bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic review of the association of venous oxygenation and outcome in adult hospitalized patients
Authors: Chemtob R. A. , Eskesen T. G. , Moeller‐Soerensen H. , Perner A. , Ravn H. B.
Published: September 2016

Background

Adequate tissue oxygenation is necessary to maintain organ function. Low venous oxygen saturation may reflect impaired tissue oxygenation, and may be used as a predictive tool and a therapeutic target to improve the care of critically ill patients. We therefore conducted a systematic review of the existing literature reflecting these aspects.

Methods

We searched electronic databases in January 2016 for relevant studies on venous oxygen saturation for treatment guidance and patient outcome. We sub‐grouped results based on patient groups and setting.

Results

The search resulted in 5590 papers of which 42 studies were deemed relevant. The majority of the studies in cardiac and abdominal surgery patients showed associations between low venous oxygen saturation and increased mortality and morbidity, in particular increased length of intensive care. However, the cut‐off level for low venous oxygen saturation varied between < 55 and 70% and all studies had high risk of bias. In patients with septic shock, recent randomized trials showed no benefit of early resuscitation guided by venous oxygen saturation.

Conclusion

Low venous oxygen saturation may be associated with increased mortality, morbidity and length of intensive care in patients following cardiac or abdominal surgery. However, the wide range of cut‐off levels and low quality of evidence hampers the clinical application. In patients with septic shock, the present evidence does not support goal‐directed therapy using venous oxygen saturation during early resuscitation.
Evidence of positive selection and concerted evolution in the rapidly evolving PRDM9 zinc finger domain in goats and sheep
Authors: Ahlawat S. , Sharma P. , Sharma R. , Arora R. , Verma N. K. , Brahma B. , Mishra P. , De S.
Published: September 2016

Meiotic recombination contributes to augmentation of genetic diversity, exclusion of deleterious alleles and proper segregation of chromatids. PRDM9 has been identified as the gene responsible for specifying the location of recombination hotspots during meiosis and is also the only known vertebrate gene associated with reproductive isolation between species. PRDM9 encodes a protein with a highly variable zinc finger (ZF) domain that varies between as well as within species. In the present study, the ZF domain of PRDM9 on chromosome 1 was characterized for the first time in 15 goat breeds and 25 sheep breeds of India. A remarkable variation in the number and sequence of ZF domains was observed. The number of ZF repeats in the ZF array varied from eight to 12 yielding five homozygous and 10 heterozygous genotypes. The number of different ZF domains was 84 and 52 producing 36 and 26 unique alleles in goats and sheep respectively. The posterior mean of dN/dS or omega values were calculated using the codeml tool of pamlx to identify amino acids that are evolving positively in goats and sheep, as positions −1, +3 and +6 in the ZF domain have been reported to experience strong positive selection across different lineages. Our study identified sites −5, −1, +3, +4 and +6 to be experiencing positive selection. Small ruminant zinc fingers were also found to be evolving under concerted evolution. Our results demonstrate the existence of a vast diversity of PRDM9 in goats and sheep, which is in concert with reports in many metazoans.
Predicting and Interpolating State‐Level Polls Using Twitter Textual Data
Authors: Beauchamp Nicholas
Published: September 2016

Spatially or temporally dense polling remains both difficult and expensive using existing survey methods. In response, there have been increasing efforts to approximate various survey measures using social media, but most of these approaches remain methodologically flawed. To remedy these flaws, this article combines 1,200 state‐level polls during the 2012 presidential campaign with over 100 million state‐located political tweets; models the polls as a function of the Twitter text using a new linear regularization feature‐selection method; and shows via out‐of‐sample testing that when properly modeled, the Twitter‐based measures track and to some degree predict opinion polls, and can be extended to unpolled states and potentially substate regions and subday timescales. An examination of the most predictive textual features reveals the topics and events associated with opinion shifts, sheds light on more general theories of partisan difference in attention and information processing, and may be of use for real‐time campaign strategy.
Clinical risk scores in the current era of neoadjuvant chemotherapy for colorectal liver metastases
Authors: Kumar Rohan , Dennison Ashley R. , Robertson Vaux , Jones Michael J. , Neal Christopher P. , Garcea Giuseppe
Published: September 2016

Background

Clinical risk scores (CRS) within the context of neoadjuvant chemotherapy for colorectal liver metastases (CRLM) has not been validated. The predictive value of clinical risk scoring in patients administered neoadjuvant chemotherapy prior to liver surgery for CRLM is evaluated.

Methods

A prospective database over a 15‐year period (April 1999 to March 2014) was analysed. We identified two groups: A, neoadjuvant chemotherapy prior to CRLM surgery; and B, no neoadjuvant chemotherapy.

Results

Overall median survival in groups A and B were 36 (2–137) months and 33 (2–137) months. In group A, nodal status, size, number of metastases and carcinoembryonic antigen levels were not found to be independent predictors of overall survival (OS). However, patients with a shorter disease‐free interval of less than 12 months had an increased OS (P = 0.0001). Multivariate analysis of high‐ and low‐risk scores compared against survival in group B (P < 0.05) confirms the applicability of the scoring system in traditional settings.

Conclusion

Traditional CRS are not a prognostic predictive tool when applied to patients receiving neoadjuvant chemotherapy for CRLM. Disease‐free interval may be one independent variable for use in future risk score systems specifically developed for the neoadjuvant chemotherapy era.
Prevalence of non‐union and delayed union in proximal humeral fractures
Authors: Papakonstantinou Maritsa K. , Hart Melissa J. , Farrugia Richard , Gosling Cameron , Kamali Moaveni Afshin , van Bavel Dirk , Page Richard S. , Richardson Martin D.
Published: September 2016

Background

Little is known about the prevalence of proximal humeral non‐union. There is disagreement on what constitutes union, delayed union and non‐union. Our aim was to determine the prevalence of these complications in proximal humeral fractures (PHFs) admitted to trauma hospitals.

Methods

The Victorian Orthopaedic Trauma Outcomes Registry identified 419 cases of PHFs, of which 306 were analysed. Three upper limb orthopaedic surgeons used X‐rays to classify fractures according to the Neer classification and determine union. Twelve‐item Short Form Health Survey scores were used to assess patient health and wellbeing.

Results

Of 306 cases, 49.4% reached union. Median time to union was 100 days (confidence interval 90–121). Of these, 17.0% united by 60 days, 8.5% united by 89 days and 23.9% united after 90 days, demonstrating ‘prolonged delayed union’. There were 25 non‐unions with a prevalence of 8.2%, most occurring in two‐part surgical neck fractures.

Conclusion

Our cohort of largely displaced PHFs admitted to trauma hospitals had a non‐union prevalence of 8.2% and an overall delayed union prevalence of 32.4%. Consensus is required on definitions of non‐union and delayed union timeframes.
Microtubule destabilising agents: far more than just antimitotic anticancer drugs
Authors: Bates Darcy , Eastman Alan
Published: September 2016

Vinca alkaloids have been approved as anticancer drugs for more than 50 years. They have been classified as cytotoxic chemotherapy drugs that act during cellular mitosis, enabling them to target fast growing cancer cells. With the evolution of cancer drug development there has been a shift towards new “targeted” therapies to avoid the side effects and general toxicities of “cytotoxic chemotherapies” such as the vinca alkaloids. Due to their original classification, many have overlooked the fact that vinca alkaloids, taxanes and related drugs do have a specific molecular target: tubulin. They continue to be some of the most effective anticancer drugs, perhaps because their actions upon the microtubule network extend far beyond the ability to halt cells in mitosis, and include the induction of apoptosis at all phases of the cell cycle. In this review, we highlight the numerous cellular consequences of disrupting microtubule dynamics, expanding the textbook knowledge of microtubule destabilising agents and providing novel opportunities for their use in cancer therapy.
Pharmacokinetics and pharmacodynamics of PF‐05190457: The first oral ghrelin receptor inverse agonist to be profiled in healthy subjects
Authors: Denney William S. , Sonnenberg Gabriele E. , Carvajal‐Gonzalez Santos , Tuthill Theresa , Jackson V. Margaret
Published: September 2016

Aim

To evaluate safety, tolerability and pharmacokinetics of oral PF‐05190457, an oral ghrelin receptor inverse agonist, in healthy adults.

Methods

Single (SAD) and multiple ascending dose (MAD) studies were randomised, placebo‐controlled, double‐blind studies. Thirty‐five healthy men (age 38.2 ± 10.4 years; body mass index 24.8 ± 3.1 kg m–2 [mean ± standard deviation]) received ≥1 dose (2, 10, 40 [divided], 50, 100, 150, and 300 [single or divided] mg) of PF‐05190457 and/or placebo in the SAD. In the MAD study, 35 healthy men (age 39.7 ± 10.1 years; body mass index 25.9 ± 3.3 kg m–2) received ≥1 dose (2, 10, 40 and 100 mg twice daily) of PF‐05190457 and/or placebo daily for 2 weeks.

Results

PF‐05190457 absorption was rapid with a Tmax of 0.5–3 hours and a half‐life between 8.2–9.8 hours. PF‐05190457 dose‐dependently blocked ghrelin (1 pmol kg–1 min–1)‐induced growth hormone (GH) release with (mean [90% confidence interval]) 77% [63–85%] inhibition at 100 mg. PF‐05190457 (150 mg) delayed gastric emptying lag time by 30% [7–58%] and half emptying time by 20% [7–35%] with a corresponding decrease in postprandial glucose by 9 mg dL–1. The most frequent adverse event reported by 30 subjects at doses ≥50 mg was somnolence. PF‐05190457 plasma concentrations also increased heart rate up to 13.4 [4.8–58.2] beats min–1 and, similar to the effect on glucose and ghrelin‐induced GH, was lost within 2 weeks.

Conclusions

PF‐05190457 is a well‐tolerated first‐in‐class ghrelin receptor inverse agonist with acceptable pharmacokinetics for oral daily dosing. Blocking ghrelin receptors inhibits ghrelin‐induced GH, and increases heart rate, effects that underwent tachyphylaxis with chronic dosing. PF‐051940457 has the potential to treat centrally‐acting disorders such as insomnia.
CRISPR‐Cas9 technology and its application in haematological disorders
Authors: Zhang Han , McCarty Nami
Published: September 2016

The recent advent of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)‐CRISPR associated protein 9 (Cas9) system for precise genome editing has revolutionized methodologies in haematology and oncology studies. CRISPR‐Cas9 technology can be used to remove and correct genes or mutations, and to introduce site‐specific therapeutic genes in human cells. Inherited haematological disorders represent ideal targets for CRISPR‐Cas9‐mediated gene therapy. Correcting disease‐causing mutations could alleviate disease‐related symptoms in the near future. The CRISPR‐Cas9 system is also a useful tool for delineating molecular mechanisms involving haematological malignancies. Prior to the use of CRISPR‐Cas9‐mediated gene correction in humans, appropriate delivery systems with higher efficiency and specificity must be identified, and ethical guidelines for applying the technology with controllable safety must be established. Here, the latest applications of CRISPR‐Cas9 technology in haematological disorders, current challenges and future directions are reviewed and discussed.
Disclosure policy in Tullock contests with asymmetric stochastic entry
Authors: Fu Qiang , Lu Jingfeng , Zhang Jun
Published: September 2016

We examine how disclosure policy can be optimally designed to incentivize contestants when their participation is exogenously stochastic. In a generalized Tullock contest setting with two players who are asymmetric in both their values and entry probabilities, we fully characterize the necessary and sufficient conditions under which no disclosure dominates full disclosure. We find that the comparison depends solely on a balance effect exercised by entry probabilities on the expected total effort. The optimal disclosure policy must better balance the competition. These conditions continue to hold when the precisionrof Tullock contests is endogenously chosen by the designer.
The effects of wrongful discharge protection on foreign multinationals: Evidence from transaction‐level data
Authors: Kandilov Ivan T. , Senses Mine Z.
Published: September 2016

Using detailed micro‐level data from 1977 to 1994, we analyze the impact of employment protection measures adopted across US states on the number and the value of new inbound foreign direct investment (FDI) transactions completed by foreign‐owned companies. Our findings point to a robust negative association between the implementation of employment protection laws and both the extensive and the intensive margins of FDI in the US. When states adopt regulations that increase employers’ firing costs, FDI transactions by foreign multinational companies become less frequent and decrease in value, with stronger negative impacts in more labour‐intensive industries. There is also some evidence of diversion and spillover effects from the adoption of these measures by neighbouring states.
Exporters and the environment
Authors: Holladay J. Scott
Published: September 2016

This paper documents a relationship between international trade and environmental performance at the plant level. Using a panel of establishment‐level data from 1990–2006, I estimate the relationship between export orientation, import competition and pollution emissions. I find a robust relationship between international trade and pollution levels. Exporters emit 9% to 13% less after controlling for output, but there is significant heterogeneity across industries. Import competition is associated with the exit of the smallest, most pollution‐intensive plants. There is no evidence that this result is caused by polluting firms relocating to countries with low levels of environmental regulation and importing back into the US.
Consumption, housing collateral and the Canadian business cycle
Authors: Christensen Ian , Corrigan Paul , Mendicino Caterina , Nishiyama Shin‐Ichi
Published: September 2016

How important are collateral constraints for reproducing salient features of the data? To address this question, we estimate two nested versions of a New Keynesian model: one with collateralized household debt and the frictionless version of the same model. Both versions of the model are fit to Canadian data using Bayesian methods. We argue that the presence of collateral constraints improves the performance of the model in terms of overall goodness of fit. Housing collateral helps to generate a positive correlation between consumption and house prices. Moreover, housing collateral induced spillovers boosted consumption growth during the housing market boom‐bust cycles of the late 1980s and early 2000s.
Internal trade, productivity and interconnected industries: A quantitative analysis
Authors: Albrecht Lukas , Tombe Trevor
Published: September 2016

Does trade within a country affect welfare and productivity? What are the magnitude and consequences of costs to such trade? To answer these questions, we exploit unique Canadian data to measure internal trade costs in a variety of ways—they are large and vary across sectors and provinces. To quantify their consequences for welfare and productivity, we use a recent multi‐sector trade model featuring rich input–output relationships. We find interprovincial trade is an important contributor to Canada's GDP and welfare, though there are significant costs to such trade. Reducing interprovincial trade costs by 10% yields aggregate gains of 0.9%; eliminating our preferred estimates of costs, gains average between 3% and 7%—equivalent to real GDP gains between $50 billion and $130 billion. Finally, as policy reforms are often sector specific, we liberalize sectors one at a time and find gains are largest in highly interconnected industries.
Payment choice in international trade: Theory and evidence from cross‐country firm‐level data
Authors: Hoefele Andreas , Schmidt‐Eisenlohr Tim , Yu Zhihong
Published: September 2016

When trading across borders, firms choose between different payment contracts. Theoretically, this should allow firms to trade‐off differences in financing costs and enforcement across countries. This paper provides evidence for this hypothesis employing firm‐level data from a large number of developing countries. As predicted, international transactions are more likely paid after delivery when financing costs in the source country are high and when contract enforcement is low. We extend the theory and also show empirically that the more complex an industry is, the more important is contract enforcement and the less important are financing costs for the contract choice.
The impact of autism services on mothers' psychological wellbeing
Authors: Hodgetts S. , McConnell D. , Zwaigenbaum L. , Nicholas D.
Published: September 2016

Background

Families with a child diagnosed with autism spectrum disorder (ASD) often utilize a variety of professional services. The provision of these services has many potential benefits for families; however, these services also place demands on parents, particularly mothers, to access, navigate and participate. Little is known about how involvement with these services and service systems influences the psychological wellbeing of mothers of children diagnosed with ASD. We examined the relationship between professional services and psychological wellbeing for mothers of children diagnosed with ASD.

Methods

Mothers (n = 119) of children (mean child age 10.1 years; range 2–24 years) diagnosed with ASD anonymously completed a comprehensive survey. The survey included data related to maternal psychological wellbeing, professional services received and perceptions of these services, and child, mother and household characteristics.

Results

Regression analyses revealed that maternal psychological wellbeing was positively associated with the perceived continuity of services, and negatively associated with the number of professionals involved. Child and maternal age, and household income were also statistically significant predictors of maternal psychological wellbeing.

Conclusions

The study findings draw attention to the potentially negative impact of systems‐level challenges, especially fragmentation of services, on maternal psychological wellbeing, despite positive front‐line services. In particular, our data suggest that psychological wellbeing among mothers of children with ASD may vary more as a function of service system variables than practitioner‐level or child‐level variables.
Double‐barrelled wet colostomy formation after pelvic exenteration for locally advanced or recurrent rectal cancer
Authors: Bloemendaal A. L. A. , Kraus R. , Buchs N. C. , Hamdy F. C. , Hompes R. , Cogswell L. , Guy R. J.
Published: September 2016

Aim

In advanced pelvic cancer it may be necessary to perform a total pelvic exenteration. In such cases urinary tract reconstruction is usually achieved with the creation of an ileal conduit with a urinary stoma on the right side of the patient's abdomen and an end colostomy separately on the left. The potential morbidity from a second stoma may be avoided by the use of a double‐barrelled wet colostomy (DBWC), as a single stoma. Another advantage is the possibility of using a vertical rectus abdominis muscle flap for perineal reconstruction.

Method

All patients undergoing formation of a DBWC were included.

Result

A DBWC was formed in 10 patients. One patient underwent formation of a double‐barrelled wet ileostomy.

Conclusions

In this technical note we present our early experience in 11 cases and a video of DBWC formation in a male patient.
Oncological results of extended resection for locally advanced rectal cancer: the value of postirradiation MRI in predicting local recurrence
Authors: Räsänen M. , Ristimäki A. , Savolainen R. , Renkonen‐Sinisalo L. , Lepistö A.
Published: September 2016

Aim

The primary purpose of this study was to analyse the overall survival and local recurrence rate after extended resection of locally advanced rectal cancer. The second aim was to determine the ability of the response to radiological irradiation to predict R0 resection.

Method

A retrospective study was performed of 94 consecutive patients with locally advanced rectal cancer operated on at the Helsinki University Hospital, Helsinki, Finland between 2005 and 2013. Data were collected from patient records. All patients were treated with an en bloc resection. Sixty‐two patients received preoperative long‐term chemoradiotherapy.

Results

The 30‐day mortality was 3.2%. Local recurrence occurred in 10 (10.6%) patients. The cumulative 1‐, 3‐ and 5‐year overall survival to each year was 89.4%, 68.3% and 51.8%. The most important prognostic factor for both local recurrence (P = 0.006) and survival (P = 0.003) was an R0 resection. A poor or no response seen on posttreatment MRI predicted local recurrence (P = 0.045) and decreased disease‐free survival in patients treated curatively (P = 0.052). The histological tumour regression grade was not associated with local recurrence or survival.

Conclusion

Multivisceral resection offers a 5‐year survival of over 50% and local control of advanced rectal cancer in nearly 90% of carefully selected patients.
Efficacy and safety of initial combination therapy with gemigliptin and metformin compared with monotherapy with either drug in patients with type 2 diabetes: A double‐blind randomized controlled trial (INICOM study)
Authors: Lim Soo , Han Kyung Ah , Yu JaeMyung , Chamnan Parinya , Kim Eun Sook , Yoon Kun‐Ho , Kwon Sam , Moon Min Kyong , Lee Kwan Woo , Kim Dong‐Jun , Kim Mikyung , Wongtanate Manaj , Kim Eun Young , Kim Sung‐Ho , Lee Moon‐Kyu ,   INICOM Study Group
Published: September 2016

Background

Gemigliptin is a new dipeptidyl peptidase‐IV inhibitor. We investigated the efficacy and safety of initial combination therapy with gemigliptin and metformin compared with monotherapy with either drug in patients with type 2 diabetes (T2D).

Methods

A total of 433 T2D patients with a glycosylated haemoglobin (HbA1c) level of 7.5% to 11.0% and a fasting plasma glucose (FPG) concentration <270 mg/dL were randomly assigned to 3 groups: (1) gemigliptin 50 mg qd + metformin 1000 to 2000 mg qd (titrated individually), (2) gemigliptin 50 mg qd, or (3) metformin 1000 to 2000 mg qd. The primary end‐point was the change in HbA1c level after 24 weeks. Secondary end‐points were the changes in FPG, insulin, proinsulin and C‐peptide levels. The percentages of responders who achieved an HbA1c level <7% (or <6.5%) were compared between treatment groups.

Results

Baseline HbA1c levels were 8.7% in all groups. The mean changes in HbA1c level from baseline to week 24 were −2.06%, −1.24% and −1.47% in the combination, gemigliptin monotherapy and metformin monotherapy groups, respectively. The 95% confidence intervals for between‐group differences in HbA1c changes were −1.02 to −0.63 in the combination group vs the gemigliptin group and −0.82 to −0.41 vs the metformin group, which confirmed the superiority of combination therapy. A significantly higher percentage of patients in the combination therapy group reached the target HbA1c level <7% (or <6.5%) compared with the monotherapy groups. No severe side effects were observed.

Conclusions

In T2D patients, the initial combination of gemigliptin and metformin had superior efficacy without safety concerns compared with monotherapy with either drug.
Evaluation of the efficacy, safety and glycaemic effects of evolocumab (AMG 145) in hypercholesterolaemic patients stratified by glycaemic status and metabolic syndrome
Authors: Blom Dirk J. , Koren Michael J. , Roth Eli , Monsalvo Maria Laura , Djedjos C. Stephen , Nelson Patric , Elliott Mary , Wasserman Scott M. , Ballantyne Christie M. , Holman Rury R.
Published: September 2016

Aim

To examine the lipid and glycaemic effects of 52 weeks of treatment with evolocumab.

Materials and Methods

The Durable Effect of PCSK9 Antibody Compared with Placebo Study (DESCARTES) was a 52‐week placebo‐controlled trial of evolocumab that randomized 905 patients from 88 study centres in 9 countries, with 901 receiving at least one dose of study drug. For this post‐hoc analysis, DESCARTES patients were categorized by baseline glycaemic status: type 2 diabetes, impaired fasting glucose (IFG), metabolic syndrome (MetS) or none of these. Monthly subcutaneous evolocumab (420 mg) or placebo was administered. The main outcomes measured were percentage change in LDL‐cholesterol (LDL‐C) at week 52 and safety.

Results

A total of 413 patients had dysglycaemia (120, type 2 diabetes; 293, IFG), 289 had MetS (194 also had IFG) and 393 had none of these conditions. At week 52, evolocumab reduced LDL‐C by >50% in all subgroups, with favourable effects on other lipids. No significant differences in fasting plasma glucose, HbA1c, insulin, C‐peptide or HOMA indices were seen in any subgroup between evolocumab and placebo at week 52. The overall incidence of new‐onset diabetes mellitus did not differ between placebo (6.6%) and evolocumab (5.6%); in those with baseline normoglycaemia, the incidences were 1.9% and 2.7%, respectively. Incidences of AEs were similar in evolocumab‐ and placebo‐treated patients.

Conclusions

Evolocumab showed encouraging safety and efficacy at 52 weeks in patients with or without dysglycaemia or MetS. Changes in glycaemic parameters did not differ between evolocumab‐ and placebo‐treated patients within the glycaemic subgroups examined.
Preferential Liberalization, Antidumping, and Safeguards: Stumbling Block Evidence from MERCOSUR
Authors: Bown Chad P. , Tovar Patricia
Published: September 2016

There is not yet consensus in the trade agreements literature as to whether preferential liberalization leads to more or less multilateral liberalization. However, research thus far has focused mostly on tariff measures of import protection. We develop more comprehensive measures of trade policy that include the temporary trade barrier (TTB) policies of antidumping and safeguards; studies in other contexts have also shown how these policies can erode some of the trade liberalization gains that arise when examining tariffs alone. We examine the experiences of Argentina and Brazil during the formation of the MERCOSUR over 1990–2001, and we find that an exclusive focus on applied tariffs may lead to a mischaracterization of the relationship between preferential liberalization and liberalization toward non‐member countries. First, any “building block” evidence that arises by focusing on tariffs during the period in which MERCOSUR was only a free trade area can disappear once we also include changes in import protection that arise through TTBs. Furthermore, there is also evidence of a “stumbling block” effect of preferential tariff liberalization for the period in which MERCOSUR became a customs union, and this result tends to strengthen upon inclusion of TTBs. Finally, we also provide a first empirical examination of whether market power motives can help explain the patterns of changes to import protection that are observed in these settings.
Search for protective factors for psychosis – a population‐based sample with special interest in unaffected individuals with parental psychosis
Authors: Keskinen Emmi , Marttila Riikka , Koivumaa‐Honkanen Heli , Moilanen Kristiina , Keinänen‐Kiukaanniemi Sirkka , Timonen Markku , Isohanni Matti , McGrath John , Miettunen Jouko , Jääskeläinen Erika
Published: September 2016

Aim

To find factors that are associated with not having psychotic illness in a prospective general population sample, with a special interest in individuals with parental psychosis.

Methods

Data from the Northern Finland Birth Cohort 1966 (n = 10 458) and several registers were used to detect individuals with and without parental psychosis. Altogether, 594 persons had parent(s) with psychosis and 48 of them also had psychosis subsequently. Variables related to pregnancy and birth, family and childhood, health and habits in adolescence, school performance and physical activity were studied to identify determinants of unaffected status among individuals with and without parental psychosis.

Results

In the parental psychosis group, the unaffected persons had more likely a mother who was non‐depressed during pregnancy, and who worked outside the home or studied than among those who developed psychosis.

Conclusions

Protective factors for psychosis were surprisingly few in this sample. These factors were related to the mother's non‐depressed mood and the mother's work outside the home or studies. This could relate to better health and functioning of a mother. This work highlights the need for more research on protective factors for psychosis in order to identify methods for prevention of psychosis.
Brazilian guidelines on hematopoietic stem cell transplantation in acute myeloid leukemia
Authors: Silla Lucia , Dulley Frederico , Saboya Rosaura , Kerbauy Fabio , de Moraes Arantes Adriano , Pezzi Annelise , Gross Luisa Grave , Paton Eduardo , Hamerschlak Nelson
Published: September 2016

Introduction/Objectives

Acute myeloid leukemia (AML) accounts for 90% of all cases of acute leukemia in adults. In Brazil, the mortality from myeloid leukemia is 1.74/100 000 men and 1.37/100 000 women. Our aim was to review and update guidelines of the Brazilian Society of Bone Marrow Transplantation on indications of hematopoietic stem cell transplantation (HSCT) for the treatment AML.

Conclusions

(i) Allo‐HSCT is recommended for high‐risk AML (IA); (ii) allo‐HSCT is recommended for AML of intermediate risk (IA); (iii) allo‐HSCT is recommended for AML relapsed/refractory (C4); (iv) auto‐HSCT is recommended for AML after 1 consolidation (C4); (v) auto‐HSCT is recommended for AML in CR1 (higher than QT in the Brazilian experience) (C4); (vi) auto‐HSCT is accepted for AML M3 in second molecular complete remission (2B); (vii) peripheral blood instead of Bone Marrow HSC for advanced disease (2A); (viii) recommended conditioning protocols: Bu‐Cy/Bu‐Mel, Bu‐Flu, TBI‐Cy. In umbilical cord HSCT, consider ATG‐based protocols (2A); (ix) allogeneic HSCT for the treatment of AML can be used in patients between 60 and 80 yr with good performance status and the absence of significant comorbidities (C4).
Von Willebrand disease – the ‘Dos’ and ‘Don'ts’ in surgery
Authors: Miesbach Wolfgang , Berntorp Erik
Published: September 2016

Von Willebrand disease (VWD) is the most common genetic bleeding disorder. VWD is caused by a deficiency or dysfunction of von Willebrand factor (VWF), a plasma protein that mediates the initial adhesion of platelets at sites of vascular injury and binds and stabilises coagulation factor VIII (FVIII) in the blood. Prophylaxis of surgical bleeding in patients with VWD requires consideration of the individual situation, including the type of procedure and the bleeding rate, before decisions about treatment type, dose, duration and adjunctive therapy with antifibrinolytics or antithrombotic prophylaxis can be made. Although desmopressin (DDAVP)‐stimulated release of endogenous VWD is an effective treatment strategy in many patients, plasma concentrates containing VWF are the preferred option for most patients undergoing surgical procedures. Recommendations for the management of surgery in patients with VWD are summarised, including the severity of VWD and the type of the surgical procedure.
Expression of key components of the RNAi machinery are suppressed in Apis mellifera that suffer a high virus infection
Authors: De Smet Lina , Ravoet Jorgen , Wenseleers Tom , de Graaf Dirk C.
Published: September 2016

Viruses are one of the major threats for honeybees and until now more than 20 different viruses have been discovered. Viruses and their hosts are engaged in a continuous arms race in which viral defense mechanisms drive the adaptive evolution of host immune genes, which in turn results in counter‐adaptations of the viral immune antagonists. The honeybee immune responses to non‐viral pathogens have been extensively studied, but little is known about the antiviral responses. Recent evidence suggests that the main mechanism of antiviral defense in insects is the RNA interference (RNAi) pathway. Furthermore, there is evidence that some viruses suppress this RNAi pathway in order to evade antiviral immunity. In the present study, we test this hypothesis by comparing the gene expression levels of some key components of the RNAi response of honeybees that were naturally infected with at least five viruses with those who were infected with only two or three viruses using a colorimetric microarray developed in‐house, called BeeClinic, and subsequently confirmed by quantitative reverse‐transcription–polymerase chain reaction (qRT‐PCR). Our results show that key components of the RNAi pathway are indeed downregulated in highly infected bees. We were able to show that high virus loads suppress key RNAi components, which results in a counteraction of the host RNAi antiviral defense. As the RNAi is a primary defense against viruses, these findings shed new light on pathogen–host interactions and can help mitigate escalating colony losses worldwide.
Inhibitory effects of dietary soyasaponin on 2,4‐dinitrofluorobenzene‐induced contact hypersensitivity in mice
Authors: Nagano Takao , Katase Mitsuru , Tsumura Kazunobu , Saito Mineki , Matsuda Tsukasa
Published: September 2016

Soyasaponins (SSs) abundant in soybean have anti‐inflammatory activities; however, their therapeutic effects on allergic contact dermatitis (ACD) remain unknown. To assess the effects of SS‐enriched diets on ACD, we used a mouse model of contact hypersensitivity (CHS). Mice were fed low‐dose or high‐dose SS‐containing diets for 3 weeks prior to CHS induction with 2,4‐dinitrofluorobenzene (DNFB). The low‐dose SS diet attenuated DNFB‐induced ear swelling and tissue oedema, and reduced the number of infiltrating Gr‐1‐positive myeloid cells. Low‐dose, but not high‐dose, SSs decreased chemokine (C‐X‐C motif) ligand 2 (CXCL2) and triggering receptor expressed on myeloid cells (TREM)‐1 production in ear tissues, compared to a control. Taxonomic 16S rRNA analysis revealed significant alterations in faecal microbiota caused by CHS, which were reversed by low‐dose SSs. The low‐dose SS and non‐CHS groups clustered together, while the high‐dose SS group split between CHS and non‐CHS clusters. Our results demonstrated that low‐dose SSs alleviated CHS symptoms by attenuating inflammation and improving the intestinal microbiota composition, suggesting that dietary SSs may have beneficial effects on ACD.
Characterization of the early local immune response to Ixodes ricinus tick bites in human skin
Authors: Glatz Martin , Means Terry , Haas Josef , Steere Allen C. , Müllegger Robert R.
Published: September 2016

Little is known about the immunomodulation by tick saliva during a natural tick bite in human skin, the site of the tick‐host interaction. We examined the expression of chemokines, cytokines and leucocyte markers on the mRNA levels and histopathologic changes in human skin biopsies of tick bites (n=37) compared to unaffected skin (n=9). Early tick‐bite skin lesions (<24 hours of tick attachment) were characterized by a predominance of macrophages and dendritic cells, elevated mRNA levels of macrophage chemoattractants (CCL2, CCL3, CCL4) and neutrophil chemoattractants (CXCL1, CXCL8), of the pro‐inflammatory cytokine, IL‐1β, and the anti‐inflammatory cytokine, IL‐5. In contrast, the numbers of lymphocytes and mRNA levels of lymphocyte cell markers (CD4, CD8, CD19), lymphocyte chemoattractants (CXCL9, CXCL10, CXCL11, CXCL13, CCL1, CCL22), dendritic cell chemoattractants (CCL20), and other pro‐ (IL‐6, IL‐12p40, IFN‐γ, TNF‐α) and anti‐inflammatory cytokines (IL‐4, IL‐10, TGF‐β) did not differ from normal skin. With longer tick attachment (>24 hours), the numbers of innate immune cells and mediators (not significantly) declined, whereas the numbers of lymphocytes (not significantly) increased. Natural tick bites by Ixodes ricinus ticks initially elicit a strong local innate immune response in human skin. Beyond 24 hours of tick attachment, this response usually becomes less, perhaps because of immunomodulation by tick saliva.
Should hidradenitis suppurativa/acne inversa best be renamed as “dissecting terminal hair folliculitis”?
Authors: Chen WenChieh , Plewig Gerd
Published: September 2016

Hidradenitis suppurativa/acne inversa is a diverse, enigmatic and distressful disease that has aroused growing interest in specialists from different disciplines. Both names describe its classical manifestations in the intertriginous regions and reflect the historical view of the disease definition, but cause confusions in the understanding of its pathogenesis and classification. In the light of the advance in clinical, histopathological and pathophysiological findings, we propose the term “dissecting terminal hair folliculitis” (DTHF) to characterize its disease nature as folliculitis instead of acneiform disease or apocrine gland disorder. DTHF attacks exclusively the terminal hair follicles in an overwhelming majority of adults, initiating from the fragile acroinfundibulum leading to a non‐infectious overreaction of innate immunity system with inflammation that may fiercely dissect and engulf all the surrounding tissues accompanied by secondary bacterial infections. Evidence indicates that perifolliculitis capitis abscedens et suffodiens and pilonidal disease are very likely regional variants of DTHF with the same pathogenesis. Treatment of DTHF remains frustrating. The benefit of biologics in targeting inflammation is so far non‐specific, palliative and inconsistent. Hair epilation and photodynamic therapy in treatment of the disease is questionable in consideration of the pathogenesis. Genetic and translational research, especially on the Notch signalling pathways, will yield breakthrough in the development of novel treatment modalities.
How to Attract an Audience at a Conference: Paper, Person or Place?
Authors: Günther Isabel , Grosse Melanie , Klasen Stephan
Published: September 2016

We analyze the drivers of audience size and the number of questions asked in parallel sessions at the annual conference of the German Economics Association. We find that the location of the presentation is at least as important for the number of academics attending a talk as the combined effect of the person presenting and the paper presented. Being a presenter in a late morning session on the second day of a conference, close to the place where coffee is served, significantly increases the size of the audience. When it comes to asking questions, location becomes less important, but smaller rooms lead to more questions being asked. Younger researchers and very senior researchers attract more questions and comments. There are also interesting gender effects. Women attend research sessions more diligently than men, but seem to ask fewer questions than men. Men are less likely to attend presentations on health, education, welfare and development economics than women. Our findings suggest that strategic scheduling of sessions could ensure better participation at conferences. Moreover, different behaviors of men and women at conferences might also contribute to the lack of women in senior scientist positions.
Evaluative Practices in Qualitative Management Research: A Critical Review
Authors: Symon Gillian , Cassell Catherine , Johnson Phil
Published: September 2016

This paper critically reviews commentaries on the evaluation and promotion of qualitative management research. The review identifies two disjunctures: between methodological prescriptions for epistemologically diverse criteria and management journal prescriptions for standardized criteria; and between the culturally dependent production of criteria and their positioning in editorials and commentaries as normative and objective. The authors’ critical social constructionist analysis surfaces underlying positivist assumptions and institutional processes in these commentaries, which they argue are producing (inappropriate) homogeneous evaluation criteria for qualitative research, marginalizing alternative perspectives, and disciplining individual qualitative researchers into particular normative practices. The authors argue that interventions to encourage more qualitative research need to focus as much on editorial, disciplinary and institutional practices as the practices of individual researchers, and they make recommendations for changes that may allow qualitative management research to develop in a more supportive context by recognizing philosophical diversity as legitimate.
Predicting survival in node‐positive prostate cancer after open, laparoscopic or robotic radical prostatectomy: A competing risk analysis of a multi‐institutional database
Authors: Schiavina Riccardo , Bianchi Lorenzo , Borghesi Marco , Briganti Alberto , Brunocilla Eugenio , Carini Marco , Terrone Carlo , Mottrie Alex , Dente Donato , Gacci Mauro , Gontero Paolo , Gurioli Alberto , Imbimbo Ciro , La Manna Gaetano , Marchioro Giansilvio , Milanese Giulio , Mirone Vincenzo , Montorsi Francesco , Morgia Giuseppe , Munegato Stefania , Novara Giacomo , Panarello Daniele , Porreca Angelo , Russo Giorgio I , Serni Sergio , Simonato Alchide , Urzì Daniele , Verze Paolo , Volpe Alessandro , Martorana Giuseppe
Published: September 2016

Objectives

To investigate cancer‐specific mortality and other‐cause mortality in prostate cancer patients with nodal metastases.

Methods

The study included 411 patients treated with radical prostatectomy and pelvic lymph node dissection for prostate cancer with lymph node metastases at 10 tertiary care centers between 1995 and 2014. Kaplan–Meier analyses were used to assess cancer‐specific mortality‐free survival rates at 8 years' follow up in the overall population, and after stratifying patients according to clinical and pathological parameters. Uni‐ and multivariable competing risk Cox regression analyses were used to assess cancer‐specific mortality and other‐cause mortality. Finally, cumulative‐incidence plots were generated for cancer‐specific mortality and other‐cause mortality after stratifying patients according to the number of positive lymph nodes and the median age at surgery, according to the competing risks method.

Results

Men with prostate‐specific antigen ≤40 ng/mL and those with one to three positive lymph nodes showed higher cancer‐specific mortality‐free survival estimates as compared with their counterparts with prostate‐specific antigen >40 ng/mL and >3 metastatic lymph nodes, respectively (all P < 0.001). At multivariable Cox regression analyses, preoperative prostate‐specific antigen >40 ng/mL, >3 lymph node metastases and pathological Gleason score 8–10 were all independent predictors of cancer‐specific mortality (all P‐values ≤0.001). On competing risk analysis, when patients were stratified according to the number of positive lymph nodes (namely, ≤3 vs >3), the 8‐year cancer‐specific mortality rates were 27.4% versus 44.8% for patients aged <65 years, and 15.2% versus 52.6% for patients aged ≥65 years, respectively.

Conclusions

Three positive lymph nodes represent the best prognostic cut‐off in node‐positive prostate cancer patients. In those individuals with >3 positive lymph nodes, the overall mortality rate is completely related to prostate cancer in young patients.
Retrospective observational analysis of the use of an architecturally unique dermal regeneration template (Derma Pure®) for the treatment of hard‐to‐heal wounds
Authors: Kimmel Howard , Gittleman Haley
Published: September 2016

The purpose of this analysis was to evaluate the use of DermaPure, a decellularised human skin allograft, in the treatment of a variety of challenging wounds. This retrospective observational analysis reviewed a total of 37 patients from 29 different wound clinics across the USA. Each patient received one application of DermaPure which was followed until complete closure. A statistical analysis was performed with the end point being complete healing. All wounds on average, had a duration of 56 weeks and healed in an average time of 10·58 weeks. Individual wound categories included diabetic foot ulcers, which healed in 8·21 weeks; venous leg ulcers, which healed in 11·29 weeks; and surgical/traumatic wounds, which healed in 11·8 weeks.
Biogeographical homogeneity of Caribbean coral reef benthos
Authors: Pawlik Joseph R. , Loh Tse‐Lynn
Published: September 2016

Caribbean reef benthic assemblages have been considered biogeographically homogeneous at regional scales, but this concept was recently challenged by Williams et al. (2015, Journal of Biogeography, 42, 1327–1335). These authors concluded that benthic assemblages exhibit considerable biogeographical variability at regional and smaller scales, that rugosity and wave exposure play key roles in structuring assemblages, and that homogenization has yet to occur at a regional scale. We reassess their conclusions using recently published benthic and fish surveys that targeted sites either protected from fishing or intensively overfished. For sponges, regional variation in assemblages is mostly attributable to the removal of chemically undefended species by sponge‐eating fishes at sites protected from overfishing. We maintain that Caribbean benthic assemblages are remarkably homogeneous when compared to reefs in other tropical regions, and were likely more homogeneous before the localized effects of intensive fishing resulted in top‐down ecosystem alterations in benthic assemblages.
The prevalence of anxiety in patients with psoriasis: a systematic review of observational studies and clinical trials
Authors: Fleming P. , Bai J.W. , Pratt M. , Sibbald C. , Lynde C. , Gulliver W.P.
Published: September 2016

Psoriasis and anxiety are chronic conditions with significant morbidity and there is evidence that they may exacerbate one another. There is little data on the prevalence of anxiety in psoriasis and the effect of psoriasis treatment on comorbid anxiety. The objective of this study was to perform a systematic review of the literature to describe the prevalence and severity of clinical anxiety disorders or anxiety symptoms among adult patients with psoriasis and characterize the effect of anti‐psoriatic interventions on clinical anxiety disorders or anxiety symptoms. We searched PubMed, EMBASE, and the Cochrane Database using search terms ‘psoriasis’ and ‘anxiety’. Results were tabulated and verified by two independent reviewers. Meta‐analyses were not performed due to heterogeneity of data. Of 213 publications identified, 938 194 patients from 15 papers were included. The mean age ranged from 31.9–59.4 years old, with a mean PASI score of 7.65–22.8 (reported by nine studies) and a body surface area involvement of 25.9–39.8% (reported by two studies). The prevalence of anxiety in patients with psoriasis was 7–48%, which was significantly higher than healthy controls in two of three studies (HR 1.29–1.31, P = 0.001 and OR 2.91 [95% CI, 2.01–4.21], P < 0.001). Four of five studies (n = 2029) demonstrated an improvement in anxiety symptoms with psoriasis treatment. This review demonstrates a high prevalence of anxiety of adult patients with psoriasis suggesting that patients would benefit from systematic screening. Although the data suggest that anxiety may be improved through various psoriasis treatments, larger prospective randomized trials are needed to confirm this effect.