bluuebunny/crossref_metadata_2025 huggingface dataset:
Inverse correlation of expression of microRNA‐140‐5p with progression of multiple sclerosis and differentiation of encephalitogenic T helper type 1 cells
Authors: Guan Hongbing , Singh Udai P. , Rao Roshni , Mrelashvili Davit , Sen Souvik , Hao Haiping , Zumbrun Elizabeth E. , Singh Narendra P. , Nagarkatti Prakash S. , Nagarkatti Mitzi
Published: January 2016

The role of microRNA in the regulation of encephalitogenic T‐cell development is of interest in understanding the pathogenesis of multiple sclerosis (MS). Direct binding of microRNAs to their target mRNAs usually suppresses gene expression and facilitates mRNA degradation. In this study, we observed that the expression of several microRNAs was significantly altered in patients with MS. Interestingly, the expression of miR‐140‐5p, among other microRNAs, was significantly decreased in the peripheral blood mononuclear cells of patients with MS, and this microRNA may regulate encephalitogenic T helper type 1 (Th1) cell differentiation. The expression level of miR‐140‐5p was inversely correlated with disease severity with greater reduction in relapsing disease compared with remitting disease. Transfection of synthetic miR‐140‐5p in peripheral blood mononuclear cells suppressed encephalitogenic Th1 differentiation. Signal transducer and activator of transcription 1 (STAT1) was the functional target of miR‐140‐5p – transfection of the synthetic miR‐140‐5p suppressed activation of STAT1 and the expression of its downstream target, T‐bet. Our results suggested that miR‐140‐5p is probably involved in the regulation of encephalitogenic T cells in the pathogenesis of MS.
On the generalized bin packing problem
Authors: Baldi Mauro Maria , Bruglieri Maurizio
Published: January 2016

The generalized bin packing problem (GBPP) is a novel packing problem arising in many transportation and logistic settings, characterized by multiple items and bins attributes and the presence of both compulsory and non‐compulsory items. In this paper, we study the computational complexity and the approximability of the GBPP. We prove that the GBPP cannot be approximated by any constant, unless . We also study the particular case of a single bin type and show that when an unlimited number of bins is available, the GBPP can be reduced to the bin packing with rejection (BPR) problem, which is approximable. We also prove that the GBPP satisfies Bellman's optimality principle and, exploiting this result, we develop a dynamic programming solution approach. Finally, we study the behavior of standard and widespread heuristics such as the first fit, best fit, first fit decreasing, and best fit decreasing. We show that while they successfully approximate previous versions of bin packing problems, they fail to approximate the GBPP.
New Insight on Sintering Progress of KNN‐Based Lead‐Free Ceramics
Authors: Zhang Yang , Shen Bo , Zhai Jiwei , Zeng Huarong
Published: January 2016

0.96(K0.5Na0.5)0.95Li0.05Nb0.93Sb0.07O3–0.04CaZrO3 (0.96KNLNS–0.04CZ) lead‐free piezoelectric ceramics have been prepared by a new ceramics sintering progress—three‐step sintering method, via adjusting every step sintering temperature and holding time to improve piezoelectric properties. The result shows that the phase structure of the ceramics was changed from single phase to two phase coexisted by three‐step sintering, meanwhile, orthorhombic–tetragonal phase transition temperature was modified to around zero degree. Remarkably, piezoelectric properties has been obtained in 0.96KNLNS‐0.04CZ ceramics, which piezoelectric parameter is d33 =420 pC/N, Kp =0.485.
The juxtaposition of ageing and nursing: the challenges and enablers of continuing to work in the latter stages of a nursing career
Authors: Clendon Jill , Walker Léonie
Published: January 2016

Aims

To identify why some nurses cope well with continuing to work as they age and others struggle.

Background

There is a need to understand better the challenges older nurses face and how they manage them.

Design

Secondary analysis of existing data.

Methods

Data collected in two separate studies were analysed. The first study (2012) was an online, anonymous survey that collected free text (qualitative) and categorical data (n = 3273, 57·6% response rate). The second (2014) was an explorative, descriptive study that collected data through focus groups and interviews (n = 46). Qualitative data from both studies were analysed using David Thomas' () general inductive approach. Research Ethics Committee approval was gained for the 2012 and 2014 studies.

Results

Data were categorised in two themes: the challenges of ageing and nursing; and factors that enable nurses to continue to practice. Physical challenges, fatigue, guilt, ageism and demands to complete continuing education were considered challenges. Maintaining personal fitness, self care, flexible working and a strong belief in their ability to contribute to the profession were present in older nurses who continued to practice.

Conclusion

While older nurses face growing physical and cognitive challenges as they age, they demonstrate strong resilience in the face of these challenges. It is recommended nurses seek support from their workplaces early to address challenges. Organisations must address ageism in the workplace and provide practical interventions such as supporting changes to work hours, shifting nurses to less physical roles and providing career planning to support resilience in older workers.
Pitavastatin improves glycated hemoglobin in patients with poorly controlled type 2 diabetes
Authors: Huang Chung‐Huei , Huang Yu‐Yao , Hsu Brend Ray‐Sea
Published: January 2016

Aims/Introduction

To investigate the effect of pitavastatin on glucose control in patients with type 2 diabetes.

Materials and Methods

Medical records of 340 patients with type 2 diabetes treated with pitavastatin or atorvastatin between 1 August 2013 and 31 May 2014 were reviewed. A total of 96 patients who had not received statins were treated with pitavastatin (N to P group). A total of 100 patients who had previously used atorvastatin were switched to pitavastatin (A to P group). A total of 144 patients continued with atorvastatin treatment. Data were collected at baseline, 3 and 6 months of treatment. Changes in glycated hemoglobin (HbA1c) level were analyzed in 222 patients who did not change their antidiabetic agent during 6 months of treatment.

Results

A negative correlation between baseline HbA1c and delta HbA1c at 6 months was found in the pitavastatin‐treated patients (N to P group: ρ = −0.329, P = 0.006; A to P group: ρ = −0.480, P < 0.001). The correlation remained similar after adjusting for age, body mass index, dose of pitavastatin, estimated glomerular filtration rate and high‐density lipoprotein cholesterol. After 6 months of treatment, the benefit of pitavastatin on HbA1c in the patients with poorly controlled diabetes was significant in both the N to P (8.1 vs 7.4%, P = 0.018) and A to P (9.7 vs 9.0%, P = 0.015) groups.

Conclusions

Pitavastatin decreases HbA1c in patients with type 2 diabetes with a higher baseline HbA1c level. The benefit on HbA1c was also observed in patients with previous use of atorvastatin.
Parental and hybridDaphniafrom theD. longispinacomplex: long‐term dynamics in genetic structure and significance of overwintering modes
Authors: Griebel J. , Gießler S. , Yin M. , Wolinska J.
Published: January 2016

In recent decades, hybridization has become a focus of attention because of its role in evolutionary processes. However, little is known about changes in genetic structure within and between parental species and hybrids over time. Here, we studied processes of genetic change in parental species and hybrids from theDaphnia longispinacomplex (Crustacea, Cladocera) over a period of six years across ten habitats. These cyclical parthenogens respond to fluctuating environments by switching from asexual to sexual reproduction. Importantly, sexually produced diapausing eggs, which resist extreme conditions such as low temperatures and serve as dispersal stages, are produced to a lower extent by hybrids. Long‐term microsatellite data revealed clear differences between hybrids and parental species. In hybrids, clonal diversity values were lower, whereas heterozygosity and linkage disequilibrium values were higher compared to parental species. Clonal diversity of hybrids responded to the strength of the winter, with cold winters resulting in few genotypes in the following spring. In time windows when only asexual hybrid females survive, priority effects will favour the establishment of the hybrid offspring before hatchlings from parental diapause eggs can enter the community. The constant high levels of heterozygosity maintained by clonal reproduction in hybrids might lead to their successful establishment over time, when they are able to escape competition from both parental species. Although we found evidence that hybrids diversity depends on fluctuating environments, a direct link between hybrid abundance and the strength of winter was missing. Because of reduced adaptability in clonally reproducing hybrids, multiple factors must contribute to promoting their long‐term success in fluctuating environments.
Beyond the wing planform: morphological differentiation between migratory and nonmigratory dragonfly species
Authors: Suárez‐Tovar C. M. , Sarmiento C. E.
Published: January 2016

Migration is a significant trait of the animal kingdom that can impose a strong selective pressure on several structures to overcome the amount of energy that the organism invests in this particular behaviour. Wing linear dimensions and planform have been a traditional focus in the study of flying migratory species; however, other traits could also influence aerodynamic performance. We studied the differences in several flight‐related traits of migratory and nonmigratoryLibellulid species in a phylogenetic context to assess their response to migratory behaviour. Wings were compared by linear measurements, shape, surface corrugations and microtrichia number. Thorax size and pilosity were also compared. Migratory species have larger and smoother wings, a larger anal lobe that is reached through an expansion of the discoidal region, and longer and denser thoracic pilosity. These differences might favour gliding as an energy‐saving displacement strategy. Most of the changes were identified in the hind wings. No differences were observed for the thorax linear dimensions, wetted aspect ratio, some wing corrugations or the wing microtrichiae number. Similar changes in the hind wing are present in clades where migration evolved. Our results emphasize that adaptations to migration through flight may extend to characteristics beyond the wing planform and that some wing characteristics in libellulids converge in response to migratory habits, whereas other closely related structures remain virtually unchanged. Additionally, we concluded that despite a close functional association and similar selective pressures on a structure, significant differences in the magnitude of the response may be present in its components.
Simeprevir plus peginterferon/ribavirin for HCV genotype 1‐infected treatment‐naïve patients in China and South Korea
Authors: Wei Lai , Han Tao , Yang Dongliang , Heo Jeong , Shang Jia , Cheng Jun , Chen Xinyue , Xie Qing , Kim Ju‐Hyun , Kalmeijer Ronald , Ouwerkerk‐Mahadevan Sivi , Hoeben Eva , Lenz Oliver , Verbinnen Thierry , Sinha Rekha , Li MengChun , Scott Jane , Peeters Monika , Witek James ,   on behalf of the TIGER team
Published: January 2016

Background and Aim

Approximately one‐third of patients with hepatitis C virus (HCV) genotype (GT) 1 infection live in East Asia. This study evaluated the efficacy, pharmacokinetics, safety, and tolerability of simeprevir plus peginterferon alpha‐2a and ribavirin (PR) in HCV GT1‐infected, treatment‐naïve, Asian patients with compensated liver disease.

Methods

This phase III, randomized study (NCT01725529) was conducted in China and South Korea. Patients received simeprevir 150 mg once daily (QD), simeprevir 100 mg QD, or placebo, in combination with PR for 12 weeks. Patients in the simeprevir groups received PR alone for a further 12 or 36 weeks based on response‐guided treatment criteria. Patients in the placebo group received a further 36 weeks of PR alone. The primary efficacy endpoint was sustained virologic response 12 weeks after planned end of treatment (SVR12). Secondary endpoints were safety, pharmacokinetics, tolerability, and patient‐reported outcomes.

Results

Overall, 457 patients were treated; the majority had GT1b infection (452/457 [99%]) and IL28B CC GT (364/457 [80%]). Of the 454 patients who had liver biopsy, 26 had cirrhosis (6%). SVR12 rates were superior for both the simeprevir 100 mg (89%; P = 0.003) and 150 mg (91%; P < 0.001) groups versus placebo (76%). Adverse events were mainly grade 1/2 and occurred at a similar incidence across all treatment groups. Overall, eight patients (2%) discontinued simeprevir or placebo treatment because of adverse events.

Conclusions

Both simeprevir (100 mg and 150 mg QD) plus PR achieved superiority in SVR12 versus placebo plus PR in treatment‐naïve, HCV GT1‐infected, Asian patients and were well tolerated.
Assessment of penile erection methods in rhesus macaques to model pharmacokinetics of antiretroviral drugs and penile infection with simian immunodeficiency virus
Authors: Hayes James , Powell Nathaniel , Lathrop George , Heneine Walid , Dobard Charles W.
Published: January 2016

Background

An established macaque model to assess HIV interventions against penile transmission is currently not available. Physiological changes during penile erections may affect susceptibility to infection and drug pharmacokinetics (PK). Here, we identify methods to establish erections in macaques to evaluate penile transmission, PK, and efficacy under physiologic conditions.

Methods

Penile rigidity and length were evaluated in eight rhesus macaques following rectal electrostimulation (RES), vibratory stimulation (VS), or pharmacological treatment with Sildenafil Citrate (Viagra) or Alprostadil.

Results

Rectal electrostimulation treatment increased penile rigidity (>82%) and length (2.5 ± 0.58 cm), albeit the response was transient. In contrast, VS alone or coupled with Viagra or Alprostadil failed to elicit an erection response.

Conclusion

Rectal electrostimulation treatment elicits transient but consistent penile erections in macaques. High rigidity following RES treatment demonstrates increased blood flow and may provide a functional model for penile PK evaluations and possibly simian immunodeficiency virus (SIV) transmission under erect conditions.
NFκB‐inducing kinase inhibits NFκB activity specifically in neurons of the CNS
Authors: Mao Xianrong , Phanavanh Bounleut , Hamdan Hamdan , Moerman‐Herzog Andréa M. , Barger Steven W.
Published: January 2016

The control ofNFκB inCNSneurons appears to differ from that in other cell types. Studies have reported induction ofNFκB in neuronal cultures and immunostainingin vivo, but others have consistently detected little or no transcriptional activation byNFκB in brain neurons. To test if neurons lack some component of the signal transduction system forNFκB activation, we transfected cortical neurons with several members of this signaling system along with a luciferase‐basedNFκB‐reporter plasmid; RelA was cotransfected in some conditions. No component of theNFκB pathway was permissive for endogenousNFκB activity, and none stimulated the activity of exogenous RelA. Surprisingly, however, the latter was inhibited by cotransfection ofNFκB‐inducing kinase (NIK). Fluorescence imaging of RelA indicated that co‐expression ofNIKsequestered RelA in the cytoplasm, similar to the effect of IκBα.NIK‐knockout mice showed elevated expression of anNFκB‐reporter construct in neuronsin vivo. Cortical neurons cultured fromNIK‐knockout mice showed elevated expression of anNFκB‐reporter transgene. Consistent with data from other cell types, a C‐terminal fragment ofNIKsuppressed RelA activity in astrocytes as well as neurons. Therefore, the inhibitory ability of theNIKC‐terminus was unbiased with regard to cell type. However, inhibition ofNFκB by full‐lengthNIKis a novel outcome that appears to be specific toCNSneurons. This has implications for unique aspects of transcription in theCNS, perhaps relevant to aspects of development, neuroplasticity, and neuroinflammation.

image

Full‐length NIK was found to inhibit (down arrow) transcriptional activation of NFκB in neurons, while it elevated (up arrow) activity in astrocytes. Deletion constructs corresponding to the N‐terminus or C‐terminus also inhibited NFκB in neurons, while only the C‐terminus did so in astrocytes. One possible explanation is that the inhibition in neurons occurs via two different mechanisms, including the potential for a neuron‐specific protein (e.g., one of the 14‐3‐3 class) to create a novel complex in neurons, whereas the C‐terminus may interact directly with NFκB. [Structure of NIK is based on Liu J., Sudom A., Min X., Cao Z., Gao X., Ayres M., Lee F., Cao P., Johnstone S., Plotnikova O., Walker N., Chen G., and Wang Z. (2012) Structure of the nuclear factor κB‐inducing kinase (NIK) kinase domain reveals a constitutively active conformation. J Biol Chem. 287, 27326‐27334); N‐terminal lobe is oriented at top].
Caregiving to persons living with HIV/AIDS: experiences of Vietnamese family members
Authors: Lundberg Pranee C , Doan Thoa Thi Kim , Dinh Thu Thi Xuan , Oach Nhung Kim , Le Phong Hoang
Published: January 2016

Aims and objectives

To examine the experiences of caregiving among Vietnamese family members of persons living with HIV/AIDS.

Background

As the number of persons living with HIV/AIDS increases, the need of family caregivers who can take responsibility for the home care of these persons increases. Vietnam has one of the fastest growing HIV epidemics in Asia.

Design

A descriptive cross‐sectional study with quantitative and qualitative methods was used.

Methods

A purposive sample of 104 family caregivers, both male and female, participated voluntarily by answering a questionnaire of caregiver burden, and 20 of them participated in in‐depth interview.

Results

Female caregivers were mainly mothers and wives while male caregivers were mainly husbands, fathers and siblings. The largest group of family caregivers reported moderate to severe burden. There was no difference between genders in total caregiver burden, but there were several differences between older and younger caregivers in some items of caregiver burden. Five categories of experiences emerged: Different types of caregiving to persons living with HIV/AIDS, cultural and religious issues associated with caregiving, keeping secret to avoid stigma and discrimination, lack of knowledge about disease and provision of care, and fear, anxiety and frustration.

Conclusions

Stigma and discrimination should be decreased by providing knowledge to the general public about HIV/AIDS, in particular about ways of transmission and protection. Special knowledge should be given to family caregivers to enable them to give care to persons living with HIV/AIDS at home. This could be done through culturally appropriate training/intervention programmes in which coping methods should be included. Support group interventions should also be carried through. The results obtained can be used as baseline information.

Relevance to clinical practice

Health care providers should consider gender, age and culture of family members of persons living with HIV/AIDS. Knowledge about HIV/AIDS, provision of care at home and in hospital, and support groups should be developed and implemented.
A Global Value Chain Analysis of the ‘Regional Strategy’ Perspective
Authors: Mudambi Ram , Puck Jonas
Published: January 2016

In this counterpoint paper we argue that the findings presented by the ‘regional strategy’ literature do not capture the full array of global activities of the multinational enterprise (MNE). While this literature makes an important contribution to the field by showing that sales and production activities in the MNE are regionally structured, we argue that this assessment is biased for two reasons. First, this approach overly focuses on geographical location of downstream activities, while disregarding that of knowledge creation and other relevant upstream activities in the MNE. Second, the approach associates the firm's value creation only with its internalized activities and does not capture the value created through any activities that are externalized. Many MNEs rely to a significant extent on value creation outside the firm's legal boundaries. We argue that such omissions are likely to lead to biased interpretations using different theoretical lenses, such as the knowledge‐/resource‐based view, internalization theory and more general transaction cost economics. Based on our reasoning, we provide recommendations for future research both within and beyond the ‘regional strategy’ literature.
Circulating dentinal antigen‐antibody immune complexes during orthodontic tooth movement in rats
Authors: Costa Tânia Maris Pedrini Soares da , Hidalgo Mirian Marubayashi , Consolaro Alberto , Lima Carlos Eduardo de Oliveira , Tanaka Evelise Ono , Trombeta Felipe Braga , Itano Eiko Nakagawa
Published: January 2016

Background

The immunogenic potential of dentin has been reported through dentin‐reactive autoantibodies detection in human and animal model. This study aimed to investigate the formation and diagnostic value of immune complexes formation after autoantibodies production, and soluble dentin antigens levels associated to root resorption, in the course of orthodontic tooth movement, in rat experimental model.

Methods

Forty Wistar rats (n = 8 for each group) were submitted to orthodontic tooth movement, in which the maxillary right first molar was mesially moved by applying of 55 g of force for 3, 7, 14, or 21 days. Untreated group was used as control. Circulating autoantibodies to rat dentinal extract, immune complexes, and soluble dentinal antigen levels were determined by immunoenzyme assays. Additionally, dentinal antigens were analyzed by immunoblot.

Results

Higher serum dentin‐reactive IgG and immune complex levels were detected in the 14‐ and 21‐day groups (p < 0.05 and p < 0.001 respectively) but not in circulating dentinal antigen levels (p > 0.05), as compared to the control group. Reactivity was found to dentinal components with molecular mass (MM) ~120 and ~150 kDa, by immunoblot.

Conclusion

This work represents the first evidence of immune complexes formation and circulating soluble dentin antigens associated to root resorption in orthodontic tooth movement. Immune complexes formation could be used to early diagnosis of external root resorption.
The Akt/mTOR pathway is activated in verrucous carcinoma of the oral cavity
Authors: Chaisuparat Risa , Limpiwatana Seehachart , Kongpanitkul Sanida , Yodsanga Somchai , Jham Bruno C.
Published: January 2016

Background

The Akt/mTOR pathway is activated in many malignancies, including oral squamous cell carcinoma (OSCC). However, the role of the Akt/mTOR pathway in oral verrucous carcinoma (OVC), a low‐grade variant of OSCC, remains unknown. Thus, the objective of this study was to investigate the activation level of important markers of the Akt/mTOR pathway in OVC and to compare the results with OSCC samples.

Methods

The expression of p‐Akt (Thr308), p‐Akt (Ser473), and p‐RPS6 was evaluated by immunohistochemistry in 30 OSCC cases, 18 OVC cases, and 30 control cases (normal epithelium overlying fibromas). Statistical analysis was performed to determine the differences in protein expression between samples.

Results

All OVC cases were positive for p‐Akt (Thr308), p‐Akt (Ser473), and p‐RPS6. There were significant differences in expression level of all studied proteins between OVC and control, as well as between OVC and OSCC. However, OVC showed significant lower staining scores than OSCC.

Conclusions

Our findings demonstrate that the Akt/mTOR pathway is upregulated in OVC, indicating a role for this pathway in the development and progression of this malignancy.
On the Distribution Estimation of Power Threshold Garch Processes
Authors: Gonçalves Esmeralda , Leite Joana , Mendes‐Lopes NazarÉ
Published: January 2016

The aim of this article is to estimate the probability distribution of power threshold generalized autoregressive conditional heteroskedasticity processes by establishing bounds for their finite dimensional laws. These bounds only depend on the parameters of the model and on the distribution function of its independent generating process. The application of this study to some particular models allows us to conjecture that this procedure is an adequate alternative to the corresponding estimation using the empirical distribution functions, particularly useful in the development of control charts for this kind of models.
International Coercion and the Diffusion of Regulatory Data Protection
Authors: Michael Gabriel J.
Published: January 2016

Prior to 1990, regulatory data protection existed only in 14 highly developed countries. Since then, 60 additional countries have adopted regulatory data protection. New adopters include a large number of countries with no domestic pharmaceutical industry. These countries will face higher pharmaceutical prices as a result of offering regulatory data protection. Why would countries that stand to lose from offering regulatory data protection choose to do so? The author argues that the global diffusion of regulatory data protection can be directly traced to international coercion from the United States and the European Union (EU). The US coerces weaker trading partners into adopting regulatory data protection by requiring such protection as a condition of concluding trade agreements or bilateral intellectual property agreements. Meanwhile, the EU coerces applicants by demanding that they adopt such rights during EU accession negotiations, on average four years prior to accession. He tested these claims using a multi‐method research design that combines event history analysis with evidence from leaked US diplomatic cables and public EU accession documents. His findings demonstrate that coercive diffusion can take place by means of threats, and that countries often actively oppose adopting intellectual property rights, but nevertheless adopt them due to international coercion.
Time‐dependent impact of age and comorbidities on long‐term overall survival after liver resection
Authors: Schiergens Tobias S. , Lindenthaler Andrea , Thomas Michael N. , Rentsch Markus , Mittermeier Laura , Brand Katharina , Küchenhoff Helmut , Lee Serene , Guba Markus , Werner Jens , Thasler Wolfgang E.
Published: January 2016

Background & Aims

Advanced age and comorbidities are known to be associated with increased perioperative risks after liver resection. However, the precise impact of these variables on long‐term overall survival (OS) remains unclear. Thus, the aim of this study was to evaluate the confounder‐adjusted, time‐dependent effect of age and comorbidities on OS following hepatectomy for primary and secondary malignancies.

Methods

From a prospective database of 1.143 liver resections, 763 patients treated for primary and secondary malignancies were included. For time‐varying OS calculations, a Cox–Aalen model was fitted. The confounder‐adjusted hazard was compared with mortality tables of the German population.

Results

Overall, age (P = 0.003) and comorbidities (P = 0.001) were associated with shortened OS. However, time‐dependent analysis indicated that age and comorbidities had no impact on OS within 39 and 55 months after resection respectively. From this time on, a significant decline in OS was shown. Subgroup analysis indicated an earlier increase of the effect of age in patients with hepatocellular carcinoma (17 months) than in those with colorectal metastases (70 months). The confounder‐adjusted hazard of 70‐year‐old patients was increased post‐operatively but dropped 66 months after surgery, and the risk of death was comparable to the general population 78 months after resection. At this time, one‐third of patients aged 70 years and older were still alive.

Conclusions

With regard to long‐term outcome, liver resection for both primary and secondary malignancies should not be categorically denied due to age and comorbidities. This information should be considered for the patient selection process and informed consent.
Effect of ready‐to‐use foods for preventing child undernutrition in Niger: analysis of a prospective intervention study over 15 months of follow‐up
Authors: Prudhon Claudine , Langendorf Céline , Roederer Thomas , Doyon Stéphane , Mamaty Abdoul‐Aziz , Woi‐Messe Lynda , Manzo Mahamane L. , de Pee Saskia , Grais Rebecca F.
Published: January 2016

Strategies for preventing undernutrition comprise a range of interventions, including education, provision of complementary food and cash transfer. Here, we compared monthly distributions of two different lipid‐based nutrient supplements (LNS), large‐quantity LNS (LNS‐LQ) and medium‐quantity LNS (LNS‐MQ) for 15 months on prevention of undernutrition among children 6 to 23 months. Both groups also received cash transfer for the first 5 months of the intervention. We conducted a prospective intervention study in Maradi, Niger, between August 2011 and October 2012. Six and 11 villages were randomly allocated to LNS‐LQ/Cash and LNS‐MQ/Cash, respectively. Children measuring 60–80 cm were enrolled in the respective groups and followed up monthly. Poisson regression was used to assess differences between interventions and adjust for baseline characteristics, intervention periods and child‐feeding practices. The analysis included 2586 children (1081 in the LNS‐LQ/Cash group and 1505 in the LNS‐MQ/Cash group). This study suggests that provision of LNS‐LQ (reference) or LNS‐MQ had, overall, similar effect on incidence of severe acute malnutrition (RR = 0.97; 95% CI: 0.67–1.40; P = 0.88), moderate acute malnutrition (RR = 1.20; 95% CI: 0.97–1.48; P = 0.08), severe stunting (RR = 0.94; 95% CI: 0.70–1.26; P = 0.69), moderate stunting (RR = 0.95; 95% CI: 0.76–1.19; P = 0.67) and mortality (RR = 0.83; 95% CI: 0.41–1.65; P = 0.59). Compared with LNS‐LQ, LNS‐MQ showed a greater protective effect on moderate acute malnutrition among children with good dietary adequacy: RR = 0.72; 95% CI: 0.56–0.94; P = 0.01. These results highlight the need to design context‐specific programmes. Provision of LNS‐LQ might be more appropriate when food insecurity is high, while when food security is better, distribution of LNS‐MQ might be more appropriate.
Using implementation research for evidence‐based programme development: a case study from Kenya
Authors: Tumilowicz Alison , McClafferty Bonnie , Neufeld Lynnette M. , Hotz Christine , Pelto Gretel H.
Published: January 2016

The few available studies of programme effectiveness in nutrition find that programmes are less effective than would be predicted from the efficacy trials that are the basis for evidence‐based programming. Some of these are due to gaps in utilisation within households. To a greater extent, these gaps can be attributed to problems in programme design and implementation. ‘Implementation research in nutrition’ is an emerging area of study aimed at addressing this problem, by building an evidence base and a sound theory to design and implement programmes that will effectively deliver nutrition interventions. The purpose of this supplement to Maternal & Child Nutrition is to contribute to this growing area of implementation research. The series of papers presented and the reflections for policymaking and programmes, combined with the reflections on the application of ethnography to this area of inquiry, illustrate the value of systematic research undertaken for the purpose of supporting the design of nutrition interventions that are appropriate for the specific populations in which they are undertaken. © 2015 Blackwell Publishing Ltd
Constraints and opportunities for implementing nutrition‐specific, agricultural and market‐based approaches to improve nutrient intake adequacy among infants and young children in two regions of rural Kenya
Authors: Hotz Christine , Pelto Gretel , Armar‐Klemesu Margaret , Ferguson Elaine F. , Chege Peter , Musinguzi Enock
Published: January 2016

Several types of interventions can be used to improve nutrient intake adequacy in infant and young child (IYC) diets, including fortified foods, home fortification, nutrition education and behaviour change communication (BCC) in addition to agricultural and market‐based strategies. However, the appropriate selection of interventions depends on the social, cultural, physical and economic context of the population. Derived from two rural Kenyan populations, this analysis combined information from: (1) a quantitative analysis to derive a set of food‐based recommendations (FBRs) to fill nutrient intake gaps in IYC diets and identify ‘problem nutrients’ for which intake gaps require solutions beyond currently available foods and dietary patterns, and (2) an ethnographic qualitative analysis to identify contextual factors posing opportunities or constraints to implementing the FBRs, including perceptions of cost, convenience, accessibility and appropriateness of the recommended foods for IYC diets and other social or physical factors that determine accessibility of those foods. Opportunities identified included BCC to increase the acceptability and utilisation of green leafy vegetables (GLV) and small fish and agronomic interventions to increase the productivity of GLV and millet. Value chains for millet, beans, GLV, milk and small fish should be studied for opportunities to increase their accessibility in local markets. Processor‐level interventions, such as partially cooked fortified dry porridge mixes or unfortified cereal mixes incorporating millet and beans, may increase the accessibility of foods that provide increased amounts of the problem nutrients. Multi‐sectoral actors and community stakeholders should be engaged to assess the feasibility of implementing these locally appropriate strategies.
Suitability of hair type for dermatophytes perforation and differential diagnosis of T. mentagrophytes from T. verrucosum
Authors: AL‐Janabi Ali Abdul Hussein S. , AI‐Tememi Nabaa N. , AI‐Shammari Rabab A. , AI‐Assadi Abdul Hadi A.
Published: January 2016

Most of the dermatophyte species have the ability to perforate hair structure and consume its contents of keratin through secretion of keratinase enzyme. Two clinical isolated species of dermatophytes were diagnosed as Trichophyton mentagrophytes var. granulosum and Trichophyton verrucosum. To determine the perforation ability, the isolated fungi were incubated with the hair of four different animals (rabbit, rat, cow and cat) and human hairs with three different colours (black, albino and bleached yellow) for different periods. Variable perforating ability of T. mentagrophytes was shown in rat hair and all types of human hair after 15 days, while other mammalian hairs exhibited resistance to this fungal activity. On the other hand, T. verrucosum was revealed a slow perforating ability, which needed a long time (60 days) for most of tested hairs. Perforation of human black hair could be considered a diagnostic test for differentiation between T. mentagrophytes and T. verrucosum. In conclusion, the treated or untreated human hair was considered more suitable to use as a source of keratin for the growth of dermatophytes than animal hairs. The human black hair was a best type of hair to use in the perforating test for differentiation between T. mentagrophytes and T. verrucosum.
Deconstructing Mediation: A Case Study of theCodWars
Authors: Bakaki Zorzeta
Published: January 2016

In this study,Iexplore the mediation techniques used by an international organization (IO) to settle an international crisis. Specifically,Ihave focused on the use of formal and informal techniques with a case study of theNorthAtlanticTreatyOrganization's (NATO) mediation during theCodWars betweenIceland and theUnitedKingdom. My analysis indicates that a combination of both formal and informal mediation techniques was instrumental in resolving theCodWars conflict. Further research would clarify whether this finding can be generalized to other cases ofNATOmediation and interventions of third parties in addition toNATO.
Reduced kidney function is a risk factor for atrial fibrillation
Authors: Laukkanen Jari A , Zaccardi Francesco , Karppi Jouni , Ronkainen Kimmo , Kurl Sudhir
Published: January 2016

There is limited knowledge on the relationship between kidney function and incidence of atrial fibrillation. Thus, this prospective study was designed to evaluate whether various biomarkers of kidney function are associated to the risk of atrial fibrillation. The study population consisted of 1840 subjects (615 women and 1225 men) aged 61–82 years. Cystatin C‐ and creatinine‐based estimation of glomerular filtration rate (eGFRcys and eGRFcreat, respectively) and urinary albumin/creatinine ratio (ACR) were assessed to investigate their relationship with the risk of atrial fibrillation. During a median follow‐up of 3.7 years, a total of 159 incident atrial fibrillation cases occurred. After adjustment for potential confounders, the risk of atrial fibrillation was increased (hazard ratio 2.74, 95% confidence interval (CI) 1.56–4.81, P < 0.001) in subjects with reduced kidney function (eGFRcys, 15–59 mL/min per 1.73 m2) compared to subjects with normal kidney function (≥90 mL/min per 1.73 m2). Similar results were also found when comparing the respective groups of subjects defined by their eGRFcreat levels (hazard ratio 2.41, CI 1.09–5.30, P = 0.029). Consistently, subjects with ACR ≥300 mg/g had an increased risk of incident atrial fibrillation (hazard ratio 2.16, CI 1.35–2.82, P < 0.001) compared to those with ACR <30 mg/g. Reduced eGFR and albuminuria were associated with an increased risk of atrial fibrillation.
Developing a culturally tailored stroke prevention walking programme for Korean immigrant seniors: a focus group study
Authors: Choi Sarah E. , Kwon Ivy , Chang Emiley , Araiza Daniel , Thorpe Carol Lee , Sarkisian Catherine A.
Published: January 2016

Objectives

To gain better understanding of (i) beliefs and knowledge about stroke; (ii) attitudes about walking for stroke prevention; and (iii) barriers and facilitators to walking among Korean seniors for the cultural tailoring of a stroke prevention walking programme.

Background

Physical inactivity is a major risk factor for stroke. Korean immigrant seniors are one of the most sedentary ethnic groups in the United States.

Design

An explorative study using focus group data. Twenty‐nine Korean immigrant seniors (64–90 years of age) who had been told by a doctor at least once that their blood pressure was elevated participated in 3 focus groups. Each focus group consisted of 8–11 participants.

Methods

Focus group audiotapes were transcribed and analysed using standard content analysis methods.

Results

Participants identified physical and psychological imbalances (e.g. too much work and stress) as the primary causes of stroke. Restoring ‘balance’ was identified as a powerful means of stroke prevention. A subset of participants expressed that prevention may be beyond human control. Overall, participants acknowledged the importance of walking for stroke prevention, but described barriers such as lack of personal motivation and unsafe environment. Many participants believed that providing opportunities for socialisation while walking and combining walking with health information sessions would facilitate participation in and maintenance of a walking programme.

Conclusions

Korean immigrant seniors believe strongly that imbalance is a primary cause of stroke. Restoring balance as a way to prevent stroke is culturally special among Koreans and provides a conceptual base in culturally tailoring our stroke prevention walking intervention for Korean immigrant seniors.

Implications for practice

A stroke prevention walking programme for Korean immigrant seniors may have greater impact by addressing beliefs about stroke causes and prevention such as physical and psychological imbalances and the importance of maintaining emotional well‐being.
Airway remodelling in asthma: It's not going away
Authors: King Gregory G. , Noble Peter B.
Published: January 2016

See article, page 297
Perils and Potentials of Self-Selected Entry to Epidemiological Studies and Surveys
Authors: Keiding Niels , Louis Thomas A.
Published: January 2016

Low front-end cost and rapid accrual make Web-based surveys and enrolment in studies attractive, but participants are often self-selected with little reference to a well-defined study base. Of course, high quality studies must be internally valid (validity of inferences for the sample at hand), but Web-based enrolment reactivates discussion of external validity (generalization of within-study inferences to a target population or context) in epidemiology and clinical trials. Survey research relies on a representative sample produced by a sampling frame, prespecified sampling process and weighting that maps results to an intended population. In contrast, recent analytical epidemiology has shifted the focus away from survey-type representativity to internal validity in the sample. Against this background, it is a good time for statisticians to take stock of our role and position regarding surveys, observational research in epidemiology and clinical studies. The central issue is whether conditional effects in the sample (the study population) may be transported to desired target populations. Success depends on compatibility of causal structures in study and target populations, and will require subject matter considerations in each concrete case. Statisticians, epidemiologists and survey researchers should work together to increase understanding of these challenges and to develop improved tools to handle them.
Protothecal bursitis after simultaneous kidney/liver transplantation: a case report and review
Authors: Ramírez I. , Nieto‐Ríos J.F. , Ocampo‐Kohn C. , Aristizábal‐Alzate A. , Zuluaga‐Valencia G. , Muñoz Maya O. , Pérez J.C.
Published: January 2016

Solid organ transplantation is an accepted therapy for end‐stage diseases of the kidneys, liver, heart, and lungs. Unfortunately, transplantation is associated with infectious complications. Here, we present a case report of Prototheca wickerhamii olecranon bursitis and review all of the cases in solid organ transplant (SOT) recipients published in the literature to date. In our patient, the infection resolved with surgical therapy and limited antifungal therapy, and no symptoms have recurred over 24 months of follow‐up. A review of the literature suggests that 50% of SOT recipients with Prototheca infection present with disseminated infection, and the overall mortality is 75%. More studies are required to determine the optimal management of protothecosis in this population.
Nucleocytoplasmic trafficking is essential for BAK1‐ and BKK1‐mediated cell‐death control
Authors: Du Junbo , Gao Yang , Zhan Yanyan , Zhang Shasha , Wu Yujun , Xiao Yao , Zou Bo , He Kai , Gou Xiaoping , Li Guojing , Lin Honghui , Li Jia
Published: January 2016

BRI1‐ASSOCIATED KINASE 1 (BAK1) was initially identified as a co‐receptor of the brassinosteroid (BR) receptor BRI1. Genetic analyses also revealed that BAK1 and its closest homolog BAK1‐LIKE 1 (BKK1) regulate a BR‐independent cell‐death control pathway. The double null mutant bak1 bkk1 displays a salicylic acid‐ and light‐dependent cell‐death phenotype even without pathogen invasion. Molecular mechanisms of the spontaneous cell death mediated by BAK1 and BKK1 remain unknown. Here we report our identification of a suppressor of bak1 bkk1 (sbb1–1). Genetic analyses indicated that cell‐death symptoms in a weak double mutant, bak1–3 bkk1–1, were completely suppressed by the loss‐of‐function mutation in SBB1, which encodes a nucleoporin (NUP) 85‐like protein. Genetic analyses also demonstrated that individually knocking out three other nucleoporin genes from the SBB1‐located sub‐complex was also able to rescue the cell‐death phenotype of bak1–3 bkk1–1. In addition, a DEAD‐box RNA helicase, DRH1, was identified in the same protein complex as SBB1 via a proteomic approach. The drh1 mutation also rescues the cell‐death symptoms of bak1–3 bkk1–1. Further analyses indicated that export of poly(A)+ RNA was greatly blocked in the nup and drh1 mutants, resulting in accumulation of significant levels of mRNAs in the nuclei. Over‐expression of a bacterial NahG gene to inactivate salicylic acid also rescues the cell‐death phenotype of bak1–3 bkk1–1. Mutants suppressing cell‐death symptoms always showed greatly reduced salicylic acid contents. These results suggest that nucleocytoplasmic trafficking, especially of molecules directly or indirectly involved in endogenous salicylic acid accumulation, is critical in BAK1‐ and BKK1‐mediated cell‐death control.
Assembly of Peroxisomal Membrane Proteins via the Direct Pex19p‐Pex3p Pathway
Authors: Liu Yuqiong , Yagita Yuichi , Fujiki Yukio
Published: January 2016

Correct targeting of peroxisomal membrane proteins (PMPs) is essential for the formation and maintenance of functional peroxisomes. Activities of Pex19p to interact with PMPs on one hand and Pex3p on the other, including formation of ternary complexes between Pex19p, PMP and Pex3p, strongly support posttranslational translocation of PMPs via the Pex19p‐ and Pex3p‐dependent direct pathway, termed the class I pathway. However, it remains elusive whether Pex19p‐PMP complexes are indeed capable of being imported into peroxisomal membranes through the interaction between Pex19p and Pex3p. We resolve this issue by investigating the targeting process of several topologically distinct PMPs, including multimembrane spanning PMPs. We show here that Pex19p forms cytosolic complexes with PMPs and directly translocates them to peroxisomes. Using a semi‐intact mammalian cell‐based import assay system, we prove that PMPs in the cytosolic complexes are imported into peroxisomes via the interaction between cargo‐loaded Pex19p and Pex3p. Furthermore, we demonstrate for the first time that peroxisomal targeting of ATAD1, an N‐terminally signal‐anchored protein that resides on both mitochondria and peroxisomes, is also achieved through the Pex19p‐ and Pex3p‐dependent class I pathway. Together, our results suggest that translocation of PMPs via the class I pathway is a common event in mammalian cells.
INVITED REVIEW—IMAGE REGISTRATION IN VETERINARY RADIATION ONCOLOGY: INDICATIONS, IMPLICATIONS, AND FUTURE ADVANCES
Authors: Feng Yang , Lawrence Jessica , Cheng Kun , Montgomery Dean , Forrest Lisa , Mclaren Duncan B. , McLaughlin Stephen , Argyle David J. , Nailon William H.
Published: January 2016

The field of veterinary radiation therapy (RT) has gained substantial momentum in recent decades with significant advances in conformal treatment planning, image‐guided radiation therapy (IGRT), and intensity‐modulated (IMRT) techniques. At the root of these advancements lie improvements in tumor imaging, image alignment (registration), target volume delineation, and identification of critical structures. Image registration has been widely used to combine information from multimodality images such as computerized tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) to improve the accuracy of radiation delivery and reliably identify tumor‐bearing areas. Many different techniques have been applied in image registration. This review provides an overview of medical image registration in RT and its applications in veterinary oncology. A summary of the most commonly used approaches in human and veterinary medicine is presented along with their current use in IGRT and adaptive radiation therapy (ART). It is important to realize that registration does not guarantee that target volumes, such as the gross tumor volume (GTV), are correctly identified on the image being registered, as limitations unique to registration algorithms exist. Research involving novel registration frameworks for automatic segmentation of tumor volumes is ongoing and comparative oncology programs offer a unique opportunity to test the efficacy of proposed algorithms.