bluuebunny/crossref_metadata_2025 huggingface dataset:
The half‐life and exposure of cefuroxime varied in newborn infants after a Caesarean section
Authors: Zachariassen G , Hyldig N , Joergensen JS , Nielsen DS , Greisen G
Published: May 2016

Aim

No information was available on how fast intravenous cefuroxime administered to pregnant women before a Caesarean section was cleared in newborn infants. This study investigated the drug's half‐life and the exposure of healthy newborn infants after their mothers received the drug.

Methods

Healthy mothers received a single dose of cefuroxime 15–60 minutes before skin incision. One blood sample was drawn from the umbilical cord, and two blood samples were drawn from the infant after delivery. Total plasma cefuroxime (μg/mL) was measured using high‐pressure liquid chromatography.

Results

Cefuroxime was given to 22 mothers, including two who had twins. The concentration of cefuroxime varied significantly among infants (p < 0.001), while the rate of decline did not (p = 0.24). The median cefuroxime half‐life was 3.5 hours (range 2.9–5.5), which was approximately three times longer than in normal adults and seemed to clear within 24 hours. The median area under the concentration–time curve was 65.0 hour μg/mL (range 31.7–162.4).

Conclusion

We found that the cefuroxime half‐life after a Caesarean section varied among infants and was longer than in normal adults but cleared within 24 hours. Exposure to cefuroxime in newborn infants may influence the gut microbiota and should be investigated further.
Characteristics and outcomes of critically ill children following emergency transport by a specialist paediatric transport team
Authors: Hamrin Tova Hannegård , Berner Jonas , Eksborg Staffan , Radell Peter J. , Fläring Urban
Published: May 2016

Aim

We compared acute patients admitted to a single paediatric intensive care unit (PICU) following an emergency transfer by a specialist paediatric transport team and by other routes.

Methods

This was a retrospective descriptive register‐based study of consecutive admissions to a tertiary PICU in Sweden from 1 January 2008 to 31 December 2013. We compared the general characteristics of the cohorts, together with predicted death rates (PDR), PICU mortality, 30‐day mortality, PICU length of stay (PICU LOS) and resource use.

Results

Of the 3665 nonelective admissions, 221 patients received emergency transport from referring hospitals to the PICU by the specialist paediatric transport team. Their median age was lower (146 versus 482 days), PDR was higher (5.58% versus 1.39%), PICU LOS was longer (4.24 days versus 1.06 days), and they received more PICU‐specific therapies. The standardised mortality ratio did not differ between the cohorts, and the PICU mortality was lower than predicted in both groups. The transport distance and mode of transport did not influence survival.

Conclusion

Children admitted to the PICU following emergency transfers by the specialist paediatric transport team were younger, sicker, received more PICU‐specific therapies and had longer PICU LOS than other acutely admitted critically ill patients. This indicates that these transfers were appropriate.
Signal transduction pathways activated by insulin‐like peptide 5 at the relaxin family peptide RXFP4 receptor
Authors: Ang Sheng Y , Hutchinson Dana S , Patil Nitin , Evans Bronwyn A , Bathgate Ross A D , Halls Michelle L , Hossain Mohammed A , Summers Roger J , Kocan Martina
Published: May 2016

Background and Purpose

Insulin‐like peptide 5 (INSL5) is a two‐chain, three‐disulfide‐bonded peptide of the insulin/relaxin superfamily, uniquely expressed in enteroendocrine L‐cells of the colon. It is the cognate ligand of relaxin family peptide RXFP4 receptor that is mainly expressed in the colorectum and enteric nervous system. This study identifies new signalling pathways activated by INSL5 acting on RXFP4 receptors.

Experimental Approach

INSL5/RXFP4 receptor signalling was investigated using AlphaScreen® proximity assays. Recruitment of Gαi/o proteins by RXFP4 receptors was determined by rescue of Pertussis toxin (PTX)‐inhibited cAMP and ERK1/2 responses following transient transfection of PTX‐insensitive Gαi/o C351I mutants. Cell proliferation was studied with bromodeoxyuridine. RXFP4 receptor interactions with β‐arrestins, GPCR kinase 2 (GRK2), KRas and Rab5a was assessed with real‐time BRET. Gene expression was investigated using real‐time quantitative PCR. Insulin release was measured using HTRF and intracellular Ca2+ flux monitored in a Flexstation® using Fluo‐4‐AM.

Key Results

INSL5 inhibited forskolin‐stimulated cAMP accumulation and increased phosphorylation of ERK1/2, p38MAPK, Akt Ser473, Akt Thr308 and S6 ribosomal protein. cAMP and ERK1/2 responses were abolished by PTX and rescued by mGαoA, mGαoB and mGαi2 and to a lesser extent mGαi1 and mGαi3. RXFP4 receptors interacted with GRK2 and β‐arrestins, moved towards Rab5a and away from KRas, indicating internalisation following receptor activation. INSL5 inhibited glucose‐stimulated insulin secretion and Ca2+ mobilisation in MIN6 insulinoma cells and forskolin‐stimulated cAMP accumulation in NCI‐H716 enteroendocrine cells.

Conclusions and Implications

Knowledge of signalling pathways activated by INSL5 at RXFP4 receptors is essential for understanding the biological roles of this novel gut hormone.

Linked Articles

This article is part of a themed section on Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.10/issuetoc
Sry‐like high‐mobility group box antibody‐related paraneoplastic cerebellar degeneration in the background of underlying non‐small cell lung cancer
Authors: Onder Halil , Kurtulan Olcay
Published: May 2016

Background

Paraneoplastic neurological syndromes (PNS) are defined as all non‐metastatic neurological complications of cancer in which no other etiologies, such as vascular, infectious or metabolic, were determined. Recently, Sry‐like high‐mobility group box (SOX1) antibody associated with PNS has been described, and is associated with Lambert–Eaton myasthenic syndrome, paraneoplastic cerebellar degeneration and paraneoplastic peripheral neuropathy invariably in the background of underlying small‐cell lung cancer.

Case presentation

A 75‐year‐old man was admitted to our neurology clinic at Hacettepe University Hospital, Sihhiye, Ankara, Turkey with complaints of imbalance and memory impairment that had started 2 months earlier and progressively increased. Neurological examination showed a state of delirium in the background of rapid progressive dementia and severely truncal ataxia. Cranial magnetic resonance imaging was unremarkable; however, in further investigations, thoracic tomography yielded bilateral hilar lymphadenopathy, and paraneoplastic antibody investigations resulted in positive SOX1 antibody. The following thoracic excisional lymph node biopsy investigations supported the diagnosis of non‐small‐cell lung cancer and paraneoplastic cerebellar degeneration associated with SOX1 antibody in the background of non‐small‐cell lung cancer. Adjuvant chemotherapy was started, but the patient deteriorated, which prevented proper plasmapheresis therapy. He died in the second month of admission as a result of severe sepsis leading to septic shock.

Conclusions

Here, we show the second case diagnosed with PNS in association with non‐small‐cell lung cancer. We note the importance of SOX1 antibody as a marker for PNS, and suggest that investigations of this antibody be carried out in larger case studies.
Patients’ perceptions of implant placement surgery, the post‐surgical healing and the transitional implant prostheses: a qualitative study
Authors: Kashbour Wafa A. , Rousseau Nikki , Thomason J. Mark , Ellis Janice S.
Published: May 2016

Objectives

This study aimed to explore patients’ thoughts, feelings about, and experiences of, implant placement surgery (IPS), the post‐surgical healing stage and the immediate post‐surgical transitional implant prosthesis (TIP) (fixed and removable).

Methods

A qualitative study design was chosen and 38 semi‐structured telephone and face‐to‐face interviews were conducted with 34 patients at different stages of implant treatment. The interviews were transcribed verbatim; the data collection and coding process followed the principles of thematic analysis, which was facilitated through the use of NVivo10.

Results

Patients anticipated that surgery would be painful and unpleasant but were prepared to accept this temporary discomfort for the expected benefits of implant treatment. However, a key finding was that patients felt they had overestimated the trauma of surgery but underestimated the discomfort and difficulties of the healing phase. A number of difficulties were also identified with the TIP phase following implant surgery.

Conclusion

Existing research has tended to focus on the longer term benefits of dental implant treatment. This qualitative study has investigated in‐depth patients’ perceptions of dental implant surgery, including their experiences related to sedation, and of transitional implant restoration. While patients felt their concerns were overestimated in relation to the implant surgery, they experienced greater morbidity than they expected in the healing phase. Recommendations are made for relatively small changes in care provision which might improve the overall patient experience. Partial dentate patients treated with a fixed transitional prosthesis experienced advantages more quickly than patients with an overdenture.
Obesity‐related health status is a better predictor of pregnancy with fertility treatment than body mass index: a prospective study
Authors: Paterson N. , Sharma A. M. , Maxwell C. , Greenblatt E. M.
Published: May 2016

This study assessed whether an obesity‐related health status instrument (Edmonton obesity scoring system – EOSS) or body mass index (BMI) better predicted pregnancy rates in overweight women undergoing fertility treatments. A prospective cohort study was conducted on patients with a BMI ≥ 25 kg m−2 undergoing a fertility treatment cycle (ovulation induction, superovulation, or in vitro fertilization). Obesity‐related health status including blood pressure, blood work, health history, and functional assessment were assessed. A total of 101 patients were included in the study with an average age of 36.3 ± 4.2 years and a mean BMI of 31.8 ± 5.2 kg m−2. EOSS was found to be statistically predictive of pregnancy rate/cycle (OR 0.51, 95% CI 0.27–0.94; P = 0.03), whereas BMI was not (OR 0.95, 95% CI 0.86–1.05). A similar trend was seen for clinical pregnancy rate/cycle started. However, the association between clinical pregnancy rates and EOSS or BMI did not reach statistical significance (OR 0.53, P = 0.06 and OR 0.98, P = 0.62 respectively). Our results demonstrated that EOSS better predicted pregnancy rates after fertility treatments than BMI. In fact, for every EOSS stage increased by one unit, the odds of pregnancy were approximately halved. A multi‐centre study powered for live birth is warranted to establish effective pre‐fertility management of overweight women.
A potential role for N‐acetylcysteine in the management of methamphetamine dependence
Authors: McKetin Rebecca , Dean Olivia M. , Baker Amanda L. , Carter Greg , Turner Alyna , Kelly Peter J. , Berk Michael
Published: May 2016

Methamphetamine dependence is a growing problem in Australia and globally. Currently, there are no approved pharmacotherapy options for the management of methamphetamine dependence. N‐acetylcysteine is one potential pharmacotherapy option. It has received growing attention as a therapy for managing addictions because of its capacity to restore homeostasis to brain glutamate systems disrupted in addiction and thereby reduce craving and the risk of relapse. N‐acetylcysteine also has antioxidant properties that protect against methamphetamine‐induced toxicity and it may therefore assist in the management of the neuropsychiatric and neurocognitive effects of methamphetamine. This commentary overviews the actions of N‐acetylcysteine and evidence for its efficacy in treating addiction with a particular focus on its potential utility for methamphetamine dependence. We conclude that the preliminary evidence indicates a need for full‐scale trials to definitively establish whether N‐acetylcysteine has a therapeutic benefit and the nature of this benefit, for managing methamphetamine dependence. [McKetin R, Dean O, Baker A. L, Carter G, Turner A, Kelly P. J, Berk M. A potential role for N‐acetylcysteine in the management of methamphetamine dependence. Drug Alcohol Rev 2017;36:153–159]
Perceived unmet need and barriers to care amongst street‐involved people who use illicit drugs
Authors: Hyshka Elaine , Anderson Jalene Tayler , Wild T. Cameron
Published: May 2016

Introduction and Aims

Research on perceived unmet need for care for mental health and substance use problems focuses on general populations to the detriment of hidden populations. This study describes prevalence and correlates of perceived unmet need for care in a community‐based sample of street‐involved people who use illicit drugs and identifies barriers to care.

Design and Methods

A sample of 320 street‐involved people who use drugs participated in a structured, interviewer‐assisted survey in Edmonton, Canada. The survey included the Perceived Need for Care Questionnaire, which assessed unmet need for care for mental health and substance use problems across seven service types. Logistic regression examined the associations between perceived unmet need, extent of socioeconomic marginalisation and problem severity. Barriers underlying unmet service needs were also examined.

Results

Most (82%) participants reported unmet need for one or more services during the past year. Odds of reporting one or more unmet needs were elevated amongst participants reporting substantial housing instability (adjusted odds ratio = 2.37; 95% confidence interval 1.19–4.28) and amongst participants meeting criteria for drug dependence (adjusted odds ratio = 1.22; 95% confidence interval 1.03–1.50), even after adjustment for sociodemographic covariates. Structural, rather than motivational barriers were the most commonly reported reasons underlying unmet service needs.

Discussion and Conclusion

Street‐involved people who use drugs experience very high rates of perceived unmet need for care for mental health and substance use problems. General population studies on perceived unmet need are insufficient for understanding needs and barriers to care in hidden populations.[Hyshka E, Anderson JT, Wild TC. Perceived unmet need and barriers to care amongst street‐involved people who use illicit drugs. Drug Alcohol Rev 2017;36:295–304]
Six1 is required for mouse dental follicle cell and human periodontal ligament‐derived cell proliferation
Authors: Kawasaki Tatsuki , Takahashi Masanori , Yajima Hiroshi , Mori Yoshiyuki , Kawakami Kiyoshi
Published: May 2016

The periodontal ligament (PDL) is a connective tissue that attaches the tooth cementum to the alveolar bone and is derived from dental follicle cells (DFCs). The DFCs form fibroblasts, osteoblasts, cementoblasts, and PDL stem cells (PDLSCs). We previously reported homeobox transcription factor Six1 expression in mouse DFCs. However, the role of Six1 in periodontal tissue development is largely unknown. In this study, we analyzed SIX1 expression in mouse periodontal tissue cells during postnatal development and adulthood. We also addressed the role of SIX1 in mouse periodontium development and in human cultured PDL‐derived cells (PDLCs). In mouse development, SIX1 production was abundant in DFCs and PDL cells by 2 weeks, but it was greatly diminished in the PDL at 4 weeks and in adults. Although the SIX1‐positive cell distribution was sparse in the adult PDL, SIX1‐positive cells were observed with low expression levels. We used 5‐ethynyl‐2′‐deoxyuridine (EdU) for cell labeling to reveal numerous EdU/SIX1‐double positive cells at 2 weeks; however, a few EdU‐positive cells remained at 4 weeks. The proportion of DFCs that incorporated EdU was significantly lower in Six1‐deficient mice compared with wild‐type mice at E18.5. In human PDLCs, SIX1 was intensely expressed, and SIX1‐knockdown using siRNA reduced proliferating PDLCs. Our results suggest that SIX1 is a key proliferation regulator in mouse DFCs and human PDLCs, which provides novel insight into Six family gene function in mammals.
Incidence of crown fracture and risk factors in the primary dentition: a prospective longitudinal study
Authors: Corrêa‐Faria Patrícia , Paiva Saul Martins , Ramos‐Jorge Maria Letícia , Pordeus Isabela Almeida
Published: May 2016

Background/Aim

Few studies have assessed the incidence and risk factors to crown fractures in preschool children. The aim of this study was to estimate the incidence of crown fracture in the primary dentition over a 1‐year follow‐up period, identify risk factors, and test the hypothesis that children with previous crown fracture are more prone to experience further cases of crown fracture independently of other risk factors.

Materials and Methods

This study was developed in two phases: cross‐sectional and prospective longitudinal study. The cross‐sectional study was carried out 261 preschool children. The prospective longitudinal study was carried out 194 children allocated to two groups: exposed group (children with prior exposure to crown fracture) and non‐exposed group (children without prior exposure). On both occasions, children were examined for the diagnosis of crown fracture and evaluation of lip coverage and overjet. The parents were interviewed with regard to the socioeconomic indicators. New cases of crown fracture were identified based on the comparison of the two examinations. Data analysis involved Pearson's chi‐square test, McNemar's test, and Poisson regression with robust variance.

Results

Among the 261 children who participated in the cross‐sectional study, 194 were re‐examined (65 in the exposed group and 129 in the non‐exposed group). The overall incidence of crown fracture was 55.7% (n = 108). The difference in percentage of increased risk of crown fracture in exposed and non‐exposed groups was 13.4%. A greater incidence of crown fracture was found in the exposed group (64.6%; P < 0,001). The children exposed (RR: 1.30; 95% CI: 1.01–1.67) had a greater risk of developing new cases of crown fracture in comparison with the non‐exposed group.

Conclusion

The incidence of crown fracture was high and children with previous crown fracture had a greater risk of suffering new cases of crown fracture during the 1‐year follow‐up period.
When the State Becomes Part of the Exploitation: Migrants’ Agency within the Institutional Constraints in Australia
Authors: Li Yao‐Tai , Whitworth Katherine
Published: May 2016

Studies have shown the unequal treatments temporary migrants face in the processes of immigration. In Australia for a short period of time and not citizens, they face conditions that allow for employer exploitation. This article is interested in exploring how institutional structures shape and normalize the choices that migrants make to work in the cash economy or other exploitative conditions. To do this, we take PRC‐Chinese, Taiwanese, and Hong Kongese temporary migrants who hold either a student or Working Holiday visa in Australia as an example. Focusing on the policymaking process, we argue that the policy outcomes produced by visa restrictions placed on international students and Working Holiday Makers sometimes do not reach an ideal outcome and at times even exacerbate problems identified in the input stage of the policy process. Such institutional effects result in a more vulnerable and exploitable situation for temporary migrants in Australia's labour market.
Development of research discourses: a conceptual map
Authors: Freshwater Dawn , Cahill Jane
Published: May 2016

Aim

The aim of this study was to discuss: (1) how methodologies are constructed and perpetuated in the context of research paradigms; (2) what exactly constitutes a paradigm; (3) how the proposed conceptual map of discourse development provides a new and original method for understanding knowledge production.

Background

In nursing research, methodologies are constructed by several external and internal contextually driven influences. Our focus is on how two methodological paradigms – evidence‐based practice and mixed methods – continue to impact and be impacted by patterns of knowledge production.

Design

Discussion paper.

Data sources

This discussion is based on our own experiences and supported by literature and theory using examples from the two paradigms to illustrate how discourses are developed, perpetuated and deconstructed and how these have specific impacts on qualitative nursing research.

Implications for nursing

The conceptual map should be used to cultivate an awareness in practitioners, researchers and policy makers of how discourses surrounding research evidence and research practices are generated. This level of awareness will facilitate critical reflection on how certain practices assume dominance, potentially leading to hegemony in nursing research, practice and scholarship.

Conclusion

This research offers a critical examination of the meaning of paradigms and a meta‐perspective on the production and practice of methodologies using a conceptual map of discourse development as a heuristic device. We anticipate that these examples will encourage debate and discussion on how methodologies and paradigms are perpetuated in academia and the impact this has on nursing knowledge.
Supplier Role Conflict: An Investigation of Its Relational Implications and Impact on Supplier Accommodation
Authors: Murfield Monique L. Ueltschy , Esper Terry L. , Tate Wendy L. , Petersen Kenneth J.
Published: May 2016

Existing research on supply chain relationships suggests that one of the underlying tensions between supply chain partners is that of opposing perspectives and goals in the customer−supplier relationship. In today's business world with requirements in constant flux, suppliers are often asked to accommodate “special” requests made by their customers, not part of the contractual agreement. Suppliers frequently fill requests to protect the relationship with the customer, even if they fall outside of what they consider their role as a supplier. Issues of supplier role conflict emerge when customers and suppliers have different views of what the supplier's role should entail. There is little research examining the potential for supplier role conflict in supply chains. Specifically, this research draws on literature from multiple disciplines to consider supplier role conflict that may stem from accommodation and the impact of this role conflict and supplier accommodation on the supply chain relationship and future accommodation behavior. Hypotheses are tested using two scenario‐based experiments. Results suggest that supplier adaptation and flexibility both have positive relational effects. If suppliers perceive accommodation requests as outside of their contracted role, supplier role conflict can have detrimental effects on the supplier's relationship perceptions and their willingness for future accommodation.
Tracing Bad Products in Supply Chains: The Roles of Temporality, Supply Chain Permeation, and Product Information Ambiguity
Authors: Wowak Kaitlin D. , Craighead Christopher W. , Ketchen David J.
Published: May 2016

To minimize negative consequences, bad products must be removed quickly once found within supply chains. This makes traceability—the ability to track the flow of a product—a key issue. Unfortunately, firms struggle to create traceability and little interdisciplinary research has been conducted in this area. Accordingly, we conducted a grounded theory investigation that transcends functional and organizational boundaries. Although past literature tends to consider a firm's ability to trace products as one‐dimensional and inherently good or bad, we find that a firm's ability to trace products varies based on contextual factors. Specifically, our study reveals that traceability is hindered by temporality (i.e., time pressures that strain a firm's ability to track products), supply chain permeation (i.e., supply chain flow characteristics that represent the degree of bad product infiltration), and product information ambiguity (i.e., product characteristics that create vagueness about what to trace). We provide prescriptive advice about how firms can overcome these traceability barriers and thus enhance their ability to identify and recall tainted products. Broadly, our findings support the need to manage traceability from a nuanced approach and to seek boundary‐spanning supply chain solutions.
The Coevolution of Relationship Dominant Logic and Supply Risk Mitigation Strategies
Authors: Kaufmann Lutz , Carter Craig R. , Rauer Johan
Published: May 2016

How and why do risk mitigation strategies evolve? And which resources are needed for engaging in such changes? This paper contributes to the understanding of risk management in supply chains by developing theory about the interplay between supply risk mitigation strategies and the purchasing team's relationship dominant logic (RDL), which we define as the purchasing team's orientation toward and shared cognitive map of the management of its supply chain relationships. Specifically, we propose that RDL and supply risk mitigation strategies are fundamentally intertwined. Following a Straussian approach to grounded theory, this study analyzes data generated from the purchasing teams of Western green‐tech firms trying to mitigate supply risk for technically indispensable rare earth metals from China. Our findings from this context that is heavily shaped by state‐influenced supply chain members show that the firms chose their mitigation strategies in line with their RDL. Human capital, social capital, and financial capital seem to moderate the link between RDL and mitigation strategies. We link our findings with the strategic management literature in deriving theoretical propositions concerning these relationships.
How Transdisciplinarity Can Help to Improve Operations Research on Sustainable Supply Chains—A Transdisciplinary Modeling Framework
Authors: Stindt Dennis , Sahamie Ramin , Nuss Christian , Tuma Axel
Published: May 2016

We present a transdisciplinary modeling framework that enhances collaborative research on sustainable supply chain management (SSCM). Decision support concerning such systems is commonly provided using operations research (OR) methodologies. The quality of respective models depends on the appropriateness of both mathematical representation of the focal system and data input. Concerning this matter, OR faces severe criticism as groundwork is commonly neglected. This results in a lack of holistic understanding and in insufficient modeling of real‐world problems. Crucial characteristics of the underlying system are often over simplified due to single‐discipline assessments. Particularly, in the context of complex sustainability challenges, multiple nonacademic competencies and expertise are required. Although latest research indicates that collaborative research settings are highly beneficial regarding SSCM, a dearth of integration between disciplines exists. Therefore, we develop a conceptual framework that helps to overcome these shortcomings based on the paradigm of transdisciplinary research (TDR), which needs substantiation to enhance collaboration and to ensure applicability. Accordingly, we propose appropriate methodologies for each step within the framework. Overall, the framework enables holistic analysis of a focal system by providing a sound approach for SSCM‐oriented TDR projects. The value of the framework is eventually demonstrated by two cases that deal with SSCM issues.
MiR‐16 regulates mouse peritoneal macrophage polarization and affects T‐cell activation
Authors: Jia Xiaoqin , Li Xiaomin , Shen Yating , Miao Junjun , Liu Hao , Li Guoli , Wang Zhengbing
Published: May 2016

MiR‐16 is a tumour suppressor that is down‐regulated in certain human cancers. However, little is known on its activity in other cell types. In this study, we examined the biological significance and underlying mechanisms of miR‐16 on macrophage polarization and subsequent T‐cell activation. Mouse peritoneal macrophages were isolated and induced to undergo either M1 polarization with 100 ng/ml of interferon‐γ and 20 ng/ml of lipopolysaccharide, or M2 polarization with 20 ng/ml of interleukin (IL)‐4. The identity of polarized macrophages was determined by profiling cell‐surface markers by flow cytometry and cytokine production by ELISA. Macrophages were infected with lentivirus‐expressing miR‐16 to assess the effects of miR‐16. Effects on macrophage–T cell interactions were analysed by co‐culturing purified CD4+ T cells with miR‐16‐expressing peritoneal macrophages, and measuring activation marker CD69 by flow cytometry and cytokine secretion by ELISA. Bioinformatics analysis was applied to search for potential miR‐16 targets and understand its underlying mechanisms. MiR‐16‐induced M1 differentiation of mouse peritoneal macrophages from either the basal M0‐ or M2‐polarized state is indicated by the significant up‐regulation of M1 marker CD16/32, repression of M2 marker CD206 and Dectin‐1, and increased secretion of M1 cytokine IL‐12 and nitric oxide. Consistently, miR‐16‐expressing macrophages stimulate the activation of purified CD4+ T cells. Mechanistically, miR‐16 significantly down‐regulates the expression of PD‐L1, a critical immune suppressor that controls macrophage–T cell interaction and T‐cell activation. MiR‐16 plays an important role in shifting macrophage polarization from M2 to M1 status, and functionally activating CD4+ T cells. This effect is potentially mediated through the down‐regulation of immune suppressor PD‐L1.
What is the biological reality of gene–environment interaction estimates? An assessment of bias in developmental models
Authors: Moore Sarah R. , Thoemmes Felix
Published: May 2016

Background

Standard models used to test gene–environment interaction (G × E) hypotheses make the causal assumption that there are no unobserved variables that could be biasing the interaction estimate. Whether this assumption can be met in nonexperimental studies is unclear because the interactive biological pathways from genetic polymorphisms and environments to behavior, and the confounders that can be introduced along these pathways, are often not delineated. This is problematic in the context of studies focused on caregiver–child dyads, in which common genes and environments induce gene–environment correlation. To address the impact of sources of bias in G × E models specifically assessing the interaction between child genotype and caregiver behavior, we provide a causal framework that integrates biological and statistical concepts of G × E, and assess the magnitude of bias introduced by various confounding pathways in different causal circumstances.

Methods

A simulation assessed the magnitude of bias introduced by four types of confounding pathways in different causal models. Unadjusted and adjusted statistical models were then applied to the simulated data to assess the efficacy of these procedures to capture unbiased G × E estimates. Finally, the simulation was run under null effects of the genotype to assess the impact of biasing sources on the false‐positive rate.

Results

Common environmental pathways between caregiver and child inflated G × E estimates and raised the false‐positive rate. Evocative effects of the child also inflated G × E estimates.

Conclusions

Gene–environment interaction studies should be approached with consideration to the causal pathways at play and the confounding opportunities along these pathways to facilitate the inclusion of adequate statistical controls and correct inferences from study findings. Bridging biological and statistical concepts of G × E can significantly improve research design and the communication of how a G × E process fits into a broader developmental framework.
Using machine learning to model dose–response relationships
Authors: Linden Ariel , Yarnold Paul R , Nallamothu Brahmajee K
Published: May 2016

Rationale, aims and objectives

Establishing the relationship between various doses of an exposure and a response variable is integral to many studies in health care. Linear parametric models, widely used for estimating dose–response relationships, have several limitations. This paper employs the optimal discriminant analysis (ODA) machine‐learning algorithm to determine the degree to which exposure dose can be distinguished based on the distribution of the response variable. By framing the dose–response relationship as a classification problem, machine learning can provide the same functionality as conventional models, but can additionally make individual‐level predictions, which may be helpful in practical applications like establishing responsiveness to prescribed drug regimens.

Method

Using data from a study measuring the responses of blood flow in the forearm to the intra‐arterial administration of isoproterenol (separately for 9 black and 13 white men, and pooled), we compare the results estimated from a generalized estimating equations (GEE) model with those estimated using ODA.

Results

Generalized estimating equations and ODA both identified many statistically significant dose–response relationships, separately by race and for pooled data. Post hoc comparisons between doses indicated ODA (based on exact P values) was consistently more conservative than GEE (based on estimated P values). Compared with ODA, GEE produced twice as many instances of paradoxical confounding (findings from analysis of pooled data that are inconsistent with findings from analyses stratified by race).

Conclusions

Given its unique advantages and greater analytic flexibility, maximum‐accuracy machine‐learning methods like ODA should be considered as the primary analytic approach in dose–response applications.
Invasion status of the common carp Cyprinus carpio in inland waters of Argentina
Authors: Maiztegui T. , Baigún C. R. M. , Garcia de Souza J. R. , Minotti P. , Colautti D. C.
Published: May 2016

This study documents the presence of Cyprinus carpio in 119 natural environments and 49 artificial habitats in Argentina, showing an exponential increment of invaded locations over time since it was introduced in the nineteenth century. Geographic expansion patterns revealed that since its initial introduction, species records demonstrate an increment in the central portion of the country only after 1970 and subsequent expansion after 1990 to the north, west and south. Using an environmental similarity index it was determined that more than half the country offers good conditions for C. carpio establishment. Environmental factors and anthropogenic impacts are relevant drivers that can account for the current and future distribution of C. carpio in Argentina.
Mercury and methyl mercury in fishes from Bacajá River (Brazilian Amazon): evidence for bioaccumulation and biomagnification
Authors: Souza‐Araujo J. , Giarrizzo T. , Lima M. O. , Souza M. B. G.
Published: May 2016

This study assessed total mercury (THg) and methyl mercury (MeHg) concentrations, bioaccumulation and biomagnification of THg through the food web in fishes consumed by indigenous communities of Bacajá River, the largest tributary of the right bank of Xingu River. In total, 496 fish (22 species) were sampled. Nine species had THg concentrations above the limit recommended by the World Health Organisation (0·5 µg g−1 wet mass), and one exceeded the recommended level for Hg in predatory fishes by Brazilian law (1·0 µg g−1). The average concentration of THg increased significantly with trophic guild (herbivorous to piscivorous) and trophic level, with higher accumulation in fishes with greater total length. Ninety‐six per cent of all mercury was methylated. These results suggest that feeding habits determine THg concentrations in fishes and that Hg elimination rate is slow during growth, which allows greater accumulation. These findings show that fishes in the Bacajá River contain high concentrations of THg and MeHg.
Projected Savings and Workforce Transformation from Converting Independence at Home to a Medicare Benefit
Authors: Kinosian Bruce , Taler George , Boling Peter , Gilden Dan ,   the Independence at Home Learning Collaborative Writing Group
Published: May 2016

The Independence at Home (IAH) Demonstration Year 1 results have confirmed earlier studies that showed the ability of home‐based primary care (HBPC) to improve care and lower costs for Medicare's frailest beneficiaries. The first‐year report showed IAH savings of 7.7% for all programs and 17% for the nine of 17 programs that surpassed the 5% mandatory savings threshold. Using these results as applied to the Medicare 5% claims file, the effect of expanding HBPC to the 2.2 million Medicare beneficiaries who are similar to IAH demonstration participants was projected. Total savings ranged from $12 billion to $53 billion depending on the speed and extent of dissemination of HBPC among this IAH‐like population. Using a fixed growth rate, as hospitalists experienced in their first decade, 35% coverage would be achieved at the end of 10 years, with total 10‐year savings through IAH reaching $37.5 billion and $17.3 billion accruing to the Centers for Medicare and Medicaid Services as a net reduction in overall expenditures, with $12.6 billion from Medicare Parts A and B savings.
An Urban Metabolism and Carbon Footprint Analysis of the Jing–Jin–Ji Regional Agglomeration
Authors: Zheng Hongmei , Fath Brian D. , Zhang Yan
Published: May 2016

Urban energy metabolism includes processes for exploiting, transforming, and consuming energy, as well as processes for recycling by‐products and wastes. Embodied energy is the energy consumed during all of these activities, both directly and indirectly. Multiregional input‐output (MRIO) analysis can calculate the energy consumption embodied in flows among sectors for multiple cities or regions. Our goal was to address a problem apparent in previous research, which was insufficient attention to indirect energy flows. We combined MRIO analysis with ecological network analysis to calculate the embodied energy consumption and the energy‐related carbon footprints of five sectors in three regions that comprise the Jing‐Jin‐Ji agglomeration, using data from 2002 and 2007. Our analysis traced metabolic processes of sectors from the perspective of final consumption. Based on the embodied energy analysis, we quantified the indirect energy consumption implied in exchanges of sectors and its distribution and identified the relationships formed through the indirect consumption to analyze the roles of providers and receivers in the system. Results showed that the embodied energy consumption for the Jing‐Jin‐Ji region increased from 2002 to 2007 as a result of increased energy consumption in Tianjin and Hebei. Overall, consumption of Beijing decreased likely attributable to the fact that government policies relocated industries during this time in anticipation of the Olympic Games. The relationships among sectors changed: Beijing changed from a net exporter to an importer, whereas Hebei changed from a net importer of energy from Beijing to an exporter to Beijing, and Tianjin served as an importer in both years.
Intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyradiculoneuropathy, a time to start and a time to stop
Authors: Adrichem Max E. , Eftimov Filip , van Schaik Ivo N.
Published: May 2016

Intravenous immunoglobulin (IVIg) is often used as preferred treatment in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Several studies highlighted the short‐term efficacy of IVIg for CIDP yet many patients need maintenance therapy. Notwithstanding the fact IVIg has been used for over 30 years in CIDP, there is only limited evidence to guide dosage and interval during maintenance treatment. The variation in disease course, lack of biomarkers, and fear of deterioration after stopping IVIg makes long‐term treatment challenging. Recent studies suggest a proportion of patients receive unnecessary IVIg maintenance treatment. This review provides an overview of the use of IVIg for CIDP treatment, focusing on evidence for long‐term IVIg use.
A lesbian, gay, bisexual and transgender dedicated inpatient psychiatric unit in rural New England: a descriptive analysis in demographics, service utilisation and needs
Authors: Klotzbaugh Ralph , Glover Eileen
Published: May 2016

Aims and objectives

To develop an understanding of lesbian‐, gay‐, bisexual‐, transgender‐specific mental health and substance abuse needs in rural populations and to improve data about sexual orientation and gender identity.

Background

Existing literature on mental health needs for lesbian, gay, bisexual and transgender populations has continued to reveal higher levels of need. Research has also demonstrated that few mental health providers have expertise or comfort in treating lesbian, gay, bisexual and transgender clients.

Design

Descriptive correlational study.

Methods

A sample (n = 456) of patient records admitted to a rural lesbian, gay, bisexual and transgender inpatient psychiatric clinic over 12 months were examined using descriptive statistics. Patient zip code information was used to determine the levels of rurality. Chi‐square analysis was used to determine relationships between sexual orientation, rural/urban distinctions and concomitant drug use.

Results

Unexpectedly, those who identified as heterosexual were significantly more likely to concomitantly abuse alcohol and heroin than those who identified as lesbian, gay, bisexual and transgender. Patients residing in small or isolated rural areas were more likely to abuse alcohol or synthetics than those residing in urban or micropolitan areas.

Conclusions

Results of this study concerning substance abuse among lesbian, gay, bisexual and transgender individuals are not reflective of prior studies. LGBT patients did not demonstrate a higher proportion of substance abuse compared with those identifying as heterosexual. Increased substance abuse among those from rural isolated areas does support prior studies. The context of gathering demographic information on sexual orientation was thought by staff to increase the number of those identifying as heterosexual.

Relevance to clinical practice

Context in which sensitive questions are asked may affect the accuracy of demographic data. Lack of information regarding patients’ sexual orientation or gender identity may impact perceived need for culturally competent care. Results suggest the need for efforts to provide training for mental health specialists in rural areas to provide sensitive care.
Optimized Implantation Height of the Edwards SAPIEN 3 Valve to Minimize Pacemaker Implantation After TAVI
Authors: Schwerg Marius , Fulde Felix , Dreger Henryk , Poller Wolfram C. , Stangl Karl , Laule Michael
Published: May 2016

Aim

The transcatheter aortic valve SAPIEN 3 aims at reducing paravalvular leakage (PVL). The new design with outer sealing cuff may increase the risk of permanent pacemaker implantation (PPM). The aim of our study was to evaluate the optimal implantation height of the SAPIEN 3.

Methods and Results

We analysed the correlation between the implantation height of the valve and the need for PPM in 131 patients. The PPM rate for the entire group after TAVI was 18% (n = 24). In patients with a marker distance <2 mm (“low implantation”), the PPM rate was 32%, whereas in patients with a distance ≥2 mm (“high implantation”), the rate was only 4.7% (OR of 0.1 (0.03–0.37, P < 0.001)).

Conclusion

The risk of periprocedural PPM with the Edwards SAPIEN 3 depends on implantation height; it is increased when using conventional implantation techniques. This risk can be minimized below 5% PPM by choosing a higher implantation technique with the central marker 2 mm or more over the annulus plane.
Surface Microstructural Changes and Release of Ions from Dental Metal Alloy Removable Prostheses in Patients Suffering from Acid Reflux
Authors: Borg William , Cassar Glenn , Camilleri Liberato , Attard Nikolai , Camilleri Josette
Published: May 2016

Purpose

To investigate the surface microstructural changes and the release of ions from metal alloys used in removable dental prostheses and the potential effects of acidic reflux found in patients suffering from gastroesophageal reflux disease (GERD).

Materials and Methods

Thirty‐seven (37) patients were recruited. Data were gathered through a questionnaire and clinical examination. Samples of metal alloy from the dentures and patient's saliva were collected. GERD was confirmed using the GerdQ questionnaire. Denture samples were characterized using scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS), while salivary samples were tested for trace metal ions using inductively coupled plasma (ICP).

Results

Characterization of denture samples revealed the presence of nickel, cobalt, and chromium. Nickel‐chromium exhibited an etched surface appearance, while cobalt‐chromium exhibited no noticeable surface microstructural changes. Higher mean salivary levels of chromium and cobalt in patients wearing any metal alloy‐based denture and of chromium and nickel in patients wearing Ni‐Cr prostheses were found to be significant. No differences were found in salivary metal ion levels of patients suffering from GERD.

Conclusions

Nickel‐chromium alloy is prone to acid etching in the oral cavity, while cobalt‐chromium alloy appears to be more resistant. Cobalt, chromium, and nickel are leached in saliva of patients using cast removable prostheses. The impact of gastric acid on metal ion release from dental metal alloys deserves further investigations.

Clinical Significance

This preliminary study suggests that metal‐based removable prostheses leach trace metal ions in saliva. Nickel‐chromium‐based dentures exhibit an etched appearance unrelated to GERD.
A longitudinal study assessing childcare services' adoption of obesity prevention policies and practices
Authors: Yoong Sze Lin , Finch Meghan , Nathan Nicole , Wiggers John , Lecathelinais Christophe , Jones Jannah , Dodds Pennie , Wolfenden Luke
Published: May 2016

Aim

Despite ongoing investments to improve the obesogenic environments of childcare settings, little is known regarding how these services have changed their physical activity and nutrition‐promoting practices. This study aims to describe changes in the proportion of Australian childcare services that have adopted best‐practice healthy eating and physical activity practices between 2006 and 2013 and to assess whether adoption varied by socio‐economic status and locality.

Methods

A randomly selected sample of nominated supervisors (n = 358) from childcare services located in New South Wales, Australia, participated in a telephone survey in 2006, 2009, 2010 and 2013. Supervisors reported on their service's adoption of six practices: (i) having written nutrition and physical activity policies; (ii) staff trained in physical activity and nutrition in the past year; (iii) scheduled time for fundamental movement skills and (iv) outdoor play; (v) weekly or less screen time opportunities; and (vi) serving only non‐sweetened beverages.

Results

A significant increase in the prevalence of services adopting all but one practice, between 2006 and 2013 was identified. Ninety one percent of services adopted four or more practices, a significant increase from 38% in 2006. There were no differences in the proportion of services adopting each practice by locality and socio‐economic status.

Conclusions

Government investment in obesity prevention programmes can equitably improve childcare service's adoption of healthy eating and physical activity promoting practices on a jurisdiction‐wide basis. The establishment of a routine system to monitor adoption of a broader range of practices by childcare services is warranted.