bluuebunny/crossref_metadata_2025 huggingface dataset:
Ecology has contrasting effects on genetic variation within species versus rates of molecular evolution across species in water beetles
Authors: Fujisawa Tomochika , Vogler Alfried P. , Barraclough Timothy G.
Published: December 2014

Comparative analysis is a potentially powerful approach to study the effects of ecological traits on genetic variation and rate of evolution across species. However, the lack of suitable datasets means that comparative studies of correlates of genetic traits across an entire clade have been rare. Here, we use a large DNA-barcode dataset (5062 sequences) of water beetles to test the effects of species ecology and geographical distribution on genetic variation within species and rates of molecular evolution across species. We investigated species traits predicted to influence their genetic characteristics, such as surrogate measures of species population size, latitudinal distribution and habitat types, taking phylogeny into account. Genetic variation of cytochrome oxidase I in water beetles was positively correlated with occupancy (numbers of sites of species presence) and negatively with latitude, whereas substitution rates across species depended mainly on habitat types, and running water specialists had the highest rate. These results are consistent with theoretical predictions from nearly-neutral theories of evolution, and suggest that the comparative analysis using large databases can give insights into correlates of genetic variation and molecular evolution.
The progenitor state is maintained by lysine-specific demethylase 1-mediated epigenetic plasticity during Drosophila follicle cell development
Authors: Lee Ming-Chia , Spradling Allan C.
Published: December 2014

Progenitors are early lineage cells that proliferate before the onset of terminal differentiation. Although widespread, the epigenetic mechanisms that control the progenitor state and the onset of differentiation remain elusive. By studying Drosophila ovarian follicle cell progenitors, we identified lysine-specific demethylase 1 (lsd1) and CoRest as differentiation regulators using a GAL4∷GFP variegation assay. The follicle cell progenitors in lsd1 or CoRest heterozygotes prematurely lose epigenetic plasticity, undergo the Notch-dependent mitotic-endocycle transition, and stop dividing before a normal number of follicle cells can be produced. Simultaneously reducing the dosage of the histone H3K4 methyltransferase Trithorax reverses these effects, suggesting that an Lsd1/CoRest complex times progenitor differentiation by controlling the stability of H3K4 methylation levels. Individual cells or small clones initially respond to Notch; hence, a critical level of epigenetic stabilization is acquired cell-autonomously and initiates differentiation by making progenitors responsive to pre-existing external signals.
Pioneer transcription factors in cell reprogramming
Authors: Iwafuchi-Doi Makiko , Zaret Kenneth S.
Published: December 2014

A subset of eukaryotic transcription factors possesses the remarkable ability to reprogram one type of cell into another. The transcription factors that reprogram cell fate are invariably those that are crucial for the initial cell programming in embryonic development. To elicit cell programming or reprogramming, transcription factors must be able to engage genes that are developmentally silenced and inappropriate for expression in the original cell. Developmentally silenced genes are typically embedded in “closed” chromatin that is covered by nucleosomes and not hypersensitive to nuclease probes such as DNase I. Biochemical and genomic studies have shown that transcription factors with the highest reprogramming activity often have the special ability to engage their target sites on nucleosomal DNA, thus behaving as “pioneer factors” to initiate events in closed chromatin. Other reprogramming factors appear dependent on pioneer factors for engaging nucleosomes and closed chromatin. However, certain genomic domains in which nucleosomes are occluded by higher-order chromatin structures, such as in heterochromatin, are resistant to pioneer factor binding. Understanding the means by which pioneer factors can engage closed chromatin and how heterochromatin can prevent such binding promises to advance our ability to reprogram cell fates at will and is the topic of this review.
Tuning the phase transition of ZnO thin films through lithography: an integrated bottom-up and top-down processing
Authors: Malfatti Luca , Pinna Alessandra , Enzo Stefano , Falcaro Paolo , Marmiroli Benedetta , Innocenzi Plinio
Published: December 2014

An innovative approach towards the physico-chemical tailoring of zinc oxide thin films is reported. The films have been deposited by liquid phase using the sol–gel method and then exposed to hard X-rays, provided by a synchrotron storage ring, for lithography. The use of surfactant and chelating agents in the sol allows easy-to-pattern films made by an organic–inorganic matrix to be deposited. The exposure to hard X-rays strongly affects the nucleation and growth of crystalline ZnO, triggering the formation of two intermediate phases before obtaining a wurtzite-like structure. At the same time, X-ray lithography allows for a fast patterning of the coatings enabling microfabrication for sensing and arrays technology.
Application of a single‐colony coculture technique to the isolation of hitherto unculturable gut bacteria
Authors: Tanaka Yoshiki , Benno Yoshimi
Published: December 2014

Molecular studies have led to postulation of a relationship between gut microbiota and certain diseases. However, because studies of hitherto uncultured species in vivo are essential for characterizing the biology and pathogenic properties of gut bacteria, techniques for culturing and isolating such bacteria must be developed. Here, a technique is described that partially overcomes the obstacles that prevent detection of interbacterial communication in vitro and are thus responsible for the failure to culture certain bacterial species. For this purpose, a ring with a membrane filter at the bottom was designed and a relatively simple nutrient medium was used instead of conventional media. Gut bacteria were cocultivated in soft agar separated by the membrane filter to simulate interbacterial communication in vitro. Use of this soft agar coculture technique led to the successful isolation of hitherto uncultured bacteria and the demonstration of multistage interbacterial communication among gut bacteria in vitro. Cultivation and isolation of single colonies of bacteria that require other bacteria for growth will enhance efforts to better understand the physiological and pathogenic roles of gut microbiota.
Research gaps in the care of women with female genital mutilation: an analysis
Authors: Abdulcadir J , Rodriguez MI , Say L
Published: December 2014

Female genital mutilation (FGM) includes procedures involving the partial or total removal of the external female genitals for non‐therapeutic reasons. They can have negative psychosexual and health consequences that need specific care. In this paper, we review some key knowledge gaps in the clinical care of women with FGM, focusing on obstetric outcomes, surgical interventions (defibulation and clitoral reconstruction), and the skills and training of healthcare professionals involved in the prevention and management of FGM. We identify research priorities to improve the evidence necessary to establish guidelines for the best multidisciplinary care, communication, and prevention, and to improve health‐promotion measures for women with FGM.
Acceleration of small bowel transit in a canine hypermotility model with intestinal electrical stimulation
Authors: Wang Wei Feng , Yin Jie Yun , Chen Jian De DZ
Published: December 2014

Objective

Few studies have been performed on the effect of intestinal electrical stimulation (IES) on intestinal dysmotility. This study aimed to investigate the small intestine transit (SIT) in a canine model of intestinal hypermotility when applying IES.

Method

Six hound bitches were surgically prepared with two chronic intestinal fistulas, intestinal serosal electrodes of which the proximal pair was used for serosal IES. Pacing wires were attached to a manometric catheter for mucosal IES. A nitrogen oxide synthase inhibitor, Nω‐nitro‐L‐arginine (LNNA) was used to induce intestinal motility. SIT was measured during IES. The study consisted of four randomized sessions: session 1 (LNNA), session 2 (LNNA plus serosal IES), session 3 (LNNA plus mucosal IES) and session 4 (control).

Results

The intestine transit was slowed down from 31.7 ± 6.1 min in the control session to 49.0 ± 6.2 min after using LNNA (P = 0.003). Both mucosal and serosal IES accelerated SIT compared with the LNNA session. The SIT time was reduced to 17.7 ± 3.4 min in the mucosal IES session (P = 0.006 vs LNNA) and 27.5 ± 6.3 min in the serosal IES session (P = 0.020 vs LNNA). No difference was noted in the SIT time between mucosal and serosal IES (P = 0.128).

Conclusion

IES significantly accelerates delayed SIT in a hypermotility model and intraluminal stimulation is as effective as a serosal one for IES, suggesting that IES may have a therapeutic potential for improving intestinal motility.
Long‐term outcome in patients with obscure gastrointestinal bleeding after capsule endoscopy
Authors: Tan Wei , Ge Zhi Zheng , Gao Yun Jie , Li Xiao Bo , Dai Jun , Fu Seng Wang , Zhang Yao , Xue Han Bing , Zhao Yun Jia
Published: December 2014

Objective

This study aimed to identify the risk factors associated with rebleeding and long‐term outcomes after capsule endoscopy (CE) for obscure gastrointestinal bleeding (OGIB) in a follow‐up study.

Methods

Data of consecutive patients who underwent CE due to OGIB from June 2002 to January 2012 were retrospectively reviewed. The Cox proportional hazard model was used to evaluate the risk factors associated with rebleeding, while Kaplan–Meier survival curves and the log–rank test were used to analyze cumulative rebleeding rates.

Results

The overall rebleeding rate after CE in patients with OGIB was 28.6% (97/339) during a median follow‐up of 48 months (range 12–112 months). Multivariate analysis showed that age ≥60 years (hazard ratio [HR] 2.473, 95% confidence interval [CI] 1.576–3.881, P = 0.000), positive CE findings (HR 3.393, 95% CI 1.931–5.963, P = 0.000), hemoglobin ≤70 g/L before CE (HR 2.010, 95% CI 1.261–3.206, P = 0.003), nonspecific treatments (HR 2.500, 95% CI 1.625–3.848, P = 0.000) and the use of anticoagulants, antiplatelet or non‐steroidal anti‐inflammatory drugs after CE (HR 2.851, 95% CI 1.433–5.674, P = 0.003) were independent risk factors associated with rebleeding. Univariate analysis showed that chronic hepatitis was independently associated with rebleeding in CE‐negative patients (P = 0.021).

Conclusions

CE has a significant impact on the long‐term outcome of patients with OGIB. Further investigation and close follow‐up in patients with OGIB and those with negative CE findings are necessary.
Intrinsic foot muscle and plantar tissue changes in type 2 diabetes mellitus
Authors: Kumar C.G. Shashi , Rajagopal K.V. , Hande H. Manjunath , Maiya Arun G. , Mayya Shreemathi S.
Published: December 2014

Background

Diabetes mellitus is a metabolic disorder with involvement of the neurovascular and muscular system. Peripheral neuropathy (PN) is thought to be the principal cause of foot complications in type 2 diabetes mellitus (T2DM). However, foot evaluation using ultrasonography early in the course of diabetes has not gained due importance. The aim of the present study was to evaluate the thickness of intrinsic foot muscles, plantar skin, plantar fascia, and plantar fat pad in T2DM subjects with and without PN using musculoskeletal ultrasonography.

Methods

This study was conducted in 30 T2DM subjects with and without PN and 30 age‐matched non‐diabetes mellitus (NDM) subjects. After detailed clinical evaluation, high‐frequency musculoskeletal ultrasonography was used to measure the thickness of the intrinsic foot muscles and plantar tissue thickness under the metatarsals. Data were analyzed using independent t‐tests to compare T2DM groups with NDM subjects, and one‐way ANOVA followed by Tukey's honestly significant difference test for between‐ and within‐group analyses.

Results

There was a significant reduction in the thickness of the intrinsic foot muscles and plantar tissue in T2DM compared with NDM subjects (P < 0.05). However, there were differences in intrinsic foot muscle and plantar tissue thickness between T2DM subjects with and without PN.

Conclusion

There was a substantial decrease in intrinsic foot muscle and plantar tissue thickness in T2DM compared with NDM subjects, indicating that structural changes appear in the foot before PN develops. The techniques used in this study cannot exclude the possibility that neuropathic changes that are clinically undetectable may develop in parallel with changes in plantar tissues.
Outcomes of singleton and twin pregnancies complicated by pre‐existing diabetes and gestational diabetes: A population‐based study in Alberta, Canada, 2005–11
Authors: Lai Florence Y. , Johnson Jeffrey A. , Dover Doug , Kaul Padma
Published: December 2014

Background

We assessed the prevalence and pregnancy outcomes of pre‐existing diabetes mellitus (pre‐DM) and gestational diabetes mellitus (GDM) in Alberta, Canada, 2005–11.

Methods

327 198 singleton and 5552 twin pregnancies resulting in live births or stillbirths were included. The odds ratios of adverse outcomes were evaluated comparing pre‐DM with no diabetes and GDM with no diabetes, controlling for maternal characteristics.

Results

Diabetes complicated 6.3% of pregnancies, with 88% being GDM. In singleton pregnancies, pre‐DM and GDM were associated with increased risks of pre‐eclampsia (adjusted odds ratio [aOR] = 3.38 and 1.83, respectively), cesarean delivery (aOR 2.53, 1.55), spontaneous preterm (aOR 4.20, 1.71), and labor‐induced preterm (aOR 3.82, 2.00) in the mother, and macrosomia (aOR 2.11, 1.30), shoulder dystocia (aOR 1.54, 1.32), congenital anomalies (aOR 1.61, 1.20), and neonatal intensive care unit (NICU) admissions (aOR 3.81, 1.60) in the infants. In addition, pre‐DM was associated with an increased likelihood of stillbirth (aOR 3.73) and neonatal death (aOR 2.00) compared with non‐diabetic pregnancies. In twin pregnancies, pre‐DM was associated with increased risks of spontaneous (aOR 3.54) and labor‐induced (aOR 3.57) preterm births, large for gestational age (LGA) infants (aOR 3.73), congenital anomalies (aOR 3.05) and NICU admissions (aOR 2.91); GDM was associated with an increased risk of pre‐eclampsia (aOR 1.54), cesarean delivery (aOR 1.57), and LGA infants (aOR 1.63).

Conclusions

Pre‐existing diabetes confers higher risks than GDM. Diabetes is associated with adverse outcomes in singleton and twin pregnancies, and the increased risks are generally similar or less in twins, probably due to their higher “baseline” risks and closer clinical monitoring.
Lower irisin level in patients with type 2 diabetes mellitus: A case‐control study and meta‐analysis
Authors: Zhang Chun , Ding Zhi , Lv Guoqiang , Li Jianping , Zhou Ping , Zhang Junfeng
Published: December 2014

Background

Irisin is a newly identified myokine in mice and humans. Many studies have reported irisin concentrations in patients with type 2 diabetes mellitus (T2DM). The large variations in irisin concentrations in different studies may be attributable to differences in sample size or populations. The aim of the present study was to establish an accurate confidence interval of irisin levels in T2DM patients using a case‐control study and large‐scale meta‐analysis.

Methods

Serum irisin concentrations were determined in newly diagnosed T2DM patients (n = 50) and age‐ and body mass index‐matched controls (n = 50) in a case‐control study. Further, a meta‐analysis was conducted to verify whether circulating irisin concentrations are lower in patients with T2DM. All publications regarding the association between irisin and T2DM in Medline, PubMed and EMBase were retrieved using the keywords “irisin” and “myokine”. Review Manager 5.0 (Cochrane Collaboration, Oxford, UK) was used to pool the data.

Results

In the case‐control study, irisin concentrations were lower in newly diagnosed T2DM patients compared with healthy controls. In the meta‐analysis, the pooled data indicated that irisin concentrations were 24.46 ng/mL (95% confidence interval [CI] 9.31, 39.60; P = 0.002) lower in T2DM patients than healthy controls.

Conclusions

This study confirmed that circulating irisin concentrations were significantly lower in patients with T2DM.
The influence of industry actions on the availability of alcoholic beverages in the African region
Authors: Babor Thomas F. , Robaina Katherine , Jernigan David
Published: December 2014

Aims

The alcohol beverage industry has been expanding its corporate social responsibility and other business activities in sub‐Saharan Africa. The aim of this paper is to evaluate the effects of these activities on the physical, economic, psychological and social availability of alcohol in the region.

Methods

Narrative review. Source materials came from the business press, industry sources (websites, annual reports, press releases, conference proceedings) and the scientific literature published since 2000.

Results

The alcohol industry has intensified its activities in the African region, through their funding of social aspect organizations, technical publications, policy workshops and other corporate social responsibility activities. Marketing campaigns, new product designs and the development of industry‐civil society partnerships have increased. There is evidence that the alcohol industry also engages in lobbying, information dissemination and legal action to thwart effective public health measures.

Conclusions

The corporate social responsibility activities of the global alcohol industry have provided a vehicle to promote industry‐favorable policies and increase the physical, economic, social and psychological availability of alcohol.
Safety of sublingual immunotherapy Timothy grass tablet in subjects with allergic rhinitis with or without conjunctivitis and history of asthma
Authors: Maloney J. , Durham S. , Skoner D. , Dahl R. , Bufe A. , Bernstein D. , Murphy K. , Waserman S. , Berman G. , White M. , Kaur A. , Nolte H.
Published: December 2014

Background

Patients with asthma may be more susceptible to adverse events (AEs) with sublingual immunotherapy tablet (SLIT‐tablet) treatment, such as severe systemic reactions and asthma‐related events. Using data from eight trials of grass SLIT‐tablet in subjects with allergic rhinitis with/without conjunctivitis (AR/C), AE frequencies were determined in adults and children with and without reported asthma.

Methods

Data from randomized, double‐blind, placebo‐controlled trials of Timothy grass SLIT‐tablet MK‐7243 (2800 BAU/75 000 SQ‐T, Merck/ALK‐Abelló) were pooled for post hoc analyses. Subjects with uncontrolled and severe asthma were excluded from the trials. Frequencies for treatment‐emergent AEs (TEAEs), local allergic swelling (mouth or throat), systemic allergic reactions, and asthma‐related treatment‐related AEs (TRAEs) were calculated.

Results

Among adults (n = 3314) and children (n = 881), 24% and 31%, respectively, had reported asthma. No serious local allergic swellings or serious systemic allergic reactions occurred in subjects with asthma treated with SLIT‐tablet. There was no evidence of increased TEAEs, systemic allergic reactions, or severe local allergic swellings in adults or children with asthma treated with grass SLIT‐tablet versus subjects without asthma in or outside of pollen season. There were 6/120 asthma‐related TRAEs assessed as severe with grass SLIT‐tablet and 2/60 with placebo, without a consistent trend among subjects with and without asthma (5 and 3 events, respectively).

Conclusions

In the AR/C subjects with reported well‐controlled mild asthma included in these studies, grass SLIT‐tablet did not increase TEAE frequency, severe local allergic swelling, or systemic allergic reactions versus subjects without asthma. There was no indication that treatment led to acute asthma worsening.
Decreased umbilical orexin‐A level is associated with idiopathic polyhydramnios
Authors: Cho Geum Joon , Hong Hye‐Ri , Kim Suhng Wook , Hong Soon Cheol , Oh Min‐Jeong , Kim Hai Joon
Published: December 2014

Objective

To evaluate the association between orexin‐A level and idiopathic polyhydramnios.

Design

Case‐control study.

Setting

Tertiary‐level university hospital.

Population

Ten term pregnant women with idiopathic polyhydramnios and, as the control group, 20 pregnant women with normal amniotic fluid levels.

Methods

Amniotic fluid level was measured at admission for delivery using enzyme‐linked immunosorbent assay. Maternal blood was obtained from a cannulated vein immediately before delivery, and umbilical blood was collected at the time of delivery, before the separation of the placenta.

Main outcome measures

Maternal and umbilical levels of orexin‐A.

Results

Mean umbilical serum orexin‐A level was significantly lower than maternal serum orexin‐A level. Umbilical serum orexin‐A level was positively correlated with maternal serum orexin‐A level, but negatively correlated with amniotic fluid index and birthweight. Umbilical serum orexin‐A level was lower in the idiopathic polyhydramnios group than in the control group. However, no difference in maternal serum orexin‐A level was observed between the two groups.

Conclusions

Idiopathic polyhydramnios was associated with decreased umbilical serum orexin‐A levels. Our results provide evidence that orexin‐A expression may be involved in amniotic fluid regulation, causing polyhydramnios by downregulation.
Information and knowledge about Down syndrome among women and partners after first trimester combined testing
Authors: Ternby Ellen , Ingvoldstad Charlotta , Annerén Göran , Lindgren Peter , Axelsson Ove
Published: December 2014

We assessed reasons among women and partners for choosing combined ultrasound‐biochemistry testing, information and knowledge about Down syndrome and decisions concerning invasive procedures and termination of pregnancy in a prospective cohort study in Uppsala County. In all 105 pregnant women and 104 partners coming for a combined ultrasound‐biochemistry test answered a questionnaire. The most common reason for a combined ultrasound‐biochemistry test was “to perform all tests possible to make sure the baby is healthy”. Internet and midwives were the most common sources of information. Seventy‐two percent had not received information on what it means to live with a child with Down syndrome. Many expectant parents perceived information as insufficient. Both women and partners had varying or low levels of knowledge about medical, cognitive and social consequences of Down syndrome. Twenty‐five percent had not decided on an invasive test if indicated and only 42% would consider termination of pregnancy with a Down syndrome diagnosis.
Robot‐assisted surgery in cervical cancer patients reduces the time to normal activities of daily living
Authors: Asciutto Katrin C. , Kalapotharakos Grigorios , Löfgren Mats , Högberg Thomas , Borgfeldt Christer
Published: December 2014

Objective

To evaluate current surgical cervical cancer treatment in Sweden 2008–12.

Design and setting

Analysis of data in the Swedish National Quality Register for Gynecological Surgery (GynOP).

Sample

A total of 249 cervical cancer patients undergoing surgery.

Methods

Analysis of prospectively gathered preoperative and postoperative data including patient‐reported information.

Main outcome measures

Mean operating time, blood loss/transfusion, length of hospital stay, return to activities of daily living.

Results

The patients undergoing laparoscopic robot‐assisted surgery (n = 64) or laparotomy (n = 185) did not differ in age, body mass index, American Society of Anesthesiologists score, International Federation of Gynecology and Obstetrics (FIGO) stage or mean operating time. Blood loss was higher in the laparotomy group (p < 0.001). Thirteen patients in the laparotomy group (7%) received a blood transfusion, but none in the robot group. Intraoperative complications were more common in the laparotomy group (p = 0.03). Re‐admission or operations did not differ between the groups. The number of pelvic lymph nodes removed was significantly higher in the laparotomy group (median 31 vs. 24, p < 0.001). There was no difference regarding the number of patients with lymph node metastases in the two groups. The postoperative length of hospital stay was longer in the laparotomy group compared with the robot group (6.1 days vs. 2.1 days, p = 0.01). The patient‐reported time to resume normal activities of daily living was longer in the laparotomy than the robot group (13.4 days vs. 9.7 days, p = 0.04).

Conclusions

Laparoscopic robotic‐assisted surgery is preferable to laparotomy for cervical cancer patients because it entails a significantly shorter hospital stay, less blood loss, fewer intraoperative complications and shorter time to normal daily activities.
Comparative efficacy of up to 50% partial fish meal replacement with fermented soybean meal or enzymatically prepared soybean meal on growth performance, nutrient digestibility and fecal microflora in weaned pigs
Authors: Jeong Jin Suk , Kim In Ho
Published: December 2014

This study was conducted to determine the comparative efficacy of partial fish meal (FM) replacement (up to 50%) with fermented soybean meal (FSBM; SoELAB, PepSoyGen and Soytide) or enzymatically prepared SBM (HP 300) on growth performance, nutrient digestibility and fecal microflora in weaned pigs. A total of 100 weaned pigs (body weight 6.59 ± 0.29 kg) were used in experimental feeding trials, lasting for up to 6 weeks, and were randomly allotted to five groups with four block replicates of five pigs per pen serving as one block. Dietary treatments were as follows: (i) 100% FM, (ii) 50% FM + 50% SoELAB‐54, (iii) 50% FM + 50% PepSoyGen, (iv) 50% FM + 50% Soytide and (v) 50% FM + 50% HP 300. Concerning growth performance, none of the treated SBM preparations demonstrated any significantly different effect compared with FM treatment. With respect to nutrient digestibility, SoELAB and HP 300 treatments demonstrated no significant difference compared with FM treatment. Lastly, none of the SBM preparations demonstrated any significant differences in animal fecal score and all of the differentially treated SBM increased fecal Lactobacillus counts, while maintaining similar Escherichia coli counts compared with FM treatment.
Amphibian Hotspots and Conservation Priorities in Eastern Cuba Identified by Species Distribution Modeling
Authors: Fong G. Ansel , Viña Dávila Nicasio , López‐Iborra Germán M.
Published: December 2014

The high rate of amphibian endemism and the severe habitat modification in the Caribbean islands make them an ideal place to test if the current protected areas network might protect this group. In this study, we model distribution and map species richness of the 40 amphibian species from eastern Cuba with the objectives of identify hotspots, detect gaps in species representation in protected areas, and select additional areas to fill these gaps. We used two modeling methods, Maxent and Habitat Suitability Models, to reach a consensus distribution map for each species, then calculate species richness by combining specific models and finally performed gap analyses for species and hotspots. Our results showed that the models were robust enough to predict species distributions and that most of the amphibian hotspots were represented in reserves, but 50 percent of the species were incompletely covered and Eleutherodactylus rivularis was totally uncovered by the protected areas. We identified 1441 additional km2 (9.9% of the study area) that could be added to the current protected areas, allowing the representation of every species and all hotspots. Our results are relevant for the conservation planning in other Caribbean islands, since studies like this could contribute to fill the gaps in the existing protected areas and to design a future network. Both cases would benefit from modeling amphibian species distribution using available data, even if they are incomplete, rather than relying only in the protection of known or suspected hotspots.
Design, Synthesis, and Biological Evaluation of Novel Benzoyl Diarylamine/ether Derivatives as Potential Anti‐HIV‐1 Agents
Authors: Zhang Lingzi , Guo Jian , Liu Xin , Liu Huiqing , De Clercq Erik , Pannecouque Christophe , Liu Xinyong
Published: December 2014

A series of benzoyl diarylamine/ether derivatives were designed, synthesized, and evaluated for their activity against human immunodeficiency virus (HIV) in MT‐4 cells. Three compounds (3b, 5a, and 6a1) exhibited moderate activities against wild‐type (wt) HIV‐1 with EC50 values ranging from 11 to 56 μm. Among them, compound 5a was the most potent inhibitor with a novel chemical skeleton, affording a new lead compound for further molecular optimization. An enzyme assay was also implemented to confirm the binding target of the active compounds represented by 6a1. Molecular simulation studies on compound 5a, 6a1, and 7a4 were carried out to understand their binding mode with wt HIV‐1 reverse transcriptase (RT) and provided useful information for further rational design of NNRTIs.
Epidemiology of anaphylaxis
Authors: Tejedor Alonso M. A. , Moro Moro M. , Múgica García M. V.
Published: December 2014

Knowledge about the epidemiology of anaphylaxis is based on data from various sources: clinical practice, large secondary clinical and administrative databases of primary care or hospitalized patients, and recent surveys with representative samples of the general population. As several similar results are often reported in several publications and populations, such findings are highly like to be robust. One such finding is that the incidence and prevalence of anaphylaxis are higher than previously thought. Publications from the last 5 years reveal an incidence of between 50 and 112 episodes per 100 000 person‐years; estimated prevalence is 0.3–5.1% depending on the rigour of the definitions used. Figures are higher in children, especially those aged 0–4 years. Publications from various geographical areas based on clinical and administrative data on hospitalized patients suggest that the frequency of admissions due to anaphylaxis has increased (5–7‐fold in the last 10–15 years). Other publications point to a geographic gradient in the incidence of anaphylaxis, with higher frequencies recorded in areas with few hours of sunlight. However, these trends could be the result of factors other than a real change in the incidence of anaphylaxis, such as changes in disease coding and in the care provided. Based on data from the records of voluntary declarations of death by physicians and from large national databases, death from anaphylaxis remains very infrequent and stands at 0.35–1.06 deaths per million people per year, with no increases observed in the last 10–15 years. Although anaphylaxis can be fatal, recurrence of anaphylaxis – especially that associated with atopic diseases and hymenoptera stings – affects 26.5–54% of patients.
T cell receptor binding affinity governs the functional profile of cancer-specific CD8+ T cells
Authors: Tan M P , Gerry A B , Brewer J E , Melchiori L , Bridgeman J S , Bennett A D , Pumphrey N J , Jakobsen B K , Price D A , Ladell K , Sewell A K
Published: December 2014

Antigen-specific T cell receptor (TCR) gene transfer via patient-derived T cells is an attractive approach to cancer therapy, with the potential to circumvent immune regulatory networks. However, high-affinity tumour-specific TCR clonotypes are typically deleted from the available repertoire during thymic selection because the vast majority of targeted epitopes are derived from autologous proteins. This process places intrinsic constraints on the efficacy of T cell-based cancer vaccines and therapeutic strategies that employ naturally generated tumour-specific TCRs. In this study, we used altered peptide ligands and lentivirus-mediated transduction of affinity-enhanced TCRs selected by phage display to study the functional properties of CD8+ T cells specific for three different tumour-associated peptide antigens across a range of binding parameters. The key findings were: (i) TCR affinity controls T cell antigen sensitivity and polyfunctionality; (ii) supraphysiological affinity thresholds exist, above which T cell function cannot be improved; and (iii) T cells transduced with very high-affinity TCRs exhibit cross-reactivity with self-derived peptides presented by the restricting human leucocyte antigen. Optimal system-defined affinity windows above the range established for natural tumour-specific TCRs therefore allow the enhancement of T cell effector function without off-target effects. These findings have major implications for the rational design of novel TCR-based biologics underpinned by rigorous preclinical evaluation.
Childhood adversity, adult homelessness and the intergenerational transmission of risk: a population‐representative study of individuals in households with children
Authors: Cutuli J. J. , Montgomery Ann Elizabeth , Evans‐Chase Michelle , Culhane Dennis P.
Published: December 2014

This study tested for associations between childhood adversity, adult homelessness and contexts of developmental risk in households with children. Data were drawn from the 2010 Washington State Behavioral Risk Factor Surveillance System, representative of the population of Washington State residents. Considering adults in households with children, those who experienced higher levels of childhood adversity were more likely to have experienced homelessness in adulthood. Meanwhile, a 10‐factor index of cumulative developmental risk was independently associated with childhood adversity and with adult homelessness. Adult homelessness appears to represent a circumstance through which past childhood adversities are brought forward and associated with contexts of developmental risk for subsequent generations of children.
Variation at presentation among colon cancer patients with metastases: a population‐based study
Authors: Heedman P. A. , Canslätt E. , Henriks G. , Starkhammar H. , Fomichov V. , Sjödahl R.
Published: December 2014

Aim

The study aimed to describe and follow a 2 year cohort of colon cancer patients with Stage IV disease from presentation to long‐term outcome.

Method

The records of 177 colon cancer patients diagnosed in southeast Sweden during 2009–2010 with disseminated disease at presentation were reviewed retrospectively.

Results

The patients were heterogeneous with respect to age, performance status and survival. Despite metastatic disease, local symptoms from the primary tumour dominated the initial clinical picture. Forty‐one per cent had anaemia. The time from suspicion of colon cancer to established diagnosis of disseminated disease varied from 0 to 231 days (emergency cases included, median 12 days). The majority (77%) were diagnosed in hospital. In 53% the primary tumour and the metastases were not diagnosed on the same occasion which may increase the risk for misinformation or delays in the care process. The possibility of simultaneous diagnosis was doubled when the patient was investigated as an inpatient. Patients were seen by one to 12 physicians (median three) in the investigation phase, and one to 47 (median 11) from diagnosis until the last record in the hospital notes. The 1‐year survival was 46%.

Conclusion

Patients with metastatic colon cancer at presentation are heterogeneous and warrant an adapted multidisciplinary approach to achieve the goal of individualized treatment for each patient in accordance with the Swedish national cancer strategy.
Transanal minimal invasive surgery for rectal lesions: should the defect be closed?
Authors: Hahnloser D. , Cantero R. , Salgado G. , Dindo D. , Rega D. , Delrio P.
Published: December 2014

Aim

Transanal minimal invasive surgery (TAMIS) of rectal lesions is increasingly being used, but the technique is not yet standardized. The aims of this study were to evaluate peri‐operative complications and long‐term functional outcome of the technique and to analyse whether or not the rectal defect needs to be closed.

Method

Consecutive patients undergoing TAMIS using the SILS port (Covidien) and standard laparoscopic instruments were studied.

Results

Seventy‐five patients (68% male) of mean age 67 (± 15) years underwent single‐port transanal surgery at three different centres for 37 benign lesions and 38 low‐risk cancers located at a mean of 6.4 ± 2.3 cm from the anal verge. The median operating time was 77 (25−245) min including a median time for resection of 36 (15−75) min and for closure of the rectal defect of 38 (9−105) min. The defect was closed in 53% using interrupted (75%) or a running suture (25%). Intra‐operative complications occurred in six (8%) patients and postoperative morbidity was 19% with only one patient requiring reoperation for Grade IIIb local infection. There was no difference in the incidence of complications whether the rectal defect was closed or left open. Patients were discharged after 3.4 (1−21) days. At a median follow‐up of 12.8 (2−29) months, the continence was normal (Vaizey score of 1.5; 0−16).

Conclusion

Transanal rectal resection can be safely and efficiently performed by means of a SILS port and standard laparoscopic instruments. The rectal defect may be left open and at 1 year continence is not compromised.
Segmental vs extended colectomy in the management of hereditary nonpolyposis colorectal cancer: a systematic review and meta‐analysis
Authors: Heneghan H. M. , Martin S. T. , Winter D. C.
Published: December 2014

Aim

The optimal surgical approach to the management of colorectal cancer in the setting of hereditary nonpolyposis colorectal cancer (HNPCC) is contentious. While some advocate total colectomy, others perform segmental resection followed by regular endoscopic surveillance. This systematic review evaluates the evidence for segmental colectomy (SC) and total (extended) colectomy (TC) in the management of HNPCC.

Method

Two major databases (PubMed and Cochrane) were searched using predefined terms. All original articles, published in English, comparing the oncological outcomes of SC and TC in HNPCC patients from January 1950 to July 2013 were included.

Results

Eighty‐four studies were identified. After applying exclusion criteria, six studies involving 948 patients were included (mean age 47.4 years, 51.8% male). SC was more commonly performed than TC (n = 780; 82.3%). Mean follow‐up was 106.5 months. Metachronous high‐risk adenomas were detected more often after SC, although the difference was not statistically significant (23.4% vs 9.6%; OR 2.258, P = 0.057). Metachronous cancers occurred more frequently after SC than after TC (23.5% vs 6.8%; OR 3.679, P < 0.005). However, there was no difference in overall survival (90.7% vs 89.8% for SC and TC, respectively; P = 0.085). Only one study reported operative mortality (0% in each group), there was no report of operative morbidity or functional outcome.

Conclusion

The optimal surgical approach in the management of HNPCC remains unclear. More adenomas and cancers occur after SC than after TC but there certainly is no evidence to suggest that more radical surgery leads to improved survival.
Suboptimal surgery and omission of neoadjuvant therapy for upper rectal cancer is associated with a high risk of local recurrence
Authors: Bondeven P. , Laurberg S. , Hagemann‐Madsen R. H. , Ginnerup Pedersen B.
Published: December 2014

Aim

The aim of the present study was to estimate the risk of local recurrence in an audited cohort of patients, with a particular focus on patients with upper rectal cancer treated by partial mesorectal excision without neoadjuvant therapy.

Method

Perioperative clinical data on all patients who underwent mesorectal excision for primary adenocarcinoma of the rectum in the period from 2007 to 2010 were prospectively collected and follow‐up data on oncological outcome were retrieved from patient records. Three‐year actuarial local recurrence rates were estimated using Kaplan–Meier methods.

Results

Local recurrence was diagnosed in 17 of 247 patients treated with curative intent. The 3‐year actuarial local recurrence rate was 7.0% (95% CI 4.0–11.8). The risk of local recurrence was negatively associated with tumour stage (P = 0.015), an involved circumferential resection margin (P = 0.007) and tumour height (P = 0.044). The local recurrence rate at 3 years was 13.5% after partial mesorectal excision, 2.9% following total mesorectal excision and 5.7% after extralevator abdominoperineal excision (P = 0.032).

Conclusion

Tumour stage and an involved circumferential resection margin were the most important predictors of local recurrence. For cancer of the upper rectum, partial mesorectal excision was associated with a high risk of local recurrence.
Assessment of the quality of patient‐orientated internet information on surgery for ulcerative colitis
Authors: Sacchi M. , Yeung T. M. , Spinelli A. , Mortensen N. J.
Published: December 2014

Aim

This study examines the quality of websites providing information on ulcerative colitis, including treatment options and surgery.

Method

Two search engines (Google and Yahoo) and the search term ‘surgery for ulcerative colitis’ were used. The first 50 sites obtained with each search engine were assessed. Sites were evaluated for content and scored using the DISCERN instrument, which evaluates the quality of health information on treatment choices.

Results

One hundred sites were examined, of which 14 were duplicates. Of the remainder, 58 provided patient‐orientated information for adults and one site provided information for surgery in children. The other 27 sites included six scientific articles, three blogs, three links, six resources for clinicians, five fora, two video links and two dead links. Of the 58 websites that provided patient information for adults, only 26 (44.8%) had been updated within the last 2 years. Only 13/58 (22.4%) were affiliated to hospitals and clinics. Most sites (38/58, 65.5%) were associated with private companies with commercial interests. Although most websites contained information on symptoms and treatment options for ulcerative colitis, 37 (63.8%) did not describe any of the risks of surgery. Overall, only seven (12.1%) websites were identified as being ‘good’ or ‘excellent’ using the DISCERN criteria.

Conclusion

The quality of patient information on surgery for ulcerative colitis is highly variable. There is potential for internet provision of valuable information and clinicians should guide patients with to access high‐quality websites.
Quantitatively Representing Nonlinear Disaster Recovery
Authors: Zobel Christopher W.
Published: December 2014

This article provides a new technique for quantitatively characterizing the progress of recovery operations in the aftermath of a disaster event. The approach extends previous research on measuring dynamic, or adaptive, disaster resilience by developing a robust approach for characterizing nonlinear disaster recovery. In doing so, it enables a more accurate mathematical representation of diﬀerent categories of recovery behavior and provides support for a much broader application of existing theory. Because the new approach inherits the ability to compare the relative behavior of multiple scenarios simultaneously, it also can serve as the basis for analytically comparing the expected performance of different plans for recovery operations. Practical application of the technique is demonstrated and discussed in the context of recovering electrical power after Hurricane Sandy struck the New York metropolitan area.
Coping with Group Behaviors in Uncertain Quality Function Deployment
Authors: Yan Hong‐Bin , Ma Tieju , Huynh Van‐Nam
Published: December 2014

Quality function deployment (QFD) is a planning and problem‐solving tool gaining wide acceptance for translating customer needs (CNs) into technical attributes (TAs) of a product. It is a crucial step to derive the prioritization of TAs from CNs in QFD. However, it is not so straightforward to prioritize TAs due to two types of uncertainties: human subjective perception and user variability. The main focus of this article is to propose a group decision‐making approach to uncertain QFD with an application to a flexible manufacturing system design. The proposed approach performs computations solely based on the order‐based semantics of linguistic labels to eliminate the burden of quantifying qualitative concepts in QFD. Moreover, it incorporates the importance weights of users and the concept of fuzzy majority into aggregations of individual fuzzy preference relations of different TAs in order to model the group behaviors in QFD. Finally, based on a quantifier‐guided net flow score procedure, the proposed approach derives a priority ranking with a classification of TAs into important and unimportant ones so as to provide a better decision‐support to the decision‐maker. Due to the easiness in articulating preferential information, our approach can reduce the cognitive burden of QFD planning team and give a practical convenience in the process of QFD planning.
Decoding Ci: From partial degradation to inhibition
Authors: Xiong Yue , Liu Chunying , Zhao Yun
Published: December 2014

Hedgehog is a morphogen, which is widely involved in the regulation of cell proliferation, differentiation and tissue patterning during development in both vertebrate and invertebrate, such as in coordination of eye, brain, gonad, gut and tracheal development. In invertebrate, Cubitus interruptus (Ci) modification process is the last identified step before transcriptional activation in the Hh signaling pathway. Ci can form a truncated repressor (CiR/Ci75) or act as an activator (CiA/Ci155) based on Hh gradient to regulate the expressions of target genes. The activity of Ci is mediated by different mechanisms, including processing, trafficking and degradation. While in vertebrate, Glioblastomas (Glis), homologs of Ci, play similar but more complex roles in the regulation of mammals Hh pathway. Hh signaling is responsible for a wide variety of processes during embryonic development and adult tissue homeostasis. Malfunction of Hh signaling could cause various diseases including birth defects and cancers. Enormous efforts were made in the past decades to explore the Hh pathway regulation and the results have provided us important insights into disease diagnosis and therapeutic treatment. In this review, we focus on a small branch of Hh pathway regulation based on studies in the Drosophila system, mainly about Ci degradation, aiming to explain how Ci is modified by different ubiquitin ligases due to the strong or moderate Hh signals and then been subjected to complete or partial degradation by proteasomes. Overall, we intend to offer an overview on how Ci responds to and relays Hh signals in a precise manner to control target genes expressions and ensures proper Hh signal transduction.
A Rare Variant of Type I Truncus Arteriosus: Truncus Arteriosus with Anterior Origin of a Main Pulmonary Artery
Authors: Çelik Serkan F. , Karakurt Cemşit , Elkıran Özlem , Öztürk Mehmet , Görmeli Ayşe C
Published: December 2014

Mini‐Abstract

Truncus arteriosus with anterior origin of a main pulmonary artery is a very rare condition. In this report we present a newborn who has a truncus arteriosus with anterior origin of a main pulmonary artery.