bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of strategic tillage on short-term erosion, nutrient loss in runoff and greenhouse gas emissions
Authors: Melland A. R. , Antille D. L. , Dang Y. P.
Published: October 2016

Occasional strategic tillage (ST) of long-term no-tillage (NT) soil to help control weeds may increase the risk of water, erosion and nutrient losses in runoff and of greenhouse gas (GHG) emissions compared with NT soil. The present study examined the short-term effect of ST on runoff and GHG emissions in NT soils under controlled-traffic farming regimes. A rainfall simulator was used to generate runoff from heavy rainfall (70mmh–1) on small plots of NT and ST on a Vertosol, Dermosol and Sodosol. Nitrous oxide (N2O), carbon dioxide (CO2) and methane (CH4) fluxes from the Vertosol and Sodosol were measured before and after the rain using passive chambers. On the Sodosol and Dermosol there was 30% and 70% more runoff, respectively, from ST plots than from NT plots, however, volumes were similar between tillage treatments on the Vertosol. Erosion was highest after ST on the Sodosol (8.3tha–1 suspended sediment) and there were no treatment differences on the other soils. Total nitrogen (N) loads in runoff followed a similar pattern, with 10.2kgha–1 in runoff from the ST treatment on the Sodosol. Total phosphorus loads were higher after ST than NT on both the Sodosol (3.1 and 0.9kgha–1, respectively) and the Dermosol (1.0 and 0.3kgha–1, respectively). Dissolved nutrient forms comprised less than 13% of total losses. Nitrous oxide emissions were low from both NT and ST in these low-input systems. However, ST decreased CH4 absorption from both soils and almost doubled CO2 emissions from the Sodosol. Strategic tillage may increase the susceptibility of Sodosols and Dermosols to water, sediment and nutrient losses in runoff after heavy rainfall. The trade-offs between weed control, erosion and GHG emissions should be considered as part of any tillage strategy.
Averting Behaviors of Very Small Radiation Exposure via Food Consumption after the Fukushima Nuclear Power Station Accident
Authors: Ito Nobuyuki , Kuriyama Koichi
Published: October 2016

This article considers changes in the perception and avoidance behavior of food risks over time. In Japan, consumers’ concerns about the risks of radiation exposure via food consumption rose rapidly after the accident at the Fukushima Daiichi Nuclear Power Station in 2011. We conducted choice experiment surveys three months, seven months, and eleven months after the Fukushima accident and simulated the conditional means of willingness to pay (WTP) for avoiding radiation exposure via food consumption in each survey period. The results show that although the characteristics of changes in averting behaviors vary depending on the type of food, the heterogeneity in WTP values for avoiding food risk tends to reduce (broaden) when their magnitude decreases (increases).
Using Pneumococcal Carriage Data to Monitor Postvaccination Changes in the Incidence of Pneumococcal Otitis Media
Authors: Flasche Stefan , Givon-Lavi Noga , Dagan Ron
Published: October 2016

Pneumococcal conjugate vaccines (PCVs) have substantially reduced the burden of pneumococcal disease, including the incidence of otitis media (OM). However, in most countries, no surveillance exists to monitor the change in pneumococcal OM incidence after the introduction of PCVs. We explored whether measuring pneumococcal carriage was a useful surrogate for monitoring postvaccination changes in the incidence of pneumococcal OM. The 7-valent PCV was introduced to Israel's national immunization program in July 2009 and gradually replaced by the 13-valent PCV starting in November 2010. Each day since 2009, nasopharyngeal swabs have been obtained from the first 4 Bedouin children and the first 4 Jewish children who were younger than 5 years old and attended a pediatric emergency room in southern Israel. During the same time, OM surveillance in southern Israel included all children younger than 2 years of age who were diagnosed with OM and had undergone a middle-ear fluid culture. The relative change in the prevalence of vaccine-serotype (VT) pneumococcal carriage was predictive of the relative change in incidence of OM due to VT pneumococcus. However, the serotype replacement observed in non-VT carriage is not paralleled in the incidence of OM due to non-VT pneumococcus. This could indicate that there are more complex mechanisms of the immune response involved in preventing initial and consecutive episodes of OM, which has been changed through declining prevalence of the most virulent serotypes as a result of vaccination.
Comparison of Dietary Intakes Between a Large Online Cohort Study (Etude NutriNet-Santé) and a Nationally Representative Cross-Sectional Study (Etude Nationale Nutrition Santé) in France: Addressing the Issue of Generalizability in E-Epidemiology
Authors: Andreeva Valentina A. , Deschamps Valérie , Salanave Benoît , Castetbon Katia , Verdot Charlotte , Kesse-Guyot Emmanuelle , Hercberg Serge
Published: October 2016

Despite some advantages over traditional methods, Web-based studies elicit concerns about generalizability. To address this issue, we compared dietary intakes between an electronic (e-) cohort study and a nationally representative survey. We studied 49,443 French volunteers aged 18–74 years recruited during 2009–2010 in the NutriNet-Santé Study, a general population-based e-cohort study. The Etude Nationale Nutrition Santé (ENNS; 2006–2007), a cross-sectional study with a nationally representative sample of 2,754 French adults aged 18–74 years, served as the reference data set. Reported dietary intakes from three 24-hour dietary records were weighted and compared between the two studies via Student t tests for mean location, using a >5% cutoff for establishing practically meaningful differences. We observed similar intakes as regards carbohydrates, total lipids, protein, and total energy. However, intakes of fruit and vegetables, fiber, vitamins B6, B9, C, D, and E, iron, and magnesium were higher in the e-cohort than in the ENNS, while intakes of alcohol and nonalcoholic beverages were lower in the e-cohort. Significant sex-specific differences were observed regarding vitamins A and B12, zinc, and potassium. True intake differences, mode effects, and volunteer bias might each contribute to explaining the findings. In the future, repeated use of the same tool in large e-cohorts with heterogeneous dietary exposures could serve research purposes and supplement group-level monitoring of dietary trends.
Invited Commentary: Hypertension During Pregnancy and Offspring Microvascular Structure—Insights From the Retinal Microcirculation
Authors: Huckstep Odaro , Lewandowski Adam J. , Leeson Paul
Published: October 2016

Human clinical studies as well as laboratory animal studies demonstrate that offspring of pregnancies affected by common complications, such as preeclampsia and preterm birth, display developmental phenotypes that relate distinctly to the pregnancy disorder. Several studies have now found microvascular differences in offspring of hypertensive pregnancies, and there is interest in whether these may underlie epidemiologic associations between gestational hypertension and a higher risk of hypertension and stroke in the offspring. The retinal circulation provides a unique window into microvascular structure, of likely relevance to both the cerebrovasculature and broader cardiovascular risk. Yesil et al. (Am J Epidemiol. 2016;184(9):605–615) report in this issue of the Journal that maternal gestational blood pressure elevation is associated with reduced retinal vascular caliber in offspring at 6 years of age, providing a link between variation in pregnancy characteristics and childhood vascular development. Further work to understand the longitudinal association between pregnancy, emergence of microvascular changes, and cardiovascular risk may identify opportunities for future preventive interventions.
The Relationship Between School Holidays and Transmission of Influenza in England and Wales
Authors: Jackson Charlotte , Vynnycky Emilia , Mangtani Punam
Published: October 2016

School closure is often considered as an influenza control measure, but its effects on transmission are poorly understood. We used 2 approaches to estimate how school holidays affect the contact parameter (the per capita rate of contact sufficient for infection transmission) for influenza using primary care data from England and Wales (1967–2000). Firstly, we fitted an age-structured susceptible-infectious-recovered model to each year's data to estimate the proportional change in the contact parameter during school holidays as compared with termtime. Secondly, we calculated the percentage difference in the contact parameter between holidays and termtime from weekly values of the contact parameter, estimated directly from simple mass-action models. Estimates were combined using random-effects meta-analysis, where appropriate. From fitting to the data, the difference in the contact parameter among children aged 5–14 years during holidays as compared with termtime ranged from a 36% reduction to a 17% increase; estimates were too heterogeneous for meta-analysis. Based on the simple mass-action model, the contact parameter was 17% (95% confidence interval: 10, 25) lower during holidays than during termtime. Results were robust to the assumed proportions of infections that were reported and individuals who were susceptible when the influenza season started. We conclude that school closure may reduce transmission during influenza outbreaks.
Comparative analysis of recurrent events after presentation with an index myocardial infarction or ischaemic stroke
Authors: Yeo Khung Keong , Zheng Huili , Chow Khuan Yew , Ahmad Aftab , Chan Bernard P.L. , Chang Hui Meng , Chong Eric , Chua Terrance Siang Jin , Foo David Chee Guan , Low Lip Ping , Ong Marcus Eng Hock , Ong Hean Yee , Koh Tian Hai , Tan Huay Cheem , Tang Kok Foo , Venketasubramanian Narayanaswamy
Published: October 2016

Aims

Acute myocardial infarction (AMI) and stroke are important causes of mortality and morbidity. Our aims are to determine the comparative epidemiology of AMI and ischaemic stroke; and examine the differences in cardiovascular outcomes or mortality occurring after an AMI or stroke.

Methods and results

The Singapore National Registry of Diseases Office collects countrywide data on AMI, stroke, and mortality. Index events of AMI and ischaemic stroke between 2007 and 2012 were identified. Patients were then matched for occurrences of subsequent AMI, stroke, or death within 1-year of the index event. There were 33 222 patients with first-ever AMI and 20 982 with first-ever stroke. AMI patients were significantly more likely to be men (66.3% vs. 56.9%), non-Chinese (32.1% vs. 24.1%), and smokers (43.1% vs. 38.6%), but less likely to have hypertension (65.6% vs. 79%) and hyperlipidaemia (61.1% vs. 65.5%), compared with stroke patients. In total 6.8% of the AMI patients had recurrent AMI, whereas 4.8% of the stroke patients had recurrent stroke within 1 year; 31.7% of the AMI patients died, whereas 17.1% of the ischaemic stroke patients died within 1 year. Older age, Malay ethnicity, and diabetes mellitus were statistically significant risk factors for all-cause mortality and for the composite endpoint of AMI, stroke, and all-cause mortality, at 1 year.

Conclusions

Risk profiles of patients with AMI and stroke are significantly different. Patients suffer recurrent events in vascular territories similar to the index event. Age and diabetes mellitus are significant predictors of recurrent vascular events and mortality.
How to Pitch an Antibiotic Stewardship Program to the Hospital C-Suite
Authors: Spellberg Brad , Bartlett John G. , Gilbert David N.
Published: October 2016

Hospitals will soon require antibiotic stewardship programs. Infectious diseases specialists must craft business plans to engage hospital leadership to fund such programs. In this article, we review key cost and revenue elements that should be covered in such plans.

Society is placing increasing emphasis on the importance of antimicrobial stewardship programs (ASPs). New regulatory standards require hospitals to implement ASPs. Infectious Diseases (ID) specialists will need to help design and implement such programs at hospitals. A critical component of establishing such programs is submitting a business plan to hospital leadership justifying the cost and structure of the ASP and explaining what benefits the hospital will gain in return. In this article, we explore typical elements of such business plans and describe how hospital leadership may evaluate and determine the value of such plans. Understanding hospital costs and revenue models is critical to creating a viable and realistic business plan to support ASPs.
Parasite Clearance and Artemether Pharmacokinetics Parameters Over the Course of Artemether-Lumefantrine Treatment for Malaria in Human Immunodeficiency Virus (HIV)-Infected and HIV-Uninfected Ugandan Children
Authors: Kajubi Richard , Huang Liusheng , Were Moses , Kiconco Sylvia , Li Fangyong , Marzan Florence , Gingrich David , Nyunt Myaing M. , Ssebuliba Joshua , Mwebaza Norah , Aweeka Francesca T. , Parikh Sunil
Published: October 2016

Background

Artemisinins are primarily responsible for initial parasite clearance. Antimalarial pharmacokinetics (PK), human immunodeficiency virus (HIV) infection, and antiretroviral therapy have been shown to impact treatment outcomes, although their impact on early parasite clearance in children has not been well characterized.

Methods

Parasite clearance parameters were generated from twice-daily blood smears in HIV-infected and HIV-uninfected Ugandan children treated with artemether-lumefantrine (AL). Artemether and dihydroartemisinin (DHA) area-under-the-curve from 0–8 hours (AUC0-8hr) after the 1st AL dose was compared with AUC0-8hr after the last (6th) dose in a concurrently enrolled cohort. The association between post-1st dose artemisinin AUC0-8hr and parasite clearance was assessed.

Results

Parasite clearance was longer in HIV-infected versus HIV-uninfected children (median, 3.5 vs 2.8 hours; P = .003). Artemether AUC0-8hr was 3- to 4-fold lower after the 6th dose versus the 1st dose of AL in HIV-infected children on nevirapine- or lopinavir/ritionavir-based regimens and in HIV-uninfected children (P ≤ .002, 1st vs 6th-dose comparisons). Children on efavirenz exhibited combined post-1st dose artemether/DHA exposure that was significantly lower than those on lopinavir/ritonavir and HIV-uninfected children. Multiple regression analysis supported that the effect of artemether/DHA exposure on parasite clearance was significantly moderated by HIV status.

Conclusions

Parasite clearance rates remain rapid in Uganda and were not found to associate with PK exposure. However, significant decreases in artemisinin PK with repeated dosing in nearly all children, coupled with small, but significant increase in parasite clearance half-life in those with HIV, may have important implications for AL efficacy, particularly because reports of artemisinin resistance are increasing.
Increased Age-Dependent Risk of Death Associated With lukF-PV-Positive Staphylococcus aureus Bacteremia
Authors: Knudsen Trine A. , Skov Robert , Petersen Andreas , Larsen Anders R. , Benfield Thomas ,   for the Danish Staphylococcal Bacteremia Study Group
Published: October 2016

Background

Panton-Valentine leucocidin is a Staphylococcus aureus virulence factor encoded by lukF-PV and lukS-PV that is infrequent in S aureus bacteremia (SAB), and, therefore, little is known about risk factors and outcome of lukF-PV/lukS-PV-positive SAB.

Methods

This report is a register-based nationwide observational cohort study. lukF-PV was detected by polymerase chain reaction. Factors associated with the presence of lukF-PV were assessed by logistic regression analysis. Adjusted 30-day hazard ratios of mortality associated with lukF-PV status were computed by Cox proportional hazards regression analysis.

Results

Of 9490 SAB cases, 129 were lukF-PV-positive (1.4%), representing 14 different clonal complexes. lukF-PV was associated with younger age, absence of comorbidity, and methicillin-resistant S aureus. In unadjusted analysis, mortality associated with lukF-PV-positive SAB was comparable to SAB. However, lukF-PV-positive SAB nonsurvivors were significantly older and had more comorbidity. Consequently, by adjusted analysis, the risk of 30-day mortality was increased by 70% for lukF-PV-positive SAB compared with SAB (hazard ratio, 1.70; 95% confidence interval, 1.20–2.42; P = .003).

Conclusions

lukF-PV-positive SAB is rare in Denmark but associated with a significantly increased risk of mortality. Although the risk of lukF-PV-positive SAB was highest in the younger age groups, >80% of deaths associated with lukF-PV-positive SAB occurred in individuals older than 55 years.
Bacterial Colonization and Antibiotic Resistance in a Prospective Cohort of Newborn Infants During the First Year of Life
Authors: Meropol Sharon B. , Stange Kurt C. , Jacobs Michael R. , Weiss Judith K. , Bajaksouzian Saralee , Bonomo Robert A.
Published: October 2016

Background

Infants are virtually sterile at birth and frequently use antibiotics; our objective was to (1) characterize the longitudinal colonization with bacterial pathogens and associated antibiotic resistance in a cohort of community-dwelling infants in Northeast Ohio and (2) describe longitudinal concurrent antibiotic and daycare exposures.

Methods

For 35 newborns, nasopharyngeal swabs were cultured for Streptococcus pneumoniae, anterior nasal for Staphylococcus aureus, and perirectal for extended-spectrum beta-lactamase (ESBL)-producing Gram-negative enteric bacteria, at 3-month intervals for 12 months. Infant and household antibiotics and daycare exposure were assessed longitudinally.

Results

Thirteen infants received perinatal or nursery antibiotics. By 3 months, at least 22 were colonized with Gram-negative bacteria; 2 with S pneumoniae (type 19A, resistant; 15C, susceptible), 5 with methicillin-susceptible S aureus. By 12 months, at least 22 of 35 infants received antibiotics, 20 had household members with antibiotics, and 12 attended daycare; 7 more had household members with daycare exposure. The ESBL-producing organisms were not identified. At least 10 infants were colonized at some time with an antibiotic-resistant organism, 3 more with pathogens displaying intermediate resistance. Pathogen colonization and resistance were intermittent and inconsistent.

Conclusions

In a community-based cohort followed from birth, early antibiotic and daycare exposures are common, especially considering perinatal maternal exposures. Colonization patterns of Gram-negative bacteria, S pneumoniae, S aureus, and resistant pneumococci are strikingly dynamic. Further research can identify key areas for potential interventions to maximize clinical antibiotic outcomes while minimizing future resistance.
Carbapenem-Resistant Klebsiella pneumoniae Infection in Three New York City Hospitals Trended Downwards From 2006 to 2014
Authors: Park Sun O. , Liu Jianfang , Furuya E. Yoko , Larson Elaine L.
Published: October 2016

Background

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection is a rising public health threat since its first outbreaks in New York City (NYC) in the early 2000s. We investigated annual trends of CRKP infection in hospital-acquired infections (HAIs) and community-onset infections (COIs) treated in 3 NYC hospitals from 2006 to 2014.

Methods

We extracted K pneumoniae infection data including carbapenem susceptibility and anatomical sites, compared clinical characteristics between CRKP and carbapenem-susceptible K pneumoniae infections, and determined CRKP infection proportions in total K pneumoniae infections in HAI and COI to identify statistically significant trends from 2006 to 2014 using the Cochran-Armitage trend test.

Results

Carbapenem-resistant K pneumoniae contributed 17.3% (601 of 3477) of hospital-acquired K pneumoniae infection compared with 7.7% (149 of 1926) in COI from 2006 to 2014. Carbapenem-resistant K pneumoniae proportions in HAI and COI were positively correlated over time (r = 0.83, P < .01), and there were downward annual trends of CRKP proportions from 2006 to 2014 in both HAI and COI (25.8% to 10.5% in HAI, P < .001; 13.6% to 3.1% in COI, P < .001). By anatomical site, significant downward annual trends were present only in urinary tract infection (P < .001 for both HAI and COI) from 2006 to 2014.

Conclusions

Annual trends of CRKP proportions from 2006 to 2014 were downward in both HAI and COI, and HAI and COI were positively correlated. Efforts to reduce and prevent CRKP infections in both hospital and community settings were successful and warrant continuation.
Altered Monocyte and Endothelial Cell Adhesion Molecule Expression Is Linked to Vascular Inflammation in Human Immunodeficiency Virus Infection
Authors: Kulkarni Manjusha , Bowman Emily , Gabriel Janelle , Amburgy Taylor , Mayne Elizabeth , Zidar David A. , Maierhofer Courtney , Turner Abigail Norris , Bazan Jose A. , Koletar Susan L. , Lederman Michael M. , Sieg Scott F. , Funderburg Nicholas T.
Published: October 2016

Background

Human immunodeficiency virus (HIV)-infected individuals have increased risk for vascular thrombosis, potentially driven by interactions between activated leukocytes and the endothelium.

Methods

Monocyte subsets (CD14+CD16−, CD14+CD16+, CD14DimCD16+) from HIV negative (HIV−) and antiretroviral therapy-treated HIV positive (HIV+) participants (N = 19 and 49) were analyzed by flow cytometry for adhesion molecule expression (lymphocyte function-associated antigen 1 [LFA-1], macrophage-1 antigen [Mac-1], CD11c/CD18, very late antigen [VLA]-4) and the fractalkine receptor (CX3CR1); these receptors recognize ligands (intercellular adhesion molecules [ICAMs], vascular cell adhesion molecule [VCAM]-1, fractalkine) on activated endothelial cells (ECs) and promote vascular migration. Plasma markers of monocyte (soluble [s]CD14, sCD163) and EC (VCAM-1, ICAM-1,2, fractalkine) activation and systemic (tumor necrosis factor receptor [TNFR-I], TNFR-II) and vascular (lipoprotein-associated phospholipase A2 [Lp-PLA2]) inflammation were measured by enzyme-linked immunosorbent assay.

Results

Proportions of CD16+ monocyte subsets were increased in HIV+ participants. Among all monocyte subsets, levels of LFA-1 were increased and CX3CR1 levels were decreased in HIV+ participants (P < .01). Levels of sCD163, sCD14, fractalkine, ICAM-1, VCAM-1, TNFR-II, and Lp-PLA2 were also increased in HIV+ participants (P < .05), and levels of sCD14, TNFR-I, and TNFR-II were directly related to ICAM-1 and VCAM-1 levels in HIV+ participants. Expression of CX3CR1 on monocyte subsets was inversely related to plasma Lp-PLA2 (P < .05 for all).

Conclusions

Increased proportions of CD16+ monocytes, cells with altered adhesion molecule expression, combined with elevated levels of their ligands, may promote vascular inflammation in HIV infection.
Particle physics as a way to bring different cultures to work together in science
Authors: Mikenberg G.
Published: October 2016

Science has traditionally played an important role in sharing knowledge among people. Particle physics, with its large experiments, has shown that one can not only share the knowledge among different cultures, but that one can also work together to achieve this knowledge. The present article gives a few examples where this has been possible among people that are sometimes in conflict situations.
Giant Basal Cell Carcinomas Express Neuroactive Mediators and Show a High Growth Rate: A Case–Control Study and Meta-Analysis of Etiopathogenic and Prognostic Factors
Authors: Yazdani Abyaneh Mohammad-Ali , Engel Peter , Slominski Andrzej , Ragsdale Bruce , Agag Richard , Cramer Daniel , Carlson J. Andrew
Published: October 2016

Background:

Giant basal cell carcinomas (GBCCs), (BCC ≥ 5 cm), are often painless, destructive tumors resulting from poorly understood patient neglect.

Objectives:

To elucidate etiopathogenic factors distinguishing GBCC from basal cell carcinoma (BCC) and identify predictors for disease-specific death (DSD).

Methods:

Case–control study examining clinicopathologic and neuroactive factors (β-endorphin, met-enkephalin, serotonin, adrenocorticotropic hormone, and neurofilament expression) in GBCC and BCC. Systematic literature review to determine DSD predictors.

Results:

Thirteen GBCCs (11 patients) were compared with 26 BCCs (25 patients). GBCC significantly differed in size, disease duration, and outcomes; patients were significantly more likely to live alone, lack concern, and have alcoholism. GBCC significantly exhibited infiltrative/morpheic phenotypes, perineural invasion, ulceration, and faster growth. All neuromediators were similarly expressed. Adenoid phenotype was significantly more common in GBCC. Adenoid tumors expressed significantly more β-endorphin (60% vs. 18%, P = 0.01) and serotonin (30% vs. 4%, P = 0.02). In meta-analysis (n ≤ 311: median age 68 years, disease duration 90 months, tumor diameter 8 cm, 18.4% disease-specific mortality), independent DSD predictors included tumor diameter (cm) (hazard ratio (HR): 1.12, P = 0.003), bone invasion (HR: 4.19, P = 0.015), brain invasion (HR: 8.23, P = 0.001), and distant metastases (HR: 14.48, P = 0.000).

Conclusions:

GBCC etiopathogenesis is multifactorial (ie, tumor biology, psychosocial factors). BCC production of paracrine neuromediators deserves further study.
Use of dietary assessment tools in randomized trials evaluating diet-based interventions in pregnancy: a systematic review of literature
Authors: Al Wattar Bassel H. , Mylrea-Lowndes Bronacha , Morgan Catrin , Moore Amanda P. , Thangaratinam Shakila
Published: October 2016

Purpose of review

Accurate assessment of dietary intake in interventional trials is the key to evaluate changes in dietary behaviour and compliance. We evaluated the use of dietary assessment tools in randomized trials on diet-based interventions in pregnancy by a systematic review.

Recent findings

We updated our previous search (until January 2012) on trials of diet and lifestyle interventions in pregnancy using Medline and EMBASE up to December 2015. Two independent reviewers undertook study selection and data extraction. We assessed the characteristics of dietary assessment tools, the timing and frequency of use and any validation undertaken.

Two-thirds (39/58, 67%) of the included studies used some form of tools to assess dietary intake. Multiple days’ food diaries were the most commonly used (23/39, 59%). Three studies (3/39, 8%) validated the used tools in a pregnant population. Three studies (3/39, 8%) prespecified the criteria for adherence to the intervention. The use of dietary assessment tools was not associated with study quality, year of publication, journal impact factor, type of journal and the study sample size.

Although self-reporting dietary assessment tools are widely used in interventional dietary trials in pregnancy, the quality and applicability of existing tools are low.
Twin pregnancy complicated by selective growth restriction
Authors: Townsend Rosemary , Khalil Asma
Published: October 2016

Purpose of review

Selective intrauterine growth restriction (sIUGR) in twin pregnancies presents a complex management problem for the fetal medicine specialist. This review summarizes what is currently known about sIUGR pathophysiology, particularly in monochorionic pregnancies and looks at the results of early trials of fetal intervention in high-risk sIUGR pregnancies.

Recent findings

sIUGR in monochorionic pregnancies is due to unequal placental sharing, but the clinical outcome is determined by the characteristics of the placental vascular anastomoses. Classification of monochorionic sIUGR by umbilical artery Doppler allows interventions to be targeted at high-risk subgroups. The overall survival after diagnosis of early-onset Type II/III sIUGR is similar after the management with cord occlusion and selective laser photocoagulation of connecting vessels.

Fetal interventions have been shown to be feasible and of potential benefit in early-onset sIUGR in a monochorionic twin pregnancy. Cord occlusion or selective laser photocoagulation of connecting vessels may be offered as an alternative to expectant management or preterm delivery in early-onset severe cases after careful discussion with the parents. Randomized controlled trial evidence is required to make a definitive judgment and to determine the impact of fetal intervention on the neurological outcomes.
Blood products and procoagulants in traumatic bleeding: use and evidence
Authors: Wong Henna , Curry Nicola , Stanworth Simon J.
Published: October 2016

Purpose of review

Death from uncontrolled haemorrhage is one of the leading causes of trauma-related mortality and is potentially preventable. Advances in understanding the mechanisms of trauma-induced coagulopathy (TIC) have focused attention on the role of blood products and procoagulants in mitigating the sequelae of TIC and how these therapies can be improved.

Recent findings

A host of preclinical and clinical studies have evaluated blood product availability and efficacy in trauma. Recently published randomized controlled trials have investigated the ratio of platelet:plasma:red cell transfusion and the role of early cryoprecipitate in trauma. Demand for readily available plasma has led to changes particularly in the use of thawed group A plasma. Furthermore, ex-vivo and early clinical work has demonstrated variations in the haemostatic activity of different plasma, platelet and whole blood products. A number of multicentre trials are in progress aiming to answer key questions regarding tranexamic acid, procoagulant factor and fibrinogen concentrates and their effect on trauma outcomes.

There are promising results from ex-vivo studies in manufacturing and storage of blood products to optimize haemostatic activity and availability, particularly with alternative plasma and platelet products and whole blood. There is an urgent need for these products needs to be tested prospectively.
The multitasking neutrophils and their involvement in angiogenesis
Authors: Seignez Cédric , Phillipson Mia
Published: October 2016

Purpose of review

This review describes the mechanisms by which neutrophils contribute to angiogenesis in hypoxic tissues during different conditions and diseases (e.g., menstrual cycle, wound healing, ischemic diseases, cancers), with particular focus on the recently described proangiogenic neutrophil subpopulation.

Recent findings

The importance of neutrophils in initiation of angiogenesis has been described during the past decade, and is believed to occur through release of the well-known proangiogenic factors Bv8, vascular endothelial growth factor A, and matrix metalloproteinase 9. However, additional proangiogenic actions of neutrophils have been outlined this year, mediated through for example pyruvate kinase M2, 14,15-epoxyeicosatrienoic acid, and formation of neutrophil extracellular traps, although their distinct mechanisms of action remain partly unknown. Neutrophils can also limit angiogenesis by secreting for example neutrophil elastase and α-defensins, which generate angiostatic molecules and proteolytically inactivate proangiogenic factors, respectively. These opposing neutrophil actions can be the consequence of on-site education or recruitment of distinct subpopulations from circulation. Indeed, a circulating proangiogenic neutrophil subpopulation was recently described in mice and men, which was rapidly recruited to hypoxic tissues by vascular endothelial growth factor A.

These recent findings have highlighted the diversity of actions performed by neutrophils in the angiogenic process and identified new opportunities to regulate angiogenesis.
Mechanism of granuloma formation in sarcoidosis
Authors: Sakthivel Priya , Bruder Dunja
Published: October 2016

Purpose of review

The formation of noncaseating granuloma is a hallmark of pulmonary sarcoidosis. This review summarizes recent progress made to explain the cellular dynamics within the granuloma structure that may considerably differ between the two clinically distinct variants, that is, acute and chronic sarcoidosis.

Recent findings

Compelling evidence exists that in acute but not chronic sarcoidosis CD4+ T lymphocytes specifically recognizing the auto-antigen vimentin on human leukocyte antigen-DR3 molecules accumulate in sarcoid granuloma. These so-called TH17.1 cells produce high amounts of the TH17-related cytokines interleukin-17 (IL-17) and IL-22 in addition to interferon-γ. Moreover, regulatory T cells from patients with acute sarcoidosis are ICOShigh, providing a mechanistic link to the comparably high concentration of IL-10 exclusively found in the airways of these patients. Next to obvious differences in T effector cell and Treg subsets, alveolar macrophages harbor a functional mitochondrial system in acute sarcoidosis patients, while this system is impaired in patients with chronic disease.

We provide a comprehensive update on the cellular components and their functional implications in sarcoid granuloma formation, with special emphasis on the specific characteristics of granuloma in acute versus chronic sarcoidosis. Moreover, the specific antigens thought to be involved in both forms of the disease are discussed.
Treatment of hemophagocytic lymphohistiocytosis
Authors: Wang Yini , Wang Zhao
Published: October 2016

Purpose of review

Hemophagocytic lymphohistiocytosis (HLH) is a condition of uncontrolled immune activation with a high mortality rate. The recommended therapeutic guideline for HLH was published by the Histiocyte Society in 1994 and revised in 2004, which greatly improved the survival in patients with HLH. However, HLH is still a refractory disease for which the search for novel treatments continues. This article overviewed recent advances in treatment of HLH.

Recent findings

Current practices in treatment extend from chemo-immunotherapy to some new cytokine-targeting biologicals, which are more effective to eliminate pathologically activated T cells and resist exaggerated cytokine storm. Preliminary results showed that some novel approaches to refractory HLH would potentially improve outcome of the fatal disease. Allogeneic hematopoietic stem cell transplantation after HLH remission represents the final solution for replacing defective cytotoxic T cells and even treating some underlying disease processes to prevent disease recurrence.

A uniform protocol and algorithm for the treatment would not be appropriate for each patient given the heterogeneity of the underlying conditions. Further improvements in therapy require prospective trials to develop reasonable strategies for HLH patients in different subtypes, based on the underlying trigger, disease severity, as well as genetic background.
Community-acquired pneumonia in the post 13-valent pneumococcal conjugate vaccine era
Authors: Shaughnessy Erin E. , Stalets Erika L. , Shah Samir S.
Published: October 2016

Purpose of review

This review covers the outpatient management of pediatric community-acquired pneumonia (CAP), discussing the changing microbiology of CAP since the introduction of the 13-valent pneumococcal conjugate vaccine in 2010, and providing an overview of national guideline recommendations for diagnostic evaluation and treatment.

Recent findings

Rates of invasive pneumococcal disease and pneumococcal antibiotic resistance have plummeted since widespread 13-valent pneumococcal conjugate vaccine immunization. Viruses remain the most common cause of CAP in young children; children over age 5 years have increased rates of Mycoplasma pneumoniae. A recent national guideline offers recommendations for office-based diagnostic evaluation and treatment of pediatric CAP.

This review offers a discussion of the above findings with practical recommendations for the office-based practitioner in the evaluation and treatment of an infant (>3 months) or child with suspected CAP.
Syphilis, hepatitis C and HIV in Eastern Europe
Authors: Bailey Heather , Turkova Anna , Thorne Claire
Published: October 2016

Purpose of review

Eastern Europe and Central Asia (EECA) has experienced large-scale epidemics of syphilis, hepatitis C virus (HCV) and HIV over the past few decades. Here, we review recent evidence on the epidemiology of and the response to these intersecting epidemics.

Recent findings

The HIV epidemic in EECA continues to expand, with new infections increasing by more than 50% between 2010 and 2015. HCV is now in the top 10 causes of death in EECA, with Russia accounting for more than half of the global burden of HCV infections, but access to direct-acting antivirals remains a major obstacle for control of the epidemic. Although syphilis incidence is generally declining, high prevalence is reported in key populations, particularly sex workers and people who inject drugs. Recent epidemiological studies have highlighted very high prevalence of HIV, syphilis and HCV in prison populations, alongside poor access to prevention and treatment.

Multiple factors are contributing to the ongoing and overlapping HIV, HCV and syphilis epidemics in EECA, including low coverage with antiretroviral therapy and insufficient scale of prevention services. Further research is required to estimate the burden of infections and identify effective prevention and treatment strategies in hard-to-reach key populations, particularly men who have sex with men.
Targeting the host immune system: PD-1 and PD-L1 antibodies and breast cancer
Authors: Dawood Shaheenah , Rugo Hope S.
Published: October 2016

Purpose of review

This article describes the role of the PD-1 axis and reviews current data and future directions inhibiting PD-1 and PD-L1 in breast cancer.

Recent findings

Four phase I monotherapy expansion trials in patients with metastatic breast cancer have demonstrated low but durable single agent responses to PD-1 and PD-L1 inhibitors, ranging from 4.8 to 19%. Higher response rates are seen in triple negative breast cancer, compared with hormone receptor positive disease. Variability in requirements for tumor PD-L1 expression, and variations in testing complicate cross trial comparisons. A fifth phase Ib trial reported a 38% response rate in metastatic triple negative breast cancer treated with the combination of a PD-L1 inhibitor and nab-paclitaxel chemotherapy. Treatment is generally well tolerated, with low rates of immune toxicity including hypothyroidism, pneumonitis, hepatitis, colitis, and hypophysitis, occurring even months after the end of therapy.

Immune checkpoint inhibitor therapy has recently been shown to have clinical efficacy in the treatment of breast cancer. The most compelling data are in the triple negative subtype, with responses documented in hormone receptor positive disease as well. Numerous trials are evaluating various combination strategies and biomarkers in early and late stage disease to enhance immunogenicity and response.
A Pilot Study of Randomized, Head-to-Head of Metformin Versus Topiramate in Obese People With Schizophrenia
Authors: Peng Po-Jui , Ho Pei-Shen , Tsai Chia-Kuang , Huang San-Yuan , Liang Chih-Sung
Published: October 2016

Objectives

A number of research studies support the weight loss effects of metformin and topiramate for obese people with schizophrenia. However, only a few studies have addressed the sustainability of the body weight reduction after discontinuation of these drugs. Moreover, head-to-head studies are still lacking. The study aims to evaluate and compare the efficacy of metformin and topiramate in weight reduction and weight maintenance after discontinuation of these drugs in obese people with schizophrenia.

Methods

Twenty-two obese inpatients with schizophrenia were recruited and randomized into the metformin group (n = 11; daily dose, 1000 mg) and the topiramate group (n = 11; daily dose, 100 mg). A head-to-head, fixed-dose, and single-blinded design was used. Ten obese patients with schizophrenia of similar sex as that of the treated group were included as the control group.

Results

After a 4-month treatment, the metformin group showed a body weight reduction of 3.8 kg, and the topiramate group showed a reduction of 2.7 kg. However, the reduction could be sustained only in the metformin group at 3 and 9 months after metformin discontinuation. Interestingly, 3 months after treatment discontinuation, leptin levels showed a reduction in both metformin (baseline, 25.3 ± 14.7, week 7: 5.7 ± 3.7 ng/mL) and topiramate (baseline: 28.4 ± 16.1, week 7: 9.2 ± 15.5 ng/mL) groups.

Conclusions

The trend of weight changes supports the superiority of metformin at 1000 mg/d over topiramate at 100 mg/d in weight reduction and weight maintenance.
How the European eel (
Anguilla anguilla
) loses its skeletal framework across lifetime
Authors: Rolvien Tim , Nagel Florian , Milovanovic Petar , Wuertz Sven , Marshall Robert Percy , Jeschke Anke , Schmidt Felix N. , Hahn Michael , Witten P. Eckhard , Amling Michael , Busse Björn
Published: October 2016

European eels (
Anguilla anguilla
) undertake an impressive 5 000 km long migration from European fresh waters through the North Atlantic Ocean to the Sargasso Sea. Along with sexual maturation, the eel skeleton undergoes a remarkable morphological transformation during migration, where a hitherto completely obscure bone loss phenomenon occurs. To unravel mechanisms of the maturation-related decay of the skeleton, we performed a multiscale assessment of eels' bones at different life-cycle stages. Accordingly, the skeleton reflects extensive bone loss that is mediated via multinucleated bone-resorbing osteoclasts, while other resorption mechanisms such as osteocytic osteolysis or matrix demineralization were not observed. Preserving mechanical stability and releasing minerals for energy metabolism are two mutually exclusive functions of the skeleton that are orchestrated in eels through the presence of two spatially segregated hard tissues: cellular bone and acellular notochord. The cellular bone serves as a source of mineral release following osteoclastic resorption, whereas the mineralized notochord sheath, which is inaccessible for resorption processes due to an unmineralized cover layer, ensures sufficient mechanical stability as a part of the notochord sheath. Clearly, an eel's skeleton is structurally optimized to meet the metabolic challenge of fasting and simultaneous sexual development during an exhausting journey to spawning areas, while the function of the vertebral column is maintained to achieve this goal.
Global population divergence and admixture of the brown rat (
Rattus norvegicus
)
Authors: Puckett Emily E. , Park Jane , Combs Matthew , Blum Michael J. , Bryant Juliet E. , Caccone Adalgisa , Costa Federico , Deinum Eva E. , Esther Alexandra , Himsworth Chelsea G. , Keightley Peter D. , Ko Albert , Lundkvist Åke , McElhinney Lorraine M. , Morand Serge , Robins Judith , Russell James , Strand Tanja M. , Suarez Olga , Yon Lisa , Munshi-South Jason
Published: October 2016

Native to China and Mongolia, the brown rat (
Rattus norvegicus
) now enjoys a worldwide distribution. While black rats and the house mouse tracked the regional development of human agricultural settlements, brown rats did not appear in Europe until the 1500s, suggesting their range expansion was a response to relatively recent increases in global trade. We inferred the global phylogeography of brown rats using 32 k SNPs, and detected 13 evolutionary clusters within five expansion routes. One cluster arose following a southward expansion into Southeast Asia. Three additional clusters arose from two independent eastward expansions: one expansion from Russia to the Aleutian Archipelago, and a second to western North America. Westward expansion resulted in the colonization of Europe from which subsequent rapid colonization of Africa, the Americas and Australasia occurred, and multiple evolutionary clusters were detected. An astonishing degree of fine-grained clustering between and within sampling sites underscored the extent to which urban heterogeneity shaped genetic structure of commensal rodents. Surprisingly, few individuals were recent migrants, suggesting that recruitment into established populations is limited. Understanding the global population structure of
R. norvegicus
offers novel perspectives on the forces driving the spread of zoonotic disease, and aids in development of rat eradication programmes.
Systematic Design and Comparison of Expanded Carrier Screening Panels
Authors: Beauchamp Kyle A. , Muzzey Dale , Wong Kenny K. , Hogan Gregory J. , Karimi Kambiz , Candille Sophie I. , Mehta Nikita , Mar-Heyming Rebecca , Kaseniit K. Eerik , Kang H. Peter , Evans Eric A. , Goldberg James D. , Lazarin Gabriel A. , Haque Imran S.
Published: October 2016

Purpose

The recent growth in pan-ethnic expanded carrier screening (ECS) has raised questions about how such panels might be designed and evaluated systematically. Design principles for ECS panels might improve clinical detection of at-risk couples and facilitate objective discussions of panel choice.

Methods

Guided by medical-society statements, we propose a method for the design of ECS panels that aims to maximize the aggregate and per-disease sensitivity and specificity across a range of Mendelian disorders considered serious by a systematic classification scheme. We evaluated this method retrospectively using results from 474,644 de-identified carrier screens. We then constructed several idealized panels to highlight strengths and limitations of different ECS methodologies.

Results

Based on modeled fetal risks for “severe” and “profound” diseases, a commercially available ECS panel (Counsyl) is expected to detect 183 affected conceptuses per 100,000 US births. A screen’s sensitivity is greatly impacted by two factors: (1) the methodology used (e.g., full-exon sequencing finds more affected conceptuses than targeted genotyping), and (2) the detection rate of the screen for diseases with high prevalence and complex molecular genetics (e.g., fragile X syndrome).

Conclusion

The described approaches allow principled, quantitative evaluation of which diseases and methodologies are appropriate for pan-ethnic expanded carrier screening.