bluuebunny/crossref_metadata_2025 huggingface dataset:
The 5q deletion size in myeloid malignancies is correlated to additional chromosomal aberrations and to TP53 mutations
Authors: Stengel Anna , Kern Wolfgang , Haferlach Torsten , Meggendorfer Manja , Haferlach Claudia
Published: May 2016

Deletions in the long arm of chromosome 5 (del(5q)) are recurrent abnormalities in myeloid malignancies. We analyzed del(5q) and accompanying molecular mutations in MDS, MPN and MDS/MPN cases. A high del(5q) frequency was revealed in MDS (1869/11398 cases; 16%), followed by MDS/MPN (37/1107; 3%) and MPN (97/6373; 2%). To investigate potential associations of the del(5q) size with the respective phenotypes, we applied array CGH analyses in selected cohorts of 61 MDS, 22 MDS/MPN and 23 MPN cases. The size varied between 16 and 119 Mb with no differences between the entities. However, MPN and MDS/MPN cases with del(5q) sole showed a significantly smaller del(5q) than cases with additional aberrations. Sequence analysis of 27 genes revealed ≥1 mutation in 91% of patients. The highest mutation frequencies in the total cohort were observed for TP53 (31%), JAK2 (23%) and DNMT3A (18%). The molecular mutation patterns in the del(5q) cohorts were different between the entities but resembled known patterns of cohorts not selected for del(5q). Further, TP53 mutations were significantly more frequent in cases with a larger deletion size (P = 0.003). The results suggest a correlation of large del(5q) with TP53 mutations and with additional chromosomal aberrations possibly contributing to more severe courses of these cases. © 2016 Wiley Periodicals, Inc.
Copy number changes of clinically actionable genes in melanoma, non‐small cell lung cancer and colorectal cancer—A survey across 822 routine diagnostic cases
Authors: Pfarr Nicole , Penzel Roland , Klauschen Frederick , Heim Daniel , Brandt Regine , Kazdal Daniel , Jesinghaus Moritz , Herpel Esther , Schirmacher Peter , Warth Arne , Weichert Wilko , Endris Volker , Stenzinger Albrecht
Published: May 2016

Targeted deep massive parallel sequencing has been implemented in routine molecular diagnostics for high‐throughput genetic profiling of formalin‐fixed paraffin‐embedded (FFPE) cancer samples. This approach is widely used to interrogate simple somatic mutations but experience with the analysis of copy number variations (CNV) is limited. Here, we retrospectively analyzed CNV in 822 cancer cases (135 melanoma, 468 non‐small cell lung cancers (NSCLC), 219 colorectal cancers (CRC)). We observed a decreasing frequency of CNV in clinically actionable genes from melanoma to NSCLC to CRC. The overall cohort displayed 168 (20%) amplifications in 17 druggable targets. The majority of BRAF mutant melanomas (54%) showed co‐occurring CNV in other genes, mainly affecting CDKN2A. Subsets showed clustered deletions in ABL1, NOTCH1, RET or STK11, GNA11, and JAK3. Most NRAS mutant melanomas (49%) harbored CNVs in other genes with CDKN2A and FGFR3 being most frequently affected. Five BRAF/NRASwt tumors had co‐amplifications of KDR, KIT, PDGFRA and another six mutated KIT. Among all NSCLC, we identified 14 EGFRamp (with ten EGFRmut) and eight KRASamp (with seven KRASmut). KRASmut tumors displayed frequent amplifications of MYC (n = 10) and MDM2 (n = 5). Fifteen KRAS/EGFR/BRAFwt tumors had MET mutations/amplifications. In CRC, amplified IGF2 was most prevalent (n = 13) followed by MYC (n = 9). Two cases showed amplified KRAS wildtype alleles. Two of the KRASmut cases harbored amplifications of NRAS and three KRASwt cases amplification of EGFR. In conclusion, we demonstrate that our approach i) facilitates detection of CNV, ii) enables detection of known CNV patterns, and iii) uncovers new CNV of clinically actionable genes in FFPE tissue samples across cancers. © 2016 Wiley Periodicals, Inc.
Sovereign Credit Ratings in Developing Economies: New Empirical Assessment
Authors: Montes Gabriel Caldas , de Oliveira Diego S. P. , de Mendonça Helder Ferreira
Published: May 2016

This study contributes to understanding the main determinants of sovereign ratings for developing countries making use of information from Standard & Poor's, Moody's, and Fitch. Based on a sample of 40 countries for the period 1994 to 2013 and panel data approach, we extended previous works in the literature by including new economic aspects, as well as, new institutional and governance variables (e.g. inflation targeting, financial openness, democracy, corruption, etc.). The findings denote that, besides the traditional macroeconomic variables, adoption of inflation targeting, financial openness, democracy, law and order, and less corruption are important to improve the sovereign ratings. Copyright © 2016 John Wiley & Sons, Ltd.
Stem cell homing using local delivery of plerixafor and stromal derived growth factor‐1alpha for improved bone regeneration around Ti‐implants
Authors: Karlsson Johan , Harmankaya Necati , Palmquist Anders , Atefyekta Saba , Omar Omar , Tengvall Pentti , Andersson Martin
Published: May 2016

Triggering of the early healing events, including the recruitment of progenitor cells, has been suggested to promote bone regeneration. In implantology, local drug release technologies could provide an attractive approach to promote tissue regeneration. In this study, we targeted the chemotactic SDF‐1α/CXCR4 axis that is responsible e.g. for the homing of stem cells to trauma sites. This was achieved by local delivery of plerixafor, an antagonist to CXCR4, and/or SDF‐1α, from titanium implants coated with mesoporous titania thin films with a pore size of 7.5 nm. In vitro drug delivery experiments demonstrated that the mesoporous coating provided a high drug loading capacity and controlled release. The subsequent in vivo study in rat tibia showed beneficial effects with respect to bone‐implant anchorage and bone‐formation along the surface of the implants when plerixafor and SDF‐1α were delivered locally. The effect was most prominent by the finding that the combination of the drugs significantly improved the mechanical bone anchorage. These observations suggest that titanium implants with local delivery of drugs for enhanced local recruitment of progenitor cells have the ability to promote osseointegration. This approach may provide a potential strategy for the development of novel implant treatments. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2466–2475, 2016.
The Semaphorin 4D-RhoA-Akt Signal Cascade Regulates Enamel Matrix Secretion in Coordination With Cell Polarization During Ameloblast Differentiation
Authors: Otsu Keishi , Ida-Yonemochi Hiroko , Fujiwara Naoki , Harada Hidemitsu
Published: May 2016

During tooth development, oral epithelial cells differentiate into ameloblasts in order to form the most mineralized tissue in the vertebrate body: enamel. During this process, ameloblasts directionally secrete enamel matrix proteins and morphologically change from low columnar cells to polarized tall columnar cells, both of which are essential for the proper formation of enamel. In this study, we elucidated the molecular mechanism that integrates ameloblast function and morphology. Immunohistochemistry revealed that the restricted expression of semaphorin 4D (Sema4D) and RhoA activation status are closely associated with ameloblast differentiation in mouse incisors. In addition, in vitro gain-of-function and loss-of-function experiments demonstrated that Sema4D acts upstream of RhoA to regulate cell polarity and amelogenin expression via the Plexin B1/Leukemia-associated RhoGEF (LARG) complex during ameloblast differentiation. Experiments in transgenic mice demonstrated that expression of a dominant-negative form of RhoA in dental epithelium hindered ameloblast differentiation and subsequent enamel formation, as well as perturbing the establishment of polarized cell morphology and vectorial amelogenin expression. Finally, we showed that spatially restricted Akt mediates between Sema4D–RhoA signaling and these downstream cellular events. Collectively, our results reveal a novel signaling network, the Sema4D–RhoA–Akt signal cascade, that coordinates cellular function and morphology and highlights the importance of specific spatiotemporally restricted components of a signaling pathway in the regulation of ameloblast differentiation. © 2016 American Society for Bone and Mineral Research.
Ontogenetic allometry constrains cranial shape of the head‐first burrowing worm lizard Cynisca leucura (Squamata: Amphisbaenidae)
Authors: Hipsley Christy A. , Rentinck Marc‐Nicolas , Rödel Mark‐Oliver , Müller Johannes
Published: May 2016

Amphisbaenians are fossorial, predominantly limbless squamate reptiles with distinct cranial shapes corresponding to specific burrowing behaviors. Due to their cryptic lifestyles and the scarcity of museum specimens, little is known of their intraspecific variation, particularly regarding cranial osteology. This represents a critical lack of information, because the majority of morphological investigations of squamate relationships are based on cranial characters. We investigated cranial variation in the West African Coast Worm Lizard Cynisca leucura, a round‐headed member of the Amphisbaenidae. Using geometric morphometric analyses of three‐dimensional computed tomographic scans, we found that cranial osteology of C. leucura is highly conserved, with the majority of shape changes occurring during growth as the cranium becomes more slender and elongate, accompanied by increasing interdigitation among the dermal roofing bones. Elements of the ventral portion of the cranium remain loosely connected in adults, possibly as a protective mechanism against repeated compression and torsion during burrow excavation. Intraspecific variation was strongly correlated with size change from juveniles to adults, indicating a dominant role of ontogenetic allometry in determining cranial shape. We found no evidence of sexual dimorphism, either during growth or among adults. Given the fossorial habits of C. leucura, we hypothesize that cranial allometry is under strong stabilizing selection to maintain adequate proportions for head‐first digging, thereby constraining the ability of individuals to respond to differing selection pressures, including sexual selection and variation in diet or microhabitat. For species in which digging imposes less mechanical stress (e.g., in softer sand), allometric associations during growth may be weakened, allowing changes to the ontogenetic trajectory and subsequent morphological traits. Such developmental dissociation between size and shape, known as heterochrony, may also be implicit in the evolution of the other amphisbaenian cranial shapes (shovel, spade, and keel), which may themselves be functionally adapted for their respective burrowing techniques. J. Morphol. 277:1159–1167, 2016. © 2016 Wiley Periodicals, Inc.
Zika virus update II: Recent development of animal models—Proofs of association with human pathogenesis
Authors: Ramos da Silva Suzane , Gao Shou‐Jiang
Published: May 2016

Three recent studies in pregnant mice and one ongoing study in rhesus macaques evaluating the effect of ZIKV infection have provided important information about maternal‐fetus transmission and ZIKV‐related pathogenesis, confirming a causal role of ZIKV in neurological problems observed in humans. Here, we present an update of these works published in the past few weeks. J. Med. Virol. 88:1657–1658, 2016. © 2016 Wiley Periodicals, Inc.
Can cross‐talk occur in human myelinated nerve fibers?
Authors: McComas Alan
Published: May 2016

Introduction: The possibility that impulse cross‐talk can occur between myelinated human nerve fibers was explored. Methods: Instances of impulse conduction without decrement were found, and published recordings of compound action potentials of functionally homogeneous fibers were scrutinized. Results: Both analytical approaches yielded results consistent with cross‐talk occurring in some nerves after electrical stimulation. Conclusions: The possible ionic current paths in and out of neighboring fibers, which could be responsible for the phenomenon, have been considered in the light of seminal work on unmyelinated single axons. Muscle Nerve 54: 361–365, 2016
Idiopathic pulmonary fibrosis fibroblasts become resistant to Fas ligand‐dependent apoptosis via the alteration of decoy receptor 3
Authors: Im Jintaek , Kim Kyutae , Hergert Polla , Nho Richard Seonghun
Published: May 2016

Idiopathic pulmonary fibrosis (IPF) is an irreversible lethal lung disease with an unknown etiology. IPF patients' lung fibroblasts express inappropriately high Akt activity, protecting them in response to an apoptosis‐inducing type I collagen matrix. FasL, a ligand for Fas, is known to be increased in the lung tissues of patients with IPF, implicated with the progression of IPF. Expression of Decoy Receptor3 (DcR3), which binds to FasL, thereby subsequently suppressing the FasL–Fas‐dependent apoptotic pathway, is frequently altered in various human disease. However, the role of DcR3 in IPF fibroblasts in regulating their viability has not been examined. We found that enhanced DcR3 expression exists in the majority of IPF fibroblasts on collagen matrices, resulting in the protection of IPF fibroblasts from FasL‐induced apoptosis. Abnormally high Akt activity suppresses GSK‐3β function, thereby accumulating the nuclear factor of activated T‐cells cytoplasmic 1 (NFATc1) in the nucleus, increasing DcR3 expression in IPF fibroblasts. This alteration protects IPF cells from FasL‐induced apoptosis on collagen. However, the inhibition of Akt or NFATc1 decreases DcR3 mRNA and protein levels, which sensitizes IPF fibroblasts to FasL‐mediated apoptosis. Furthermore, enhanced DcR3 and NFATc1 expression is mainly present in myofibroblasts in the fibroblastic foci of lung tissues derived from IPF patients. Our results showed that when IPF cells interact with collagen matrix, aberrantly activated Akt increases DcR3 expression via GSK‐3β–NFATc1 and protects IPF cells from the FasL‐dependent apoptotic pathway. These findings suggest that the inhibition of DcR3 function may be an effective approach for sensitizing IPF fibroblasts in response to FasL, limiting the progression of lung fibrosis. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Benzolamide improves oxygenation and reduces acute mountain sickness during a high‐altitude trek and has fewer side effects than acetazolamide at sea level
Authors: Collier David J. , Wolff Chris B. , Hedges Anne‐Marie , Nathan John , Flower Rod J. , Milledge James S. , Swenson Erik R.
Published: May 2016

Acetazolamide is the standard carbonic anhydrase (CA) inhibitor used for acute mountain sickness (AMS), however some of its undesirable effects are related to intracellular penetrance into many tissues, including across the blood–brain barrier. Benzolamide is a much more hydrophilic inhibitor, which nonetheless retains a strong renal action to engender a metabolic acidosis and ventilatory stimulus that improves oxygenation at high altitude and reduces AMS. We tested the effectiveness of benzolamide versus placebo in a first field study of the drug as prophylaxis for AMS during an ascent to the Everest Base Camp (5340 m). In two other studies performed at sea level to test side effect differences between acetazolamide and benzolamide, we assessed physiological actions and psychomotor side effects of two doses of acetazolamide (250 and 1000 mg) in one group of healthy subjects and in another group compared acetazolamide (500 mg), benzolamide (200 mg) and lorazepam (2 mg) as an active comparator for central nervous system (CNS) effects. At high altitude, benzolamide‐treated subjects maintained better arterial oxygenation at all altitudes (3–6% higher at all altitudes above 4200 m) than placebo‐treated subjects and reduced AMS severity by roughly 50%. We found benzolamide had fewer side effects, some of which are symptoms of AMS, than any of the acetazolamide doses in Studies 1 and 2, but equal physiological effects on renal function. The psychomotor side effects of acetazolamide were dose dependent. We conclude that benzolamide is very effective for AMS prophylaxis. With its lesser CNS effects, benzolamide may be superior to acetazolamide, in part, because some of the side effects of acetazolamide may contribute to and be mistaken for AMS.
A randomized, crossover pharmacodynamic study of immediate‐release omeprazole/sodium bicarbonate and delayed‐release lansoprazole in healthy adult volunteers
Authors: Pratha Vijayalakshmi S. , McGraw Thomas , Tobin William
Published: May 2016

Proton pump inhibitors (PPIs) effectively block gastric acid secretion and are the treatment of choice for heartburn. PPIs differ, however, in onset of action and bioavailability. In this single‐center, open‐label, three‐way crossover study, onset of action of immediate‐release omeprazole 20 mg/sodium bicarbonate 1100 mg (IR‐OME) and delayed‐release (DR) lansoprazole 15 mg was evaluated in 63 healthy fasting adults. Subjects were randomized to once daily IR‐OME, or DR‐lansoprazole, or no treatment for 7 days. The primary efficacy endpoint was the earliest time where a statistically significant difference was observed between IR‐OME and DR‐lansoprazole in median intragastric pH scores for three consecutive 5‐min intervals on day 7. Secondary endpoints compared effects of active treatments on days 1 and 7 (e.g., time to sustained inhibition, percentage of time with pH >4). A significant difference in median intragastric pH favoring IR‐OME was observed on day 7 starting at the 10‐ to 15‐min interval postdosing (P = 0.024) and sustaining through the 115‐ to 120‐min interval (P = 0.017). On day 1, IR‐OME achieved sustained inhibition of intragastric acidity significantly faster than DR‐lansoprazole. IR‐OME maintained pH >4 significantly longer than DR‐lansoprazole over a 24‐h period (P = 0.007) on day 7. Overall, results of this study demonstrate IR‐OME is safe and well tolerated and that treatment with IR‐OME results in significantly faster onset of action and better gastric acid suppression at steady state than DR‐lansoprazole.
Phthalimide‐derived strigolactone mimics as germinating agents for seeds of parasitic weeds
Authors: Cala Antonio , Ghooray Kala , Fernández‐Aparicio Mónica , Molinillo José MG , Galindo Juan CG , Rubiales Diego , Macías Francisco A
Published: May 2016

BACKGROUND

Broomrapes attack important crops, cause severe yield losses and are difficult to eliminate because their seed bank is virtually indestructible. In the absence of a host, the induction of seed germination leads to inevitable death due to nutrient starvation. Synthetic analogues of germination‐inducing factors may constitute a cheap and feasible strategy to control the seed bank. These compounds should be easy and cheap to synthesise, as this will allow their mass production. The aim of this work is to obtain new synthethic germinating agents.

RESULTS

Nineteen N‐substituted phthalimides containing a butenolide ring and different substituents in the aromatic ring were synthesised. The synthesis started with commercially available phthalimides. The complete collection was assayed against the parasitic weeds Orobanche minor, O. cumana, Phelipanche ramosa and P. aegyptiaca, with the synthetic strigolactone analogue GR24 used as a positive control. These compounds offered low EC50 values: O. cumana 38.3 μM, O. minor 3.77 μM, P. aegyptiaca 1.35 μM and P. ramosa 1.49 μM.

CONCLUSIONS

The synthesis was carried out in a few steps and provided the target compounds in good yields. The compounds tested showed great selectivity, and low EC50 values were obtained for structures that were simpler than GR24. © 2016 Society of Chemical Industry
Influence of nanochannels on Poisson's ratio of degenerate crystal of hard dimers
Authors: Narojczyk Jakub W. , Kowalik Mikołaj , Wojciechowski Krzysztof W.
Published: May 2016

Abstractauthoren Hard‐body models reproduce many fundamental features of real physical systems and are convenient tools to study the role of molecular shape and its influence on macroscopic, for example, elastic, properties of condensed matter. In this article, a degenerate (aperiodic) crystal of hard dimers with arrays of nanochannels introduced in the direction is studied by Monte Carlo simulations. The nanochannels are filled by hard spheres of diameter which can be different from the diameter of spheres forming dimers. It is shown that, by modifying the ratio , one can qualitatively modify the Poisson's ratio of the system. In particular, one can obtain partial auxetics (i.e., systems with negative Poisson's ratio in some directions) with auxetic directions or . The applied method is convenient to determine Poisson's ratio in all directions for crystals of arbitrary symmetry. Explicit formulae for Poisson's ratio in main directions of the studied structures are given.

Structure of hard dimers (green atoms) with an array of nanochannels (red atoms). Diameters of dimer atoms have been intentionally decreased to reveal underlying molecular structure (black segments) and channel orientation.
Therapeutic Potential of Polyphenols from Epilobium Angustifolium (Fireweed)
Authors: Schepetkin Igor A. , Ramstead Andrew G. , Kirpotina Liliya N. , Voyich Jovanka M. , Jutila Mark A. , Quinn Mark T.
Published: May 2016

Epilobium angustifolium is a medicinal plant used around the world in traditional medicine for the treatment of many disorders and ailments. Experimental studies have demonstrated that Epilobium extracts possess a broad range of pharmacological and therapeutic effects, including antioxidant, anti‐proliferative, anti‐inflammatory, antibacterial, and anti‐aging properties. Flavonoids and ellagitannins, such as oenothein B, are among the compounds considered to be the primary biologically active components in Epilobium extracts. In this review, we focus on the biological properties and the potential clinical usefulness of oenothein B, flavonoids, and other polyphenols derived from E. angustifolium. Understanding the biochemical properties and therapeutic effects of polyphenols present in E. angustifolium extracts will benefit further development of therapeutic treatments from this plant. Copyright © 2016 John Wiley & Sons, Ltd.
How Indian Pharmaceutical Companies Are Building Global Brands: The Case of the Himalaya Herbal Brand
Authors: Srivastava Rajesh
Published: May 2016

This study aims to understand how Indian brands are built globally. The study also gives insight on understanding the mode of entry adopted by Indian companies with special reference to the Himalaya Drug Company. The study takes a multistage approach through secondary data analysis, an interpretative approach, and interviews of 15 pharmaceutical personnel and 30 consumers from the United States through focus interviews. The interviews were recorded. It is qualitative descriptive research. Our research shows that Himalaya has used a franchising model to build their herbal brands through retail franchisees, and a problem‐solution approach strategy in communication. Emphasis on customer experience has created good word‐of‐mouth and generated good revenue for its herbal brands. Quality, effectiveness, price, and availability are the key factors for herbal brand building. The product mix is selected based on the country's culture and consumers' needs. They also capitalized on newfound Indian pride and confidence due to faster gross domestic product (GDP) growth. This article contributes to a better understanding of the opportunities and challenges associated with brands from emerging markets, in particular, India, as well as the development of brands from emerging markets, which is becoming more important at the economic and political level. It also helps to better understand mode of entry, especially for small companies. © 2016 Wiley Periodicals, Inc.
Fetal myocardial deformation in maternal diabetes mellitus and obesity
Authors: Kulkarni A. , Li L. , Craft M. , Nanda M. , Lorenzo J. M. M. , Danford D. , Kutty S.
Published: May 2016

Objective

Experimental evidence suggests that changes in the fetal myocardium result from intrauterine effects of maternal diabetes mellitus and obesity. The aim of this study was to assess fetal cardiac function using two‐dimensional speckle‐tracking echocardiography to determine the effects of maternal diabetes and obesity on the fetal myocardium.

Methods

Comparative cross‐sectional evaluation of myocardial function in fetuses of mothers with diabetes mellitus (FDM) or obesity (FO) and normal gestational age‐matched control fetuses (FC) was performed using two‐dimensional speckle‐tracking echocardiography at two centers.

Results

In total, 178 fetuses (82 FDM, 26 FO and 70 FC) met the enrolment criteria. Mean gestational age at assessment was similar among groups: 25.3 ± 5.1 weeks for FDM, 25.0 ± 4.6 weeks for FO and 25.1 ± 4.9 weeks for FC. Mean maternal body mass index was significantly higher in FDM and FO groups compared with the FC group. Statistically significant differences in fetal cardiac function were detected between FDM and FC for global longitudinal strain (mean ± SD, –21.4 ± 6.5% vs –27.0 ± 5.2%; P < 0.001), global circumferential strain (mean ± SD, –22.6 ± 6.5% vs –26.2 ± 6.8%; P = 0.002), average longitudinal systolic strain rate (median, –1.4 (interquartile range (IQR), –1.7 to –1.1)/s vs –1.6 (IQR, –2.0 to –1.4)/s; P = 0.001) and average circumferential systolic strain rate (median, –1.4 (IQR, –1.9 to –1.1)/s vs –1.6 (IQR, –2.1 to –1.3)/s; P = 0.006). Cases of non‐obese FDM also had abnormal strain parameters compared with FC. Global longitudinal strain (mean ± SD, –21.1 ± 7.5%) and average circumferential systolic strain rate (median, –1.3 (IQR, –1.8 to –1.1)/s) were significantly lower in FO compared with FC.

Conclusions

Unfavorable changes occur in the fetal myocardium in response to both maternal diabetes mellitus and obesity. The long‐term prognostic implications of these changes require further study. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
Efficacy of Prophylactic Mesh in End‐Colostomy Construction: A Systematic Review and Meta‐analysis of Randomized Controlled Trials
Authors: Wang Shuanhu , Wang Wenbin , Zhu Bing , Song Guolei , Jiang Congqiao
Published: May 2016

Background

Parastomal hernia is a very common complication after colostomy, especially end‐colostomy. It is unclear whether prophylactic placement of mesh at the time of stoma formation could prevent parastomal hernia formation after surgery for rectal cancer. A systematic review and meta‐analysis were conducted to evaluate the efficacy of prophylactic mesh in end‐colostomy construction.

Methods

PubMed, Embase, and the Cochrane Library were searched, covering records entered from their inception to September 2015. Randomized controlled trials (RCTs) comparing stoma with mesh to stoma without mesh after surgery for rectal cancer were included. The primary outcome was the incidence of parastomal hernia. Pooled risk ratios (RR) with 95 % confidence intervals (CI) were obtained using random effects models.

Results

Six RCTs containing 309 patients were included. Parastomal hernia occurred in 24.4 % (38 of 156) of patients with mesh and 50.3 % (77 of 153) of patients without mesh. Meta‐analysis showed a lower incidence of parastomal hernia (RR, 0.42; 95 % CI 0.22–0.82) and reoperation related to parastomal hernia (RR, 0.23; 95 % CI 0.06–0.89) in patients with mesh. Stoma‐related morbidity was similar between mesh group and non‐mesh group (RR, 0.65; 95 % CI 0.33–1.30).

Conclusions

Prophylactic placement of a mesh at the time of a stoma formation seems to be associated with a significant reduction in the incidence of parastomal hernia and reoperation related to parastomal hernia after surgery for rectal cancer, but not the rate of stoma‐related morbidity. However, the results should be interpreted with caution because of the heterogeneity among the studies.
Climbing the Ladder: Experience with Developing a Large Group Genetic Counselor Career Ladder at Children's National Health System
Authors: Kofman Laura , Seprish Mary Beth , Summar Marshall
Published: May 2016

Children's National Health System (CNHS) is a not‐for‐profit pediatric hospital that employs around twenty genetic counselors in a range of specialties, including clinical pediatric, neurology, fetal medicine, research, and laboratory. CNHS lacked a structured system of advancement for their genetic counselors; therefore, a formal career ladder was proposed by the genetic counselors based on years of experience, responsibility, and job performance. This career ladder utilized monetary, academic, and seniority incentives to encourage advancement and continue employment at CNHS. The creation and ultimate approval of the career ladder required direct input from genetic counselors, Department Chairs, and Human Resource personnel. The establishment of a genetic counselor career ladder at CNHS will hopefully benefit the profession of genetic counselors as a whole and allow other facilities to create and maintain their own career ladder to meet the needs of the growing, competitive, field of genetic counseling.
Changes in Retinal N‐Acylethanolamines and their Oxylipin Derivatives During the Development of Visual Impairment in a Mouse Model for Glaucoma
Authors: Montgomery Christa L. , Keereetaweep Jantana , Johnson Heather M. , Grillo Stephanie L. , Chapman Kent D. , Koulen Peter
Published: May 2016

Neurons are especially susceptible to oxidative damage, which is increasingly implicated in neurodegenerative disease. Certain N‐acylethanolamines (NAEs) have been shown to protect neurons from oxidative stress. Since glaucoma may be considered a neurodegenerative disorder and the survival of retinal neurons could also be influenced by N‐acylethanolamines, our goal was to quantify changes in certain N‐acylethanolamine species and their oxylipin derivatives in the retina of a mouse model for glaucoma. We also sought to identify relationships between these and parameters of glaucoma disease development, specifically intraocular pressure, visual acuity, and contrast sensitivity. Five N‐acylethanolamine species and three NAE oxylipin derivatives were quantified in retina from young and aged DBA/2Crl mice. N‐Acylethanolamines and NAE‐oxylipins in retinal extracts were quantified against deuterated standards by isotope dilution gas chromatography–mass spectrometry. Levels (nmol/g dry weight) of N‐arachidonoylethanolamine (anandamide; NAE 20:4) were significantly (p = 0.008) decreased in aged (2.875 ± 0.6702) compared to young animals (5.175 ± 0.971). Conversely, the anandamide oxylipin, 15(S)‐HETE ethanolamide (15(S)‐HETE EA), was significantly (p = 0.042) increased in aged (0.063 ± 0.009) compared to young animals (0.039 ± 0.011). Enzymatic depletion of the anandamide pool by 15‐lipoxygenase and consequent accumulation of 15(S)‐HETE ethanolamine may contribute to decreased visual function in glaucomatous mice. Since N‐acylethanolamines effectively attenuate glaucoma pathogenesis and associated visual impairment, our data provides additional rationale and novel targets for glaucoma therapies.
Raising awareness of cognitive biases during diagnostic reasoning
Authors: Van Geene Kaylee , De Groot Esther , Erkelens Carmen , Zwart Dorien
Published: May 2016

Introduction Bias in diagnostic reasoning can potentially lead to severe consequences. We explored how to design an experiential learning workshop in a general practice clerkship to raise awareness on bias.

Method A group of 12 students was split into two groups. Both groups ‘diagnosed’ two patients in two case studies. Only one group, without them knowing, were given a case including salient distracting features. The whole group discussed the influence of these distractors. In the second round all students had salient distracting features in their case descriptions but only one group had a debiasing tool, a checklist to reconsider their first diagnosis, which they discussed in the final large group discussion.

Results Students were misled by salient distracting features and thus experienced how one small difference in a case description may lead to a different diagnosis, due to bias. The debiasing tool was regarded with scepticism. Afterwards, students indicated that, thanks to experiencing bias themselves, they felt better equipped to recognize the risk of bias.

Conclusions An experiential learning approach with case studies containing salient distracting features seems to be a viable method to learn about bias in a general practice clerkship.
Effects of previous ovarian drilling on cumulative ongoing pregnancy rates among patients with polycystic ovarian syndrome undergoing in vitro fertilization
Authors: Cai Jiali , Liu Lanlan , Sun Lingbin , Sha Aiguo , Jiang Xiaoming , Ren Jianzhi
Published: May 2016

Objective

To determine if history of undergoing laparoscopic ovarian drilling (LOD) was associated with changes in cumulative ongoing pregnancy rates following in‐vitro fertilization in patients with polycystic ovary syndrome (PCOS).

Methods

The present retrospective study was performed in an in vitro fertilization unit in Xiamen, China, between June 1, 2008 and December 31, 2012. Patient characteristics and in vitro fertilization treatment outcomes were compared between patients with PCOS and a history of LOD (LOD group), patients with PCOS without a history of LOD (no‐LOD group), and age‐matched patients without PCOS and with no history of LOD (age‐matched group).

Results

The study included 110 patients in the LOD group, 127 patients in the no‐LOD group, and 990 patients in the age‐matched group. A lower number of retrieved oocytes, fewer available embryos, and a lower number of cryopreserved embryos were observed in among patients in the LOD‐group compared with the other groups (P ≤ 0.001). No differences in birth rates following fresh embryo transfers were observed between the LOD‐group, and the age‐matched group (P = 0.274) and the no‐LOD group (P = 0.120). A higher adjusted odds ratio of cumulative pregnancy per initiated in vitro fertilization cycle was observed in the no‐LOD group when compared with the LOD group (1.976; 95% confidence interval 1.091–3.580).

Conclusion

LOD could compromise cumulative ongoing pregnancy rates during subsequent in vitro fertilization.
Evaluating topical opioid gel on donor site pain: A small randomised double blind controlled trial
Authors: Fransén Jian , Bastami Salumeh , Sjöberg Folke , Uppugunduri Srinivas , Huss Fredrik R.M.
Published: May 2016

ABSTRACT

Background:

Autologous donor skin harvested for transplantation is a common procedure in patients with burns, and patients often feel more pain at the donor site than is justified by the extent of trauma. Topical morphine gels have been thought to have an effect on peripheral opioid receptors by creating antinociceptive and anti-inflammatory effects, which could potentially reduce the systemic use of morphine-like substances and their adverse effects.

Methods:

We therefore did a paired, randomised, double-blind placebo study to investigate the effect of morphine gel and placebo on dual donor sites that had been harvested in 13 patients. Pain was measured on a visual analogue scale (VAS) 15 times in a total of 5 days.

Results:

The mean (SD) VAS was 1.6 (2.3) for all sites, 1.5 (2.2) for morphine, and 2.0 (2.5) for placebo. The pain relieving effects of morphine gel were not significantly better than placebo.

Conclusion:

The assessment of pain at donor sites is subjective, and more systematic and objective studies are needed.

Highlights
Is Bondage and Discipline, Dominance and Submission, and Sadomasochism Recreational Leisure? A Descriptive Exploratory Investigation
Authors: Williams DJ. , Prior Emily E. , Alvarado Thea , Thomas Jeremy N. , Christensen M. Candace
Published: May 2016

Introduction

Recent studies have suggested that, in contrast to traditional psychopathologic explanations, bondage and discipline, dominance and submission, and sadomasochism (BDSM) could be understood as recreational leisure. However, the theoretical framing of BDSM as potential leisure has not been empirically explored.

Aim

To conduct an initial empirical exploration to determine whether BDSM experience fits established characteristics of recreational leisure.

Methods

A convenience sample of BDSM participants (N = 935) completed an online survey (9 demographic questions and 17 leisure questions) that assessed BDSM experience according to important attributes of leisure. Responses also were assessed and statistically compared as being primarily casual or serious leisure according to general BDSM identities (ie, dominants vs submissives vs switches).

Main Outcome Measures

BDSM experiences were assessed as a form of potential leisure.

Results

Most BDSM experiences met leisure criteria. Participants reported that “most of the time or nearly always” BDSM was associated with a sense of personal freedom (89.7% of participants), pleasure or enjoyment (98.5%), sense of adventure (90.7%), use of personal skills (90.8%), relaxation or decreased stress (91.4%), self-expression or exploration (90.6%), and positive emotions (96.6%). BDSM seemed to function as primarily serious, rather than casual, leisure, but important statistical differences were observed based on specific BDSM identities.

Conclusion

A leisure science perspective could be valuable to researchers and clinicians in reinterpreting the wide range of diverse BDSM motivations and practices.
Using optical coherence tomography to evaluate macular changes after surgical management for rhegmatogenous retinal detachment
Authors: Cheng Kai‐Chun , Cheng Kai‐Yuan , Cheng Kai‐Hung , Chen Kuo‐Jen , Chen Chia‐Hui , Wu Wen‐Chuan
Published: May 2016

Incomplete visual recovery, color vision defects, or persistent metamorphopsia may persist even after successful surgery for rhegmatogenous retinal detachment (RRD), especially in cases of RD with macula off, suggesting microstructural macular damage that standard fundus biomicroscopy could not detect. We compared spectral‐domain optical coherence tomography imaging with preoperative and postoperative visual acuity to evaluate the relationship between morphological changes in the outer retina and visual outcome after successful repair of RRD with macula on or off. We enrolled 43 patients (43 eyes) with successful repair of RRD and a minimum 6‐month follow up after surgery in this retrospective research. Patients accepted spectral‐domain optical coherence tomography postoperatively and visual acuity examination preoperatively and postoperatively. The mean age of the patients was 48.74 ± 12.68 years (range: 16–77 years). The mean visual acuity (logarithm of minimal angle of resolution) before surgery was 0.87 ± 0.70. Disrupted ellipsoid zone was noted in one of 11 eyes in the macula‐on group (9.1%) and 19 of 32 eyes in the macula‐off group (59.4%). Disrupted external limiting membrane (ELM) was noted in no eye in the macula‐on group (0%) and 11 of 32 eyes in the macula‐off group (34.4%). The macula‐off group was associated with better postoperative visual gains than the macula‐on group (p = 0.013). Patients with integrity of the ellipsoid zone and ELM were associated with significant visual improvement than patients with disruption of the ellipsoid zone or ELM.
Entropy Generation Case Studies of Two-Immiscible Fluids Under the Influence of a Uniform Magnetic Field in an Inclind Channel
Authors: Nezhad A. H. , Shahri M. F.
Published: May 2016

This paper deals with entropy generation of two immiscible fluids inside an inclined channel under the influence of a uniform magnetic field. The channel consists of two regions such that a viscous fluid occupies the region I and an electrically conducting fluid occupies the region II. The governing equations of momentum and energy for two regions are solved by Mathematica package BVPh 2.0 which is based on homotopy analysis method. The analytical results are validated against other numerical simulations and experimental data and excellent agreements are achieved. The entropy generation components due to heat transfer and fluid friction for two immiscible fluids are formulated and then the total entropy generation is computed. The influence of various parameters including Grashof number, Hartmann number and inclination angle on the total entropy generation and its components is examined and discussed. Results show that total entropy generation has a direct relationship with Grashof number and inclination angle, while it has a reverse relationship with Hartmann number. It can also be found that although the enlargement of Hartmann number increases the contribution of entropy generation due to Ohmic dissipation, it still reduces the total entropy generation inside the channel.
A model of collaboration network formation with heterogeneous skills
Authors: ANDERSON KATHARINE A.
Published: May 2016

Collaboration networks provide a method for examining the highly heterogeneous structure of collaborative communities. However, we still have limited theoretical understanding of how individual heterogeneity relates to network heterogeneity. The model presented here provides a framework linking an individual's skill set to her position in the collaboration network, and the distribution of skills in the population to the structure of the collaboration network as a whole. This model suggests that there is a non-trivial relationship between skills and network position: individuals with a useful combination of skills will have a disproportionate number of links in the network. Indeed, in some cases, an individual's degree is non-monotonic in the number of skills she has—an individual with very few skills may outperform an individual with many. Special cases of the model suggest that the degree distribution of the network will be skewed, even when the distribution of skills is uniform in the population. The degree distribution becomes more skewed as problems become more difficult, leading to a community dominated by a few high-degree superstars. This has striking implications for labor market outcomes in industries where production is largely the result of collaborative effort.
X-ray powder diffraction data for trelagliptin succinate, C18H20FN5O2•C4H6O4
Authors: Guo Liu Qi , Zheng Shou Jun , Ma Xiao Li , Li Hui
Published: May 2016

Experimental X-ray powder diffraction data, unit-cell parameters, and space group for trelagliptin succinate, C18H20FN5O2•C4H6O4, are reported [a = 18.481(6), b = 8.120(4), c = 7.903(4) Å, α = 89.972(0)°, β = 97.722(4)°, γ = 90.120(0)°, unit-cell volume V = 1175.37 Å3, Z = 2, and space-group P1]. All measured lines were indexed and are consistent with the P1 space group. No detectable impurity was observed.
Past and present dynamics of Skelton Glacier, Transantarctic Mountains
Authors: Jones R.S. , Golledge N.R. , Mackintosh A.N. , Norton K.P.
Published: May 2016

Any future changes in the volume of Antarctica’s ice sheets will depend on the dynamic response of outlet glaciers to shifts in environmental conditions. In the Transantarctic Mountains, this response is probably heavily dependent on the geometry of the system, but few studies have quantified the sensitivity of these glaciers to environmental forcings. Here we investigated the controls, along-flow sensitivity and time-dependent dynamics of Skelton Glacier. Three key outcomes were: i) present-day flow is governed primarily by surface slope, which responds to reduced valley width and large bed undulations, ii) Skelton Glacier is more susceptible to changes in atmospheric temperature than precipitation through its effect on basal sliding near the grounding line, and iii) under conditions representative of Pliocene and Quaternary climates large changes in ice thickness and velocity would have occurred in the lower reaches of the glacier. Based on these new quantitative predictions of the past and present dynamics of Skelton Glacier, we suggest that similar Transantarctic Mountain outlet glaciers could experience greater ice loss in their confined, lower reaches through increased basal sliding and ocean melt under warmer-than-present conditions. These effects are greatest where overdeepenings exist near the grounding line.
Forward Clusters for Degenerate Random Environments
Authors: HOLMES MARK , SALISBURY THOMAS S.
Published: May 2016

We consider connectivity properties and asymptotic slopes for certain random directed graphs on ℤ2in which the set of points$\mathcal{C}_o$that the origin connects to is always infinite. We obtain conditions under which the complement of$\mathcal{C}_o$has no infinite connected component. Applying these results to one of the most interesting such models leads to an improved lower bound for the critical occupation probability for oriented site percolation on the triangular lattice in two dimensions.
Preparedness of Finnish Emergency Medical Services for Chemical Emergencies
Authors: Jama Timo J. , Kuisma Markku J.
Published: May 2016

Introduction

The preparedness level of Finnish Emergency Medical Services (EMS) for treating chemical emergencies is unknown. The aim of this study was to survey the preparedness level of EMS systems for managing and handling mass-casualty chemical incidents in the prehospital phase in Finland.

Hypothesis

The study hypothesis was that university hospital districts would have better clinical capability to treat patients than would central hospital districts in terms of the number of patients treated in the field within one hour after dispatching as well as patients transported to hospital within one hour or two hours after dispatching.

Methods

This cross-sectional study was conducted as a Webropol (Wuppertal, Germany) survey. All hospital districts (n=20) in continental Finland were asked about their EMS preparedness level in terms of capability of treating and transporting chemically affected patients in the field. Their capability for decontamination of affected patients in the field was also inquired.

Results

University hospital district-based EMS systems had at least 20% better absolute clinical capacity than central hospital-based EMS systems for treating chemically affected patients concerning all treatments inquired about, except the capacity for non-invasive ventilation (NIV)/continuous positive airway pressure (CPAP) treatment in the field. Overall, there was a good level of preparedness for treating chemical accident patients with supplemental oxygen, bronchodilators, and inhaled corticosteroids. Preparedness for providing antidote therapy in cases of cyanide gas exposure was, in general, low. The variation among the hospital districts was remarkable. Only nine of 15 central hospital district EMS had a mobile decontamination unit available, whereas four of five university hospital districts had one.

Conclusion

Emergency Medical Services capacity in Finland for treating chemically affected patients in the field needs to be improved, especially in terms of antidote therapy. Mobile decontamination units should be available in all hospital districts.

JamaTJ, KuismaMJ. Preparedness of Finnish Emergency Medical Services for chemical emergencies. Prehosp Disaster Med. 2016;31(4):392–396.
The Promise of Direct-to-Consumer Telehealth for Disaster Response and Recovery
Authors: Uscher-Pines Lori , Fischer Shira , Chari Ramya
Published: May 2016

Telehealth has great promise to improve and even revolutionize emergency response and recovery. Yet telehealth in general, and direct-to-consumer (DTC) telehealth in particular, are underutilized in disasters. Direct-to-consumer telehealth services allow patients to request virtual visits with health care providers, in real-time, via phone or video conferencing (online video or mobile phone applications). Although DTC services for routine primary care are growing rapidly, there is no published literature on the potential application of DTC telehealth to disaster response and recovery because these services are so new. This report presents several potential uses of DTC telehealth across multiple disaster phases (acute response, subacute response, and recovery) while noting the logistical, legal, and policy challenges that must be addressed to allow for expanded use.

Uscher-PinesL,FischerS,ChariR.The promise of direct-to-consumer telehealth for disaster response and recovery.Prehosp Disaster Med.2016;31(4):454–456.