited recovery in some species. The analysis also suggests some conditions that predict resilience.

Science
, this issue p.
1459
; see also p.
1386
Remembered reward locations restructure entorhinal spatial maps
Authors: Butler William N. , Hardcastle Kiah , Giocomo Lisa M.
Published: March 2019

Reward and the map in the brain

Recent findings suggest a more complex role of grid cells in the brain than simply coding for space. The grid map in the entorhinal cortex, which is responsible for encoding spatial information, is not as rigid as originally thought and can be distorted by environmental modifications (see the Perspective by Quian Quiroga). Butler
et al.
compared grid cell coding during a free-foraging task and a spatial memory task in rats. They discovered that entorhinal spatial maps restructure to incorporate the location of a learned reward. Boccara
et al.
tested the influence of behaviorally relevant information on the cognitive map that emerges from grid cell firing in the rat medial entorhinal cortex. They found that grid cells participate in neural coding of the goal locality, not the whole environment.

Science
, this issue p.
1447
, p.
1443
; see also p.
1388
Identification of a Novel Plasmid Carrying
mcr-4.3
in an
Acinetobacter baumannii
Strain in China
Authors: Ma Furong , Shen Cong , Zheng Xiaobin , Liu Yan , Chen Hongtao , Zhong Lanlan , Liang Yingjian , Liao Kang , Xia Yong , Tian Guo-Bao , Yang Yongqiang
Published: March 2019

Here, we identified
mcr-4.3
in
Acinetobacter baumannii
, which had not been previously observed to carry an
mcr
gene. The
mcr-4.3
-harboring
A. baumannii
strain AB18PR065 was isolated from pig feces from a slaughterhouse in Guangdong Province of China.
Treatment-Shortening Effect of a Novel Regimen Combining Clofazimine and High-Dose Rifapentine in Pathologically Distinct Mouse Models of Tuberculosis
Authors: Saini Vikram , Ammerman Nicole C. , Chang Yong Seok , Tasneen Rokeya , Chaisson Richard E. , Jain Sanjay , Nuermberger Eric , Grosset Jacques H.
Published: March 2019

Clofazimine and high-dose rifapentine have each separately been associated with treatment-shortening activity when incorporated into tuberculosis (TB) treatment regimens. We hypothesized that both modifications, i.e., the addition of clofazimine and the replacement of rifampin with high-dose rifapentine, in the first-line regimen for drug-susceptible TB would significantly shorten the duration of treatment necessary for cure.
Glucosylceramidase Maintains Influenza Virus Infection by Regulating Endocytosis
Authors: Drews Kelly , Calgi Michael P. , Harrison William Casey , Drews Camille M. , Costa-Pinheiro Pedro , Shaw Jeremy Joseph Porter , Jobe Kendra A. , Nelson Elizabeth A. , Han John D. , Fox Todd , White Judith M. , Kester Mark
Published: March 2019

Influenza virus is the pathogen responsible for the second largest pandemic in human history. A better understanding of how influenza virus enters host cells may lead to the development of more-efficacious therapies against emerging strains of the virus. Here we show that the glycosphingolipid metabolizing enzyme glucosylceramidase is required for optimal influenza virus trafficking to late endosomes and for consequent fusion, entry, and infection. We also provide evidence that promotion of influenza virus entry by glucosylceramidase extends to other endosome-entering viruses and is due to a general requirement for this enzyme, and hence for optimal levels of glucosylceramide, for efficient trafficking of endogenous cargos, such as the epidermal growth factor (EGF) receptor, along the endocytic pathway. This work therefore has implications for the basic process of endocytosis as well as for pathogenic processes, including virus entry and Gaucher disease.
Corneal biomechanics and biomechanically corrected intraocular pressure in primary open-angle glaucoma, ocular hypertension and controls
Authors: Vinciguerra Riccardo , Rehman Salwah , Vallabh Neeru A , Batterbury Mark , Czanner Gabriela , Choudhary Anshoo , Cheeseman Robert , Elsheikh Ahmed , Willoughby Colin E
Published: March 2019

Aims

To compare the biomechanically corrected intraocular pressure (IOP) estimate (bIOP) provided by the Corvis-ST with Goldmann applanation tonometry (GAT-IOP) in patients with high-tension and normal-tension primary open-angle glaucoma (POAG; HTG and NTG), ocular hypertension (OHT) and controls. Moreover, we compared dynamic corneal response parameters (DCRs) of the Corvis-ST in POAG, OHT and controls, evaluated the correlation between global visual field parameters mean deviation and pattern SD (MD and PSD) and DCRs in the POAG group.

Methods

156 eyes of 156 patients were included in this prospective, single-centre, observational study, namely 41 HTG and 33 NTG, 45 OHT cases and 37 controls. Central corneal thickness (CCT), GAT-IOP and bIOP were measured, GAT-IOP was also adjusted for CCT (GATAdj). DCRs provided by Corvis-ST were evaluated, MD and PSD were recorded by 24–2 full-threshold visual field. To evaluate the difference in DCRs between OHT, HTG and NTG, a general linear model was used with sex, medications and group as fixed factors and bIOP and age as covariates.

Results

There was a significant difference between GAT-IOP, GATAdj and bIOP in NTG and HTG, OHT and controls. NTG corneas were significantly softer and more deformable compared with controls, OHT and HTG as demonstrated by significantly lower values of stiffness parameters A1 and highest concavity and higher values of inverse concave radius (all p<0.05). There was a significant correlation (p<0.05) between MD, PSD and many DCRs with POAG patients with softer or more compliant corneas more likely to show visual field defects.

Conclusions

Corneal biomechanics might be a significant confounding factor for IOP measurement that should be considered in clinical decision-making. The abnormality of corneal biomechanics in NTG and the significant correlation with visual field parameters might suggest a new risk factor for the development or progression of NTG.
Serine proteases as luminal mediators of intestinal barrier dysfunction and symptom severity in IBS
Authors: Edogawa Shoko , Edwinson Adam L , Peters Stephanie A , Chikkamenahalli Lakshmikanth L , Sundt Wendy , Graves Sara , Gurunathan Sakteesh V , Breen-Lyles Margaret , Johnson Stephen , Dyer Roy , Graham Rondell , Chen Jun , Kashyap Purna , Farrugia Gianrico , Grover Madhusudan
Published: March 2019

Objective

The intestinal lumen contains several proteases. Our aim was to determine the role of faecal proteases in mediating barrier dysfunction and symptoms in IBS.

Design

39 patients with IBS and 25 healthy volunteers completed questionnaires, assessments of in vivo permeability, ex vivo colonic barrier function in Ussing chambers, tight junction (TJ) proteins, ultrastructural morphology and 16 s sequencing of faecal microbiota rRNA. A casein-based assay was used to measure proteolytic activity (PA) in faecal supernatants (FSNs). Colonic barrier function was determined in mice (ex-germ free) humanised with microbial communities associated with different human PA states.

Results

Patients with IBS had higher faecal PA than healthy volunteers. 8/20 postinfection IBS (PI-IBS) and 3/19 constipation- predominant IBS had high PA (>95th percentile). High-PA patients had more and looser bowel movements, greater symptom severity and higher in vivo and ex vivo colonic permeability. High-PA FSNs increased paracellular permeability, decreased occludin and increased phosphorylated myosin light chain (pMLC) expression. Serine but not cysteine protease inhibitor significantly blocked high-PA FSN effects on barrier. The effects on barrier were diminished by pharmacological or siRNA inhibition of protease activated receptor-2 (PAR-2). Patients with high-PA IBS had lower occludin expression, wider TJs on biopsies and reduced microbial diversity than patients with low PA. Mice humanised with high-PA IBS microbiota had greater in vivo permeability than those with low-PA microbiota.

Conclusion

A subset of patients with IBS, especially in PI-IBS, has substantially high faecal PA, greater symptoms, impaired barrier and reduced microbial diversity. Commensal microbiota affects luminal PA that can influence host barrier function.
Long-term mortality and cardiovascular burden for adult survivors of coarctation of the aorta
Authors: Lee Melissa G Y , Babu-Narayan Sonya V , Kempny Aleksander , Uebing Anselm , Montanaro Claudia , Shore Darryl F , d’Udekem Yves , Gatzoulis Michael A
Published: March 2019

Objective

To examine the contemporary long-term outcome after coarctation repair.

Methods

This is a retrospective cohort study of 834 patients aged ≥16 years who underwent coarctation repair under single-centre follow-up. Repair was performed at a median age of 3 years (lower-upper quartile: 1 month to 15 years) by surgery in 83% (690/834) and angioplasty/stenting in 17% (144/834). Survival was compared with an age- and gender matched normal population. Other outcomes included arch reintervention, aortic valve intervention, ascending aortic intervention, and residual/re-coarctation and resting hypertension at latest follow-up.

Results

After a median follow-up of 27 years (lower-upper quartile: 18–36), there were 38 late deaths (5%, 38/834). Overall survival was 99%, 88% and 65% at 30, 50 and 70 years of age, respectively, significantly reduced compared with a matched normal population (standardised mortality ratio: 3.20, log-rank: p<0.001). Thirty per cent (246/834) required ≥1 arch reintervention, 13% (111/834) an aortic valve intervention and 5% (43/834) an ascending aortic intervention. Freedom from aortic valve and ascending aortic intervention was 83% and 92% at 50 years and 53% and 81% at 70 years of age, respectively. Residual/re-coarctation (gradient ≥25 mm Hg or repair site/diaphragm ratio ≤70%) at latest follow-up was present in 60% (282/474) and resting hypertension in 57% (379/661).

Conclusions

Long-term survival in contemporary adult survivors of coarctation repair is significantly lower than a matched normal population with accelerated decline after the third decade. Nearly 60% of patients eventually develop hypertension, whereas approximately 50% require further invasive cardiovascular treatment by 50 years of age. Our risk-stratifying data may enable personalised follow-up strategies for this common congenital heart condition.
Red cell adenylate kinase deficiency in India: identification of two novel missense mutations (c.71A>G and c.413G>A)
Authors: Dongerdiye Rashmi , Kamat Pranoti , Jain Punit , Warang Prashant , Devendra Rati , Wasekar Nilesh , Sharma Ratna , Mhaskar Ketaki , Madkaikar Manisha R , Manglani Mamta V , Kedar Prabhakar S
Published: March 2019

Adenylate kinase (AK) deficiency is a rare erythroenzymopathy associated with hereditary nonspherocytic haemolytic anaemia along with mental/psychomotor retardation in few cases. Diagnosis of AK deficiency depends on the decreased level of enzyme activity in red cell and identification of a mutation in theAK1gene. Until, only eight mutations causing AK deficiency have been reported in the literature. We are reporting two novel missense mutation (c.71A > G and c.413G > A) detected in theAK1gene by next-generation sequencing (NGS) in a 6-year-old male child from India. Red cell AK enzyme activity was found to be 30% normal. We have screened a total of 32 family members of the patient and showed reduced red cell enzyme activity and confirm mutations by Sanger’s sequencing. On the basis of Sanger sequencing, we suggest that the proband has inherited a mutation inAK1gene exon 4 c.71A > G (p.Gln24Arg) from paternal family and exon 6 c.413G > A (p.Arg138His) from maternal family. Bioinformatics tools, such as SIFT, Polymorphism Phenotyping v.2, Mutation Taster, MutPred, also confirmed the deleterious effect of both the mutations. Molecular modelling suggests that the structural changes induced by p.Gln24Arg and p.Arg138His are pathogenic variants having a direct impact on the structural arrangement of the region close to the active site of the enzyme. In conclusion, NGS will be the best solution for diagnosis of very rare disorders leading to better management of the disease. This is the first report of the red cell AK deficiency from the Indian population.
Socioeconomic and gender inequalities in neonatal, postneonatal and child mortality in India: a repeated cross-sectional study, 2005–2016
Authors: Karlsson Omar , Kim Rockli , Joe William , Subramanian S V
Published: March 2019

Background

In India, excess female under-5 mortality is well documented. Under-5 mortality is also known to be patterned by socioeconomic factors. This study examines sex differentials and sex-specific wealth gradients in neonatal, postneonatal and child mortality in India.

Methods

Repeated cross-sectional study of nationally representative samples of 298 955 children 0–60 months old from the National Family Health Surveys conducted in 2005–2006 and 2015–2016. The study used logistic regression models as well as Cox proportional hazards models.

Results

Overall, boys had greater neonatal mortality than girls and the difference increased between 2005–2006 and 2015–2016. Girls had greater postneonatal and child mortality, but the difference decreased between the surveys and was not statistically significant for child mortality in 2015–2016. A negative wealth gradient was found for all mortality outcomes. Neonatal mortality was persistently greater for boys. Girls had higher child mortality than boys at low levels of wealth and greater postneonatal mortality over much of the wealth distribution. The wealth gradient in neonatal mortality increased between surveys. Females had a stronger wealth gradient than boys for child mortality.

Conclusion

Not distinguishing between neonatal, postneonatal and child mortality masks important gender-specific and wealth-specific disparities in under-5 mortality in India. Substantial gains towards the Sustainable Development Goals can be made by combating neonatal mortality, especially at low levels of wealth. Although impressive improvements have been made in reducing the female disadvantage in postneonatal and child mortality, concerted engagements are necessary to eliminate the gender gap—especially in poor households and in north India.
Predictive factors for HIV infection among men who have sex with men and who are seeking PrEP: a secondary analysis of the PROUD trial
Authors: White Ellen , Dunn David T , Desai Monica , Gafos Mitzy , Kirwan Peter , Sullivan Ann K , Clarke Amanda , McCormack Sheena
Published: March 2019

Objectives

Pre-exposure prophylaxis (PrEP) is a highly effective method of HIV prevention for men who have sex with men (MSM). However, uncertainty remains around the optimal eligibility criteria for PrEP, specifically whether there are subgroups at low risk of HIV for whom PrEP might not be warranted.

Methods

PROUD was an open-label waitlist trial design that randomised MSM attending participating sexual health centres in England to receive PrEP immediately (IMM) or after a deferral period of 1 year (DEF). This analysis is based on participants who were randomised to the deferred arm, when they did not have access to PrEP. HIV incidence was compared between subgroups defined by baseline characteristics.

Results

Overall, 21 participants acquired HIV infection over 239.3 person-years (PY) follow-up, yielding an incidence rate of 8.8/100 PY (95% CI 5.4 to 13.4). Two highly significant predictors for HIV acquisition were identified. Men with a self-reported diagnosis of syphilis, rectal chlamydia (CT) or rectal gonorrhoea (GC) in the previous 12 months had an incidence of 17.2/100 PY (95% CI 9.7 to 28.5); those reporting receptive anal intercourse without a condom (ncRAI) with two or more partners in the previous 3 months had an incidence of 13.6/100 PY (95% CI 7.9 to 21.7). The incidence rate among participants lacking both of these risk factors was 1.1/100 PY (1/87.6, 95% CI 0.03 to 6.4).

Conclusions

The high HIV incidence in PROUD suggests that most participants appropriately judged their need for PrEP. Eligibility criteria for a PrEP programme can therefore be broad, as in the current guidelines. However, a recent history of syphilis or rectal CT/GC, or multiple ncRAI partners indicates a high imminent risk of HIV infection. MSM with any of these characteristics should be offered PrEP as a matter of urgency.