bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of parthanatos on ropivacaine‐induced damage in SH‐SY5Y cells
Authors: Zheng Ting , Zheng Chun‐ying , Zheng Xiao‐chun , Zhao Ruo‐guang , Chen Yan‐qing
Published: January 2017

Ropivacaine is one of the most common but toxic local anaesthetics, and the mechanisms underlying its neurotoxicity are still largely unknown. This study was conducted to prepare a ropivacaine‐induced neuronal injury model and research the effects of ropivacaine on PARP‐1 activation and nicotinamide adenine dinucleotide (NAD)+ depletion. The cell death and apoptosis of ropivacaine‐induced SH‐SY5Y cells were detected with flow cytometry. The lactate dehydrogenase cycling reaction measured the NAD+ level, and western blots were used to analyze the expression levels of PARP‐1 and apoptosis‐inducing factor (AIF) after ropivacaine treatments with different concentrations and durations. A PARP‐1 inhibitor (PJ‐34) was used to confirm the relationship between PARP‐1 activation and NAD+ depletion. Hoechst 33258 nuclear staining and a mitochondrial membrane potential (Δψm) assay were used to detect the role of exogenous NAD+ in ropivacaine‐induced neuronal injury. Ropivacaine‐induced SH‐SY5Y cell death and apoptosis, PARP‐1 activation, and AIF increase as well as intracellular NAD+ depletion occurred in a time‐ and concentration‐dependent manner (P<.05). PARP‐1 activation led to NAD+ depletion (P<.05). Exogenous NAD+ impaired ropivacaine‐induced nuclear injury (P<.05). Ropivacaine treatment induced PARP‐1 activation and NAD+ depletion (P<.05). Parthanatos (PARP‐1‐dependent cell death) was definitely involved in ropivacaine‐induced neuronal injury, and exogenous NAD+ may be a novel therapeutic method for parthanatos‐dependent neuronal injury.
The Negligence Standard: Political Not Metaphysical
Authors: Gardner John
Published: January 2017

This contribution distinguishes two kinds of responsibility: the basic (or ‘metaphysical’) kind that we all inescapably have as functioning human beings; and the assignable (or ‘political’) kind that connects each of us with some particular tasks, and not with others. Having explored some differences between the two, and in particular the role of law's authority in connection with each, the discussion turns to the negligence standard, especially but not only as it figures in tort law. Recently, several philosophers have attempted to find a role for the negligence standard in the metaphysics of basic responsibility. This contribution resists that development and stands up for the traditional lawyer's view that the negligence standard belongs to the pliable politics of assignable responsibility. Basic responsibility, it is argued, is fundamentally strict.
Public‐Private Arbitration and the Public Interest under English Law
Authors: Brekoulakis Stavros , Devaney Margaret
Published: January 2017

Together with the increase in the number of public‐private contracts, recent years have seen a marked proliferation in public‐private arbitrations. This article explores the public interest implications which may arise in such arbitrations and examines how public‐private arbitration is treated under English law. We argue that, due to the lack of a developed administrative law sphere in England and the historical development of arbitration as an exclusively private mode of dispute resolution, the current legal framework of arbitration in England has developed around the private law paradigm of a commercial dispute involving private actors. This private law paradigm results in a conceptual and legal void in respect of how public interest is accounted for, and protected, in arbitrations involving public bodies under English law. Therefore, we suggest that English arbitration law needs to be amended to adequately protect the private interest in public‐private arbitration.
Electoral rules, corruption, inequality and evaluations of democracy
Authors: DONOVAN TODD , KARP JEFFREY
Published: January 2017

Features of electoral systems have been found to have positive effects on evaluations of democracy. This article proposes that there are larger social forces that must be accounted for in such analyses. Using European Social Survey measures of democratic expectations and the ‘satisfaction with democracy’ item, this study tests for effects of electoral rules on perceptions of democracy. It is found that multipartyism/proportionality and preferential ballot structure appear to correspond with positive evaluations of elections and parties, and with greater satisfaction with how democracy is functioning. However, these relationships dissipate when corruption and income inequality are accounted for. This suggests substantial limits to the capacity of electoral reforms to enhance democratic legitimacy. It also suggests that studies of mass perceptions of democratic performance may over‐estimate effects of electoral rules if country‐level corruption and income inequality are not accounted for.
Health Services Utilization in Older Adults with Dementia Receiving Care Coordination: The MIND at Home Trial
Authors: Amjad Halima , Wong Stephanie K. , Roth David L. , Huang Jin , Willink Amber , Black Betty S. , Johnston Deirdre , Rabins Peter V. , Gitlin Laura N. , Lyketsos Constantine G. , Samus Quincy M.
Published: January 2017

Objective

To investigate effects of a novel dementia care coordination program on health services utilization.

Data Sources/Study Setting

A total of 303 community‐dwelling adults aged ≥70 with a cognitive disorder in Baltimore, Maryland (2008–2011).

Study Design

Single‐blind RCT evaluating efficacy of an 18‐month care coordination intervention delivered through community‐based nonclinical care coordinators, supported by an interdisciplinary clinical team.

Data Collection/Extraction Methods

Study partners reported acute care/inpatient, outpatient, and home‐ and community‐based service utilization at baseline, 9, and 18 months.

Principal Findings

From baseline to 18 months, there were no significant group differences in acute care/inpatient or total outpatient services use, although intervention participants had significantly increased outpatient dementia/mental health visits from 9 to 18 months (p = .04) relative to controls. Home and community‐based support service use significantly increased from baseline to 18 months in the intervention compared to control (p = .005).

Conclusions

While this dementia care coordination program did not impact acute care/inpatient services utilization, it increased use of dementia‐related outpatient medical care and nonmedical supportive community services, a combination that may have helped participants remain at home longer. Future care model modifications that emphasize delirium, falls prevention, and behavior management may be needed to influence inpatient service use.
Sheep Milk: Physicochemical Characteristics and Relevance for Functional Food Development
Authors: Balthazar C.F. , Pimentel T.C. , Ferrão L.L. , Almada C.N. , Santillo A. , Albenzio M. , Mollakhalili N. , Mortazavian A.M. , Nascimento J.S. , Silva M.C. , Freitas M.Q. , Sant’Ana A.S. , Granato D. , Cruz A.G.
Published: January 2017

Sheep milk has a high nutritional value and high concentrations of proteins, fats, minerals, and vitamins, as compared to the milks of other domestic species. The physicochemical and nutritional characteristics of sheep milk can be advantageous for the manufacture of products containing prebiotic ingredients and/or probiotic bacteria, which are major categories in the functional food market. Following this technological trend, this review will address the characteristics and advantages of sheep milk as a potentially functional food, as well as the development of sheep milk dairy products containing prebiotics and/or probiotics.
Good Governance in the Bioeconomy
Authors: Devaney Laura , Henchion Maeve , Regan Áine
Published: January 2017

In response to growing societal and environmental challenges, the concept of the bioeconomy has emerged in Europe, shifting society away from fossil fuels to utilising renewable biological resources to meet food, feed, fuel and material needs. The bioeconomy poses unique questions for governing stakeholders, with a need to simultaneously consider issues of food, fuel and resource security, competition for biomass supply, environmental degradation, climate change, economic growth and rural development. It thus represents one of the most politically complex areas facing agri‐food and rural resource sectors internationally. Further development of the bioeconomy and its impact on society will depend on how it is governed. It is widely accepted that good governance will require input from a diverse range of stakeholders beyond traditional government intervention. In this article, we explore the application of good governance principles as a common set of objectives for European stakeholders to strive towards, with particular consideration given to the principles of accountability and participation. How these elements need to be addressed as a priority for the economic, environmental and social sustainability of the future European bioeconomy is highlighted.
Yeast's balancing act between ethanol and glycerol production in low‐alcohol wines
Authors: Goold Hugh D. , Kroukamp Heinrich , Williams Thomas C. , Paulsen Ian T. , Varela Cristian , Pretorius Isak S.
Published: January 2017

Alcohol is fundamental to the character of wine, yet too much can put a wine off‐balance. A wine is regarded to be well balanced if its alcoholic strength, acidity, sweetness, fruitiness and tannin structure complement each other so that no single component dominates on the palate. Balancing a wine's positive fruit flavours with the optimal absolute and relative concentration of alcohol can be surprisingly difficult. Over the past three decades, consumers have increasingly demanded wine with richer and riper fruit flavour profiles. In response, grape and wine producers have extended harvest times to increase grape maturity and enhance the degree of fruit flavours and colour intensity. However, a higher degree of grape maturity results in increased grape sugar concentration, which in turn results in wines with elevated alcohol concentration. On average, the alcohol strength of red wines from many warm wine‐producing regions globally rose by about 2% (v/v) during this period. Notwithstanding that many of these ‘full‐bodied, fruit‐forward’ wines are well balanced and sought after, there is also a significant consumer market segment that seeks lighter styles with less ethanol‐derived ‘hotness’ on the palate. Consumer‐focussed wine producers are developing and implementing several strategies in the vineyard and winery to reduce the alcohol concentration in wines produced from well‐ripened grapes. In this context, Saccharomyces cerevisiae wine yeasts have proven to be a pivotal strategy to reduce ethanol formation during the fermentation of grape musts with high sugar content (> 240 g l−1). One of the approaches has been to develop ‘low‐alcohol’ yeast strains which work by redirecting their carbon metabolism away from ethanol production to other metabolites, such as glycerol. This article reviews the current challenges of producing glycerol at the expense of ethanol. It also casts new light on yeast strain development programmes which, bolstered by synthetic genomics, could potentially overcome these challenges.
Whole genome sequencing analysis of lung adenocarcinoma in Xuanwei, China
Authors: Wang Xiao , Li Jing , Duan Yong , Wu Huifei , Xu Qiuyue , Zhang Yanliang
Published: January 2017

Background

The lung cancer mortality rate in Xuanwei city is among the highest in China and adenocarcinoma is the major histological type. Lung cancer has been associated with exposure to indoor smoky coal emissions that contain high levels of polycyclic aromatic hydrocarbons; however, the pathogenesis of lung cancer has not yet been fully elucidated.

Methods

We performed whole genome sequencing with lung adenocarcinoma and corresponding non‐tumor tissue to explore the genomic features of Xuanwei lung cancer. We used the Molecule Annotation System to determine and plot alterations in genes and signaling pathways.

Results

A total of 3 428 060 and 3 416 989 single nucleotide variants were detected in tumor and normal genomes, respectively. After comparison of these two genomes, 977 high‐confidence somatic single nucleotide variants were identified. We observed a remarkably high proportion of C·G‐A·T transversions. HECTD4, RCBTB2, KLF15, and CACNA1C may be cancer‐related genes. Nine copy number variations increased in chromosome 5 and one in chromosome 7. The novel junctions were detected via clustered discordant paired ends and 1955 structural variants were discovered. Among these, we found 44 novel chromosome structural variations. In addition, EGFR and CACNA1C in the mitogen‐activated protein kinase signaling pathway were mutated or amplified in lung adenocarcinoma tumor tissue.

Conclusion

We obtained a comprehensive view of somatic alterations of Xuanwei lung adenocarcinoma. These findings provide insight into the genomic landscape in order to further learn about the progress and development of Xuanwei lung adenocarcinoma.
Differentiating the Effects of Familial Risk for Alcohol Dependence and Prenatal Exposure to Alcohol on Offspring Brain Morphology
Authors: Sharma Vinod K. , Hill Shirley Y.
Published: January 2017

Background

Offspring with a family history of alcohol dependence (AD) have been shown to have altered structural and functional integrity of corticolimbic brain structures. Similarly, prenatal exposure to alcohol is associated with a variety of structural and functional brain changes. The goal of this study was to differentiate the brain gray matter volumetric differences associated with familial risk and prenatal exposure to alcohol among offspring while controlling for lifetime personal exposures to alcohol and drugs.

Methods

A total of 52 high‐risk (HR) offspring from maternal multiplex families with a high proportion of AD were studied along with 55 low‐risk (LR) offspring. Voxel‐based morphometric analysis was performed using statistical parametric mapping (SPM8) software using 3T structural images from these offspring to identify gray matter volume differences associated with familial risk and prenatal exposure.

Results

Significant familial risk group differences were seen with HR males showing reduced volume of the left inferior temporal, left fusiform, and left and right insula regions relative to LR males, controlling for prenatal exposure to alcohol drugs and cigarettes. HR females showed a reduction in the right fusiform but also showed a reduction in volume in portions of the cerebellum (left crus I and left lobe 8). Prenatal alcohol exposure effects, assessed within the familial HR group, was associated with reduced right middle cingulum and left middle temporal volume. Even low exposure resulting from mothers drinking in amounts less than the median of those who drank (53 drinks or less over the course of the pregnancy) showed a reduction in volume in the right anterior cingulum and in the left cerebellum (lobes 4 and 5).

Conclusions

Familial risk for AD and prenatal exposure to alcohol and other drugs show independent effects on brain morphology.
Ethanol Induces Platelet Apoptosis
Authors: Liu Lei , Chen Mengxing , Zhao Lili , Zhao Qing , Hu Renping , Zhu Jie , Yan Rong , Dai Kesheng
Published: January 2017

Background

Alcohol abuse incurs severe medical conditions, such as thrombocytopenia and hemorrhage, but the pathogenesis is not totally understood. Alcohol has been reported to induce apoptosis in eukaryotic cells, such as hepatocyte, nerve cell, corneal fibroblasts. However, it is still unclear whether alcohol induces platelet apoptosis.

Methods

Washed human platelets were pretreated with ethanol (EtOH), and apoptotic events and platelet function were detected. In in vivo experiments, C57BL/6J mice were given EtOH by gavage. Platelet counts, tail bleeding time, and the stomach were examined.

Results

EtOH dose dependently induces depolarization of mitochondrial inner transmembrane potential, up‐regulation of Bax, down‐regulation of Bcl‐2, and caspase‐3 activation. EtOH does not induce surface expression of P‐selectin or PAC‐1 binding, whereas significantly reduces collagen‐, thrombin‐, and ADP‐induced platelet aggregation. Moreover, EtOH induces c‐Jun NH2‐terminal kinase activation. In an in vivo mouse model of the acute alcoholism, EtOH significantly reduces the number of circulating platelets, prolongs the tail bleeding time, and causes gastric mucosa hemorrhage.

Conclusions

These data demonstrate that EtOH induces mitochondria‐mediated intrinsic platelet apoptosis, results in the reduction of the number of circulating platelets, and impairs in vivo hemostasis. These findings reveal the possible pathogenesis of hemorrhagic symptoms in patients experiencing acute alcohol intoxication.
Screening, brief intervention and referral to treatment (SBIRT): implementation barriers, facilitators and model migration
Authors: Vendetti Janice , Gmyrek Amanda , Damon Donna , Singh Manu , McRee Bonnie , Del Boca Frances
Published: January 2017

Aims

To identify barriers and facilitators associated with initial implementation of a US alcohol and other substance use Screening, Brief Intervention, and Referral to Treatment (SBIRT) grant program, and to identify modifications in program design that addressed implementation challenges.

Design

A mixed‐method approach used quantitative and qualitative data, including SBIRT provider ratings of implementation barriers and facilitators, staff interview responses and program documentation.

Setting

Multiple sites within the first seven programs funded in a national demonstration program in the United States.

Participants

One hundred and two SBIRT providers were surveyed; 221 SBIRT stakeholders and staff were interviewed.

Measurements

Mean ratings of barriers and facilitators were calculated using provider survey responses. An inductive content analysis of interview responses identified factors perceived to support and challenge implementation; program modifications that occurred over time were recorded.

Findings

Providers rated pre‐selected implementation facilitators higher than barriers. Content analysis of interview responses revealed six themes: committed leaders; intra‐ and inter‐organizational communication/collaboration; provider buy‐in and model acceptance; contextual factors; quality assurance; and grant requirements. Over time, programs tended to: adopt more efficient ‘pre‐screen’ item sets; screen for risk factors in addition to alcohol/substance use; use contracted specialists to deliver SBIRT services; conduct services in high‐volume emergency department and trauma center settings; and implement on‐site and telephonic treatment delivery.

Conclusions

Screening, Brief Intervention and Referral to Treatment program implementation in the United States is facilitated by committed leadership and the use of substance use specialists, rather than medical generalists, to deliver services. Many implementation challenges can be addressed by an adequate start‐up phase focused on comprehensive education and training, and on the development of intra‐ and inter‐organizational communication and collaboration; opinion leader support; and practitioner and host site buy‐in.
The SBIRT program matrix: a conceptual framework for program implementation and evaluation
Authors: Del Boca Frances K. , McRee Bonnie , Vendetti Janice , Damon Donna
Published: January 2017

Background and Aims

Screening, Brief Intervention and Referral to Treatment (SBIRT) is a comprehensive, integrated, public health approach to the delivery of services to those at risk for the adverse consequences of alcohol and other drug use, and for those with probable substance use disorders. Research on successful SBIRT implementation has lagged behind studies of efficacy and effectiveness. This paper (1) outlines a conceptual framework, the SBIRT Program Matrix, to guide implementation research and program evaluation and (2) specifies potential implementation outcomes.

Methods

Overview and narrative description of the SBIRT Program Matrix.

Results

The SBIRT Program Matrix has five components, each of which includes multiple elements: SBIRT services; performance sites; provider attributes; patient/client populations; and management structure and activities. Implementation outcomes include program adoption, acceptability, appropriateness, feasibility, fidelity, costs, penetration, sustainability, service provision and grant compliance.

Conclusions

The Screening, Brief Intervention and Referral to Treatment Program Matrix provides a template for identifying, classifying and organizing the naturally occurring commonalities and variations within and across SBIRT programs, and for investigating which variables are associated with implementation success and, ultimately, with treatment outcomes and other impacts.
Screening, Brief Intervention and Referral to Treatment: implications of SAMHSA's SBIRT initiative for substance abuse policy and practice
Authors: Babor Thomas F. , Del Boca Frances , Bray Jeremy W.
Published: January 2017

Aims

This paper describes the major findings and public health implications of a cross‐site evaluation of a national Screening, Brief Intervention and Referral to Treatment (SBIRT) demonstration program funded by the US Substance Abuse and Mental Health Services Administration (SAMHSA).

Methods

Eleven multi‐site programs in two cohorts of SAMHSA grant recipients were each funded for 5 years to promote the adoption and sustained implementation of SBIRT. The SBIRT cross‐site evaluation used a multi‐method evaluation design to provide comprehensive information on the processes, outcomes and costs of SBIRT as implemented in a variety of medical and community settings.

Findings

SBIRT programs in the two evaluated SAMHSA cohorts screened more than 1 million patients/clients. SBIRT implementation was facilitated by committed leadership and the use of substance use specialists, rather than medical generalists, to deliver services. Although the quasi‐experimental nature of the outcome evaluation does not permit causal inferences, pre–post differences were clinically meaningful and statistically significant for almost every measure of substance use. Greater intervention intensity was associated with larger decreases in substance use. Both brief intervention and brief treatment were associated with positive outcomes, but brief intervention was more cost‐effective for most substances. Sixty‐nine (67%) of the original performance sites adapted and redesigned SBIRT service delivery after initial grant funding ended. Four factors influenced SBIRT sustainability: presence of program champions, availability of funding, systemic change and effective management of SBIRT provider challenges.

Conclusions

The US Substance Abuse and Mental Health Services Administration's Screening, Brief Intervention and Referral to Treatment (SBIRT) demonstration program was adapted successfully to the needs of early identification efforts for hazardous use of alcohol and illicit drugs. SBIRT is an innovative way to integrate the management of substance use disorders into primary care and general medicine. Screening, Brief Intervention and Referral to Treatment implementation was associated with improvements in treatment system equity, efficiency and economy.
Comparison of apical centring ability between incisal‐shifted access and traditional lingual access for maxillary anterior teeth
Authors: Yahata Yoshio , Masuda Yoshiko , Komabayashi Takashi
Published: January 2017

The aim of this study was to compare the apical centring ability of incisal‐shifted access (ISA) with that of traditional lingual access (TLA). Fifteen three‐dimensional printed resin models were prepared from the computed tomography data for a human maxillary central incisor and divided into ISA (n = 7), TLA (n = 7) and control (n = 1) groups. After access preparation, these models were shaped to the working length using K‐files up to #40, followed by step‐back procedures. An apical portion of the model was removed at 0.5 mm coronal to the working length. Microscopic images of each cutting surface were taken to measure the preparation area and the distance of transportation. TLA created a larger preparation area than ISA (P < 0.05). The distance of transportation (mean ± standard deviation) was 0.4 ± 0.1 mm for ISA and 0.7 ± 0.1 mm for TLA (P < 0.05). Access cavity preparation has a significant effect on apical centring ability. ISA is beneficial to maintaining apical configuration.
Feeding behaviour and survival of Bacillus thuringiensis‐resistant and Bacillus thuringiensis‐susceptible larvae of Helicoverpa armigera (Lepidoptera: Noctuidae) exposed to a diet with Bacillus thuringiensis toxin
Authors: Luong Tuyet T A , Zalucki Myron P , Perkins Lynda E , Downes Sharon J
Published: January 2017

Although higher than expected numbers of surviving larvae of Helicoverpa spp. are reported in some Bollgard II cotton fields from time to time, there is no convincing evidence that field resistance has developed. A behavioural component, specifically the avoidance of the toxin, was considered to contribute to larvae surviving on Bacillus thuringiensis (Bt) toxin‐expressing plants. Experiments were conducted with Bt‐susceptible and Bt‐resistant larvae of Helicoverpa armigera to investigate (1) how larval responses to food deprivation might lead to differences in survival and therefore how far neonates could move to find a suitable feeding site and (2) whether larvae that are physiologically susceptible vs. resistant behave differently when feeding on diet with Bt and without Bt toxins. Bt‐susceptible neonates of H. armigera, which were significantly heavier, could survive without food for longer and recover better than Bt‐resistant neonates. Although H. armigera neonates did not shift their behaviour with respect to Bt toxin on artificial diet before their first feeding event, the tendency of Bt‐susceptible larvae to remain on non‐Bt diet and move off Bt diet may allow them to survive in a Bt environment. This behaviour resulted in a higher percentage of survival in situations where a diet choice was offered.
RAIFFEISEN AS SOCIAL INNOVATOR
Authors: FAIRBAIRN Brett
Published: January 2017

In recent years the term social innovation has become widely used by policy makers, yet important ambiguities remain. One of these concerns what has been called the paradox of embedded agency – how social innovators conceive of something new when working with existing social institutions. So far few writers have considered whether historical examples can, with benefit of hindsight, shed light on the relationships between social innovators and social institutions. This paper considers the example of Friedrich Wilhelm Raiffeisen, creator of rural credit unions and agricultural co‐operatives in 19th‐century Germany. Raiffeisen was a social conservative who worked in many ways within existing social institutions. At the same time, his desire to meet social needs drove him to create new forms of action and organization that resulted in social innovation. Raiffeisen's process of invention shows that social innovation, particularly in transitional eras like his, need not be a matter of using logical‐deductive processes to address a social need, but may depend critically on values, will, a readiness to experiment, and an ability to find allies. These qualities enabled Raiffeisen to break through existing institutions to do something fundamentally new, and they may be qualities that provide new focus for social‐innovation research and policy.
Genetic Influences of OPRM1,OPRD1 and COMT on Morphine Analgesia in a Multi‐Modal, Multi‐Tissue Human Experimental Pain Model
Authors: Nielsen Lecia M. , Christrup Lona L. , Sato Hiroe , Drewes Asbjørn M. , Olesen Anne E.
Published: January 2017

Human studies on experimentally induced pain are of value to elucidate the genetic influence on morphine analgesia under controlled conditions. The aim of this study was to investigate whether genetic variants of mu‐, kappa‐ and delta‐opioid receptor genes (OPRM1, OPRK1 and OPRD1) and catechol‐O‐methyltransferase gene (COMT) are associated with the morphine analgesia. The study was a randomized, double‐blind, two‐way, crossover, single‐dose study conducted in 40 healthy participants, where morphine was compared with placebo. Pain was induced by contact heat, muscle pressure, bone pressure, rectal stimulations (mechanical, electrical and thermal) and cold pressor test (immersion of the hand into ice water). Sixteen genetic polymorphisms of four candidate genes were explored. Variability in morphine analgesia to contact heat stimulation was associated with COMT rs4680 (p = 0.04), and rectal thermal stimulation was associated with OPRM1 rs9479757 (p = 0.03). Moreover, in males, variability in morphine analgesia to rectal thermal stimulation was associated with OPRD1 polymorphisms: rs2234918 (p = 0.01) and rs533123 (p = 0.046). The study was explorative and hypothesis‐generating due to the relatively small study size. However, results suggest that genetic variants in the COMT and OPRM1 irrespective of gender, and OPRD1 in males may contribute to the variability in morphine analgesia in experimental pain models.
Lithiumeter: Version 2.0
Authors: Malhi Gin S. , Gershon Samuel , Outhred Tim
Published: January 2017

Background

The Lithiumeter was developed as a visual and practical guide for determining lithium levels in the management of bipolar disorder (BD). It appears to have been well received, as evidenced by its increasing popularity amongst doctors as a deskside clinical aide, and adoption and reproduction of the schematic in clinical guidelines and texts. However, since its publication 5 years ago, key basic neuroscience and clinical research developments pertaining to lithium have significantly advanced our understanding, necessitating further refinement of guidance concerning the practicalities of lithium therapy.

Methods

Literature concerning the indications for, and therapeutic levels of, lithium and the associated acute and chronic risks of therapy was scrutinized as part of updating clinical practice guidelines. We have reviewed these updates and identified significant areas of change with respect to the previous Lithiumeter (version 1.0).

Results

Since 2011, updated clinical practice guidelines have narrowed the indicated plasma lithium concentration for maintenance therapy, suggesting that additional guidance is necessary for optimizing treatment. Relevant updated clinical guidance was integrated to constitute the Lithiumeter 2.0, which provides a more comprehensive overview of the practical aspects of lithium therapy while maintaining a focus on optimization of lithium levels, such as differential titration of lithium depending on the current mood state.

Conclusions

The Lithiumeter 2.0 is an update that clinicians will find useful for their practice. By addressing some of the issues faced in clinical practice, translational clinical research will continue to inform the Lithiumeter in future updates.
The Social Value of Pragmatic Trials
Authors: Kalkman Shona , van Thiel Ghislaine , van der Graaf Rieke , Zuidgeest Mira , Goetz Iris , Grobbee Diederick , van Delden Johannes
Published: January 2017

Pragmatic trials aim to directly inform health care decision‐making through the collection of so‐called ‘real world data’ from observations of comparative treatment effects in clinical practice. In order to ensure the applicability and feasibility of a pragmatic trial, design features may be necessary that deviate from standard research ethics requirements. Examples are traditional requirements to seek written informed consent and to perform extensive data and safety monitoring. Proposals for deviations from standard research ethics practice have resulted in controversy about their ethical acceptability. One of the justifications for altered procedures is the allegedly high social value of pragmatic trials. In order to properly operationalize the concept in the ethical assessment of pragmatic trial designs, specification is warranted. We identified three determinants from common claims about a pragmatic trial's social value: (1) the extent to which the research question has real world relevance, (2) the trial design's ability to generate a real world answer and (3) the probability of direct uptake of the results by decision‐makers in practice. Subsequently, we discuss how these determinants should be applied to the practice of pragmatic trials, and to what extent they might be applicable to explanatory trials.
The Social Value of Knowledge and the Responsiveness Requirement for International Research
Authors: Wenner Danielle M.
Published: January 2017

Ethicists have long recognized that two necessary features of ethical research are scientific validity and social value. Yet despite a significant literature surrounding the validity component of this dictate, until recently there has been little attention paid to unpacking what the social value component might require. This article introduces a framework for assessing the social value of research, and in particular, for determining whether a given research program is likely to have significant social value of the kind necessary to fulfill the social value requirement. The article goes on to illustrate how this framework can provide a clearer account of the responsiveness requirement, an ethical dictum that is oft‐repeated but whose content and value as a guideline in international research remains contested. Although I introduce this conception of social value in the context of the responsiveness requirement, the account offered can, and is intended to, stand alone as a tool for the assessment of the social value of research. As such it can be usefully applied to discussions about the value of comparative effectiveness trials, the assessment of the continued proliferation of me‐too drugs and the research done to develop them, the demand for public access to study‐generated data, and persistent deficits in the publication of negative results.
Selection of Effects in Cox Frailty Models by Regularization Methods
Authors: Groll Andreas , Hastie Trevor , Tutz Gerhard
Published: January 2017

In all sorts of regression problems, it has become more and more important to deal with high-dimensional data with lots of potentially influential covariates. A possible solution is to apply estimation methods that aim at the detection of the relevant effect structure by using penalization methods. In this article, the effect structure in the Cox frailty model, which is the most widely used model that accounts for heterogeneity in survival data, is investigated. Since in survival models one has to account for possible variation of the effect strength over time the selection of the relevant features has to distinguish between several cases, covariates can have time-varying effects, time-constant effects, or be irrelevant. A penalization approach is proposed that is able to distinguish between these types of effects to obtain a sparse representation that includes the relevant effects in a proper form. It is shown in simulations that the method works well. The method is applied to model the time until pregnancy, illustrating that the complexity of the influence structure can be strongly reduced by using the proposed penalty approach.
Late surgical correction of hypospadias increases the risk of complications: a series of 501 consecutive patients
Authors: Garnier Sarah , Maillet Olivier , Cereda Barbara , Ollivier Margot , Jeandel Clement , Broussous Sylvie , Lopez Christophe , Paris Francoise , Philibert Pascal , Amouroux Cyril , Jeandel Claire , Coffy Amandine , Gaspari Laura , Daures Jean Pierre , Sultan Charles , Kalfa Nicolas
Published: January 2017

Objectives

To evaluate the outcomes of hypospadias surgery according to age and to determine if some complications are age‐related.

Patients and Methods

This retrospective study was based on 722 boys with hypospadias undergoing primary repair. A total of 501 boys underwent urethroplasty and were included in the study. Complications requiring an additional procedure (stenosis, fistula, dehiscence, relapse of curvature, urethrocele) were included in the analysis, as well as healing problems, infections, haematomas and detrusor‐sphincter dyssynergy. Logistic regression analysis was performed.

Results

Hypospadias was anterior in 63.1%, mid‐penile in 20.5%, posterior in 8.4% and scrotal in 7.9% of the boys. The median (range) age was 4 (1–16) years. The overall rates of re‐intervention and complications were 22.8% and 36.2%, respectively. Age >2 years was a significant predictor of complications (P = 0.002, odds ratio 1.98 [95% confidence interval 1.26–3.13]). Some periods of time appeared to be associated with a specific complication: dyssynergy was more common between the ages of 24 and 36 months (12.5 vs 3.6%; P = 0.01) and healing problems

were more common in boys aged >13 years (1.5 vs 28.5%; P = 0.06).

Conclusion

Delayed surgery may be detrimental for patients. Factors related to age may influence the rate of complications. After the age of 2 years, urethral surgery may interfere with the normal toilet‐training process. During puberty, endogenous testosterone may alter healing. Even if no specific data exist for severe hypospadias, it may be prudent to continue to advocate early surgery in patients with disorders of sex development.
Molecular subtypes of colorectal cancers determined by PCR‐based analysis
Authors: Sugai Tamotsu , Eizuka Makoto , Takahashi Yayoi , Fukagawa Tomoyuki , Habano Wataru , Yamamoto Eiichiro , Akasaka Risaburo , Otuska Kouki , Matsumoto Takayuki , Suzuki Hiromu
Published: January 2017

Tumor tissue consists of a heterogeneous cell population. The allelic imbalance (AI) ratio, determined in isolated tumor glands, is a good index of tumor heterogeneity. However, associations of the patterns of AI and microsatellite instability (MSI) development, observed in most cases of colorectal cancer (CRC), with tumor progression have not been reported previously. In this study, we examined whether CRC genetic profiles stratified by a combination of the AI ratio and MSI facilitate categorization of CRC, and whether these genetic profiles are associated with specific molecular alterations in CRC. A crypt isolation method was used to isolate DNA from tumors and normal glands obtained from 147 sporadic CRCs. AI and MSI statuses were determined using PCR‐based microsatellite analysis and stratified based on AI ratio and MSI status. DNA methylation status (high methylation, intermediate methylation and low methylation status and mutations in KRAS, BRAF, and TP53 were examined. In addition, mucin markers were immunostained. Based on this analysis, four subgroups were categorized. Subgroup 1 was characterized by a high MSI status and BRAF mutation; subgroup 2 was closely associated with a high AI ratio, which accumulated during the early phases of colorectal carcinogenesis, and TP53 mutation; subgroup 3 was associated with a low AI ratio, seen during the later phases of colorectal carcinogenesis, and KRAS mutation; and subgroup 4 was defined as a minor subgroup. These results confirmed that classification of distinct molecular profiles provides important insights into colorectal carcinogenesis.
Board member monitoring behaviors in credit unions: The role of conscientiousness and identification with shareholders
Authors: Guerrero Sylvie , Lapalme Marie‐Ève , Herrbach Olivier , Séguin Michel
Published: January 2017

Research Question/Issue

This research investigates the antecedents of board members’ monitoring behaviors at the individual level. The main idea is that individuals who are both conscientious and identified with shareholders are those most likely to adopt monitoring behaviors.

Research Findings/Insights

The study was conducted using a survey of 166 board members of a large Canadian credit union corporation. Data on monitoring behaviors were collected directly from the chairpersons of the boards they participate in. The results validate the hypothesized moderated mediation model in which perceived importance of monitoring by board members mediates the relationship between conscientiousness and actual monitoring behaviors, on the one hand, and identification with shareholders moderates the relationship between conscientiousness and the perception of the importance of monitoring, on the other hand.

Theoretical/Academic Implications

By investigating the mediating effect of the perceived importance of the monitoring role in the relationship between conscientiousness and monitoring behaviors, our study provides an empirical test of the attention‐based view in the context of boards of directors and thus contributes to opening the ‘black box’ of board behaviors. Further, by looking at the interactive effect of conscientiousness and identification with shareholders, our study brings new insights into the motivational drivers of directors’ monitoring behaviors.

Practitioner/Policy Implications

This study invites practitioners in charge of board members’ recruitment and selection to reconsider their practices in order to target individuals demonstrating high levels of conscientiousness. It also highlights the importance of implementing board cultures that value conscientiousness and emphasize shareholders’ interests.
Snoring and components of metabolic syndrome in Southeastern Chinese adults: A community‐based study
Authors: Huang Jianchai , Qi Jiachao , Lin Qichang , Li Shuqi , Chen Gongping , Ding Haibo , Zhao Jianming
Published: January 2017

Introduction

Snoring has been associated with a number of abnormal conditions, but little work has been done on its association with components of metabolic syndrome based on the epidemiology in Chinese adults.

Objective

This study aimed to investigate the association between snoring and components of metabolic syndrome in southeastern Chinese adults.

Methods

A two‐stage, cross‐sectional community‐based study was performed in Fuzhou, Southeast China, from 2005 to 2009. Stage 1: 5500 subjects were administered a questionnaire. Data on self‐reported snoring status, daytime somnolence, demographic data, disease histories, and potential confounders were collected and anthropometric measurements were performed. Stage 2: 1000 subjects who were already investigated underwent a blood test and measurement of blood pressure.

Results

Data from 4286 subjects were available; 606 subjects were habitual snorers. The prevalence of overweight or obesity, hyperglycemia, hypertension, and dyslipidemia in occasional and habitual snorers was higher than that in the study population (16.66%, 7.89%, 10.52%, and 5.81%, respectively). A significantly increasing trend based on snoring frequency existed in the prevalence of metabolic disorders. The prevalence of components of metabolic syndrome continued to be significantly associated with snoring frequency after controlling confounding factors. Odds ratios of suffering from the aforementioned conditions for occasional and habitual snorers were 1.5–2.5 (P < 0.05) and 2.4–4.8 (P < 0.001) times higher, respectively, compared with nonsnorers.

Conclusions

The prevalence of snoring and components of metabolic syndrome is high in southeastern Chinese adults. Both habitual and occasional snoring are closely associated with metabolic disorders independent of confounding factors.
Nephrectomy‐induced reduced renal function and the health‐related quality of life of living kidney donors
Authors: Han Xiao , Lim Joel Yu Ming , Raman Lata , Tai Bee Choo , Kaur Hersharan , Goh Angeline Ting Hui , Vathsala Anantharaman , Tiong Ho Yee
Published: January 2017

Objective

To evaluate the health impact of nephrectomy on living kidney donors (LKDs) by comparing the health‐related quality of life (HrQOL) scores measured by Short Form‐36 (SF36) between those with and without postdonation renal function impairment (PRFI).

Methods

Eighty‐two LKDs (47 females, mean age=50.2±11.2 years) were prospectively recruited to participate in a SF‐36 HrQOL survey. Chart review, individual baseline, and postoperative renal function (eGFR) was determined using the Modification of Diet in Renal Disease formula. PRFI was defined as eGFR<60 mL/min/1.73 m2 or proteinuria. Mean SF‐36 domain scores were compared between those with and without PRFI.

Results

After a median follow‐up of 5.7 years, the prevalence of postdonation comorbidities was 29.3% (n=24) PRFI, 25.6% (n=21) hypertension, 6.1% (n=5) diabetes, and 3.7% (n=3) heart disease, and no LKDs developed end‐stage renal disease. Mean eGFR before and after donor nephrectomy was 95.5±23.4 and 71.0±17.3 mL/min/1.73 m2 (P<.01). Mean SF‐36 scores of LKDs were not significantly different between those with and without PRFI in all the domains (all P>.05). Similarly, the proportion of LKDs with PRFI did not differ significantly between the patients with SF‐36 domain scores above and below the published reference values.

Conclusion

Nephrectomy‐induced PRFI may not have a significant impact on the HrQOL of the LKD population with a low proportion of other major comorbidities such as diabetes and ischemic heart disease.
A Moral Economy of Water: Charity Wells in Egypt's Nile Delta
Authors: ElDidi Hagar , Corbera Esteve
Published: January 2017

Though commonly viewed as a human right, access to water is often difficult and highly unequal within and between communities, depending on various social and power relations, access mechanisms and property rights regimes. However, moral norms and subsistence ethics can also play a balancing role, enhancing access to water for vulnerable groups and individuals, particularly in contexts of water scarcity. Using the example of a Nile Delta village, this article explores the role of charitable water wells (sobol) in influencing both irrigation and drinking water access relations, by understanding their different modes of governance and the motivations behind their emergence. The article argues that charitable norms underlying sobol are dynamic. They stem from certain moral ideologies concerning religion, property and reciprocity, and while they do greatly enhance access to water, it is with varying degrees, limitations and remaining access discrepancies. Sobol alter property rights relations, extending entitlements to water, but their effectiveness is also limited by existing property rights regimes. Sobol are also limited by existing anti‐cooperative actions, and being embedded in an inequitable access system, they may not fully counterbalance inequitable water access. The limitations of cooperative water access arrangements should be counterweighed and complemented by overarching and equitable water distribution systems.
Engendering the New Enclosures: Development, Involuntary Resettlement and the Struggles for Social Reproduction in Coastal Tanzania
Authors: Brigitte Chung Youjin
Published: January 2017

This article engages with the feminist concept of ‘social reproduction’ to arrive at a richer understanding of the gendered processes and outcomes of contemporary large‐scale land acquisitions, or the ‘new enclosures’. It focuses on the case of a recent land deal for industrial sugarcane production in the Coast Region of Tanzania and the resultant process of involuntary resettlement. It critically analyses people's struggles for land in the face of imminent displacement, and the gendered ways they experience the erosion of their pre‐existing modes of social reproduction. It argues that enclosure of rural landscapes does more than immediately strip peasants and pastoralists of their means of production and turn them into wage labourers. It gradually uproots them from their socio‐ecological knowledges, cultural practices and historical memories, which are rooted on the land and articulated through gender. The highly uncertain processes of enclosure and displacement also force rural women and men to renegotiate their livelihood strategies and intra‐household gender relations.