bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of Distal Femur Nonunions Treated With a Combined Nail/Plate Construct and Autogenous Bone Grafting
Authors: Attum Basem , Douleh Diana , Whiting Paul S. , White-Dzuro Gabrielle A. , Dodd Ashley C. , Shen Michelle S. , Mir Hassan R. , Obremskey William T. , Sethi Manish K.
Published: July 2017

In this study, we sought to retrospectively evaluate union and infection rates after treatment of distal femur nonunions using a combined nail/plate construct with autogenous bone grafting obtained from the ipsilateral femur using a reamer irrigator aspirator system. Ten (10) patients treated at a Level I trauma center for nonunion of a femoral fracture using a combined nail/plate construct from 2004 to 2014 were included in the study. Union rate and postoperative infection rates were recorded. Mean interval from index surgery to nonunion repair was 12 months (range 4–36 months). Follow-up at 24 months indicated that the entire cohort of 10 patients achieved clinical union and radiographic union based on radiograph union score in tibias (RUST) criteria. Treatment of distal femur nonunions with a combined nail/plate construct and autogenous bone grafting results in a high rate of union with a low complication rate.
Treatment of Hyponatremic Encephalopathy in the Critically Ill
Authors: Achinger Steven G. , Ayus Juan Carlos
Published: July 2017

Objectives:

Hyponatremic encephalopathy, symptomatic cerebral edema due to a low osmolar state, is a medical emergency and often encountered in the ICU setting. This article provides a critical appraisal and review of the literature on identification of high-risk patients and the treatment of this life-threatening disorder.

Data Sources, Study Selection, and Data Extraction:

Online search of the PubMed database and manual review of articles involving risk factors for hyponatremic encephalopathy and treatment of hyponatremic encephalopathy in critical illness.

Data Synthesis:

Hyponatremic encephalopathy is a frequently encountered problem in the ICU. Prompt recognition of hyponatremic encephalopathy and early treatment with hypertonic saline are critical for successful outcomes. Manifestations are varied, depending on the extent of CNS’s adaptation to the hypoosmolar state. The absolute change in serum sodium alone is a poor predictor of clinical symptoms. However, certain patient specific risks factors are predictive of a poor outcome and are important to identify. Gender (premenopausal and postmenopausal females), age (prepubertal children), and the presence of hypoxia are the three main clinical risk factors and are more predictive of poor outcomes than the rate of development of hyponatremia or the absolute decrease in the serum sodium.

Conclusions:

In patients with hyponatremic encephalopathy exhibiting neurologic manifestations, a bolus of 100 mL of 3% saline, given over 10 minutes, should be promptly administered. The goal of this initial bolus is to quickly treat cerebral edema. If signs persist, the bolus should be repeated in order to achieve clinical remission. However, the total change in serum sodium should not exceed 5 mEq/L in the initial 1–2 hours and 15–20 mEq/L in the first 48 hours of treatment. It has recently been demonstrated in a prospective fashion that 500 mL of 3% saline at an infusion rate of 100 mL per hour can be given safely. It is critical to recognize the early signs of cerebral edema (nausea, vomiting, and headache) and intervene with IV 3% sodium chloride as this is the time to intervene rather than waiting until more severe symptoms develop. Cerebral demyelination is a rare complication of overly rapid correction of hyponatremia. The principal risk factors for cerebral demyelination are correction of the serum sodium more than 25 mEq/L in the first 48 hours of therapy, correction past the point of 140 mEq/L, chronic liver disease, and hypoxic/anoxic episode.
Wiesner Nevus of the Eyelid
Authors: Somogyi Marie , Lyons Lance J. , Durairaj Vikram
Published: July 2017

A healthy 31-year-old female presented with an elevated vascular lesion on the right lower eyelid margin. Histology results from excisional biopsy demonstrated a range of intradermally nested atypical melanocytes with negative staining for BRCA1-associated protein 1, confirming the diagnosis of Wiesner nevus. Wiesner nevi may be a cutaneous hallmark of the BRCA1-associated protein 1–associated cancer susceptibility syndrome, and to our knowledge, this is the first report of such a lesion presenting anywhere on the ocular adnexa.
Cytomegalovirus Infection in the Era of Preemptive Strategy in Allogeneic Hematopoietic Cell Transplant Recipients
Authors: Obeid Karam M. , Cober Eric , Abounader Donna , Gerds Aaron T. , Mossad Sherif B.
Published: July 2017

Objective

The aim of this study was to describe our experience with, and identify risk factors associated with, breakthrough cytomegalovirus disease (CMVD) in allogeneic hematopoietic stem cell transplant during regular monitoring and preemptive therapy for CMV viremia.

Methods

This was a retrospective study comparing allogeneic hematopoietic stem cell transplant recipients who developed CMVD despite a preemptive treatment strategy to patients with CMV viremia without CMVD.

Results

Of 104 recipients transplanted at a single institution, who developed CMV viremia and/or disease, we identified 15 cases of biopsy-proven CMVD and 74 recipients with CMV viremia alone; 30 of 74 were included as control subjects after appropriate surveillance. The rate of CMVD was low at 5%. While patients are monitored for CMV viremia, CMVD was the presenting manifestation of CMV infection in the majority of cases (60%), and 40% did not have viremia at the time of diagnosis. No one risk factor predicted CMVD. Patients with CMVD tended to have high-risk CMV serostatus, moderate to severe graft-versus-host disease, and to have higher mortality rate.

Conclusions

Preemptive strategy with targeted therapy to patients with CMV viremia is effective with rare and unpredictable events of breakthrough CMVD. Patients with high-risk CMV serostatus and moderate to severe graft-versus-host disease may need more vigilant observation. Cytomegalovirus disease may occur without viremia requiring close monitoring for symptoms suggestive of CMVD.
Diverticulitis in the Neutropenic Patient
Authors: Vellanki Meghana , Sethi Sajiv , Nanjappa Sowmya , Greene John N.
Published: July 2017

Diverticulitis is a common gastrointestinal disease; however, it is rarely described in patients with immunosuppression. Neutropenic patients who present with fever and gastrointestinal symptoms such as abdominal pain, diarrhea, and rectal bleeding are suspected to have Clostridium difficile colitis or typhlitis. However, a third possibility, diverticulitis, should be considered and can lead to complications of perforation and sepsis. Acute diverticulitis in the setting of neutropenia is rarely reported in the literature. We present 2 cases of diverticulitis in neutropenic patients with acute myeloid leukemia.
Impact of Antimicrobial Stewardship Consultation Service at an Academic Institution
Authors: Suleyman Geehan , Grunwald Jenny , Kenney Rachel M. , Davis Susan L. , Zervos Marcus J. , Weinmann Allison
Published: July 2017

Background

Antimicrobial stewardship programs (ASPs) aim to optimize antimicrobial use to decrease resistance and acquisition of hospital-acquired infections, improve patient outcomes, and reduce health care costs. We evaluated interventions and outcomes associated with a dedicated stewardship consult service staffed by physician assistant with supervision from infectious disease physician.

Methods

This was a retrospective study of electronic medical records of adult patients evaluated by the ASP team from November 2012 to December 2013 in an 802-bed teaching hospital in Detroit, Mich. Hospice patients were excluded. Patient characteristics, type of infection, microbiological cultures, antimicrobials utilized, interventions performed, and clinical outcomes were assessed.

Results

Three hundred thirty-five patients met the inclusion criteria. Median age was 67 years, and 52% were male. The most common infections were lower respiratory (28%) and urinary tract infections (21%). However, 24% were diagnosed as having no infection, and of these, 67% had asymptomatic bacteriuria. Escherichia coli (21%) and methicillin-resistant Staphylococcus aureus (14%) were most frequently isolated pathogens. The ASP team denied 38% of peripherally inserted central catheter requests and recommended intravenous-to-oral conversion in 38% cases, discontinuation of antibiotics in 27%, and de-escalation of therapy in 13%. Vancomycin (18%) and quinolones (16%) were the most commonly prescribed antibiotics. The majority of patients (95%) had clinical success, whereas very few developed Clostridium difficile infection (1.5%) or had infection-related readmission (2%) within 30 days.

Conclusions

Our ASP consult service reduced unnecessary peripherally inserted central catheter placement and antimicrobial use with favorable clinical success and patient outcomes. In light of the new regulatory ASP requirements, a midlevel provider may be beneficial to and an integral part of an infectious disease physician-supervised stewardship team.
Presumptive Treatment of Chlamydia and Gonorrhea Infections in a Canadian Ambulatory Emergency Department Setting
Authors: Friedland Sayuri N. , Slapcoff Barry , Dylewski Joe
Published: July 2017

Objectives

Presumptive antibiotic treatment may be given for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) infections before a laboratory diagnosis is established, but overtreatment can increase resistance rates. We sought to determine the presumptive treatment prevalence in our emergency department (ED) setting, as well as the number of overtreated and undertreated patients.

Methods

We performed a retrospective cohort study of all patients tested for CT/GC in an urban academic ED during a 6-month period in 2015. Presumptive treatment prevalence, overtreatment and undertreatment proportions, and CT- and GC-positive test proportions were calculated with 95% Wald confidence interval (CI) and compared across age and sex.

Results

Of 209 included cases (male n = 3, female n = 206), 27 (13%; CI, 8%–18%) received presumptive treatment for CT and 19 (9%; CI, 5%–14%) for GC. Seven cases (3%; CI, 1%–6%) were positive for CT and 0 for GC. Of the 7 CT-positive cases, 2 (29%) received presumptive treatment in the ED, and 5 (71%) were treated after the positive test results were obtained. There was no loss to follow-up. Mean delay to treatment was 10 days, including a mean of 3 days for laboratory analysis. Overtreatment and undertreatment proportions were 93% (CI, 83%–100%) and 3% (CI, 0%–5%) for CT and 100% and 0% for GC, respectively. Positive test result, presumptive treatment, overtreatment, and undertreatment were not associated with age or sex.

Conclusions

Given the low CT/GC incidence and good follow-up, at our institution, it would be reasonable to wait for a laboratory diagnosis rather than give presumptive treatment.
Cognitive load selectively influences the interruptive effect of pain on attention
Authors: Moore David J. , Eccleston Christopher , Keogh Edmund
Published: July 2017

Pain is known to interrupt attentional performance. Such interference effects seem to occur preferentially for tasks that are complex and/or difficult. However, few studies have directly manipulated memory load in the context of pain interference to test this view. Therefore, this study examines the effect of experimental manipulations of both memory load and pain on 3 tasks previously found to be sensitive to pain interference. Three experiments were conducted. A different task was examined in each experiment, each comprising of a high- and low-cognitive load versions of the task. Experiment 1 comprised an attention span (n-back) task, experiment 2 an attention switching task, and experiment 3 a divided attention task. Each task was conducted under painful and nonpainful conditions. Within the pain condition, an experimental thermal pain induction protocol was administered at the same time participants completed the task. The load manipulations were successful in all experiments. Pain-related interference occurred under the high-load condition but only for the attention span task. No effect of pain was found on either the attentional switching or divided attention task. These results suggest that while cognitive load may influence the interruptive effect of pain on attention, this effect may be selective. Because pain affected the high-load version of the n-back task but did not interrupt performance on attentional switching or dual-task paradigms, this means that our findings did not completely support our hypotheses. Future research should explore further the parameters and conditions under which pain-related interference occurs.
Nurse Perspective on Delusions of Parasitosis
Authors: Boghosian Gayle , Johnson Cassandra , Jacob Sharon E.
Published: July 2017

Dermatology is a complex area of medicine that requires knowledge of skin biology, pathophysiology, chemistry, diagnostic tests, and physical examination. Although the skin may be the primary focus of a disease process, systemic disease processes may present with manifestation in the skin. This nurse perspective focuses on delusions of parasitosis or Ekbom’s syndrome. Ekbom’s syndrome is a psychocutaneous disorder in which patients believe they are infested with bugs, in the absence of actual infestation. This disorder needs multidisciplinary collaboration to aid treatment.
Noncontrast Hybrid Arterial Spin-Labeled Imaging of the Intracranial Arteries
Authors: Lim Ruth P. , Trajcevska Elena , Al Rawi Farah , Gooneratne Dinesh , Ang Windell , Perchyonok Yuliya , Fitt Gregory , Kemp Andrew , Giri Shivraman , Piccini Davide , Brodtmann Amy , Dewey Helen , Koktzoglou Ioannis
Published: July 2017

Objective

The purpose of this study is to evaluate feasibility, image quality (IQ), and accuracy of noncontrast hybrid arterial spin labeling (NoHASL) magnetic resonance angiography (MRA) compared with time of flight (TOF) MRA and contrast-enhanced (CE) MRA in patients with known/suspected cerebrovascular ischemia.

Methods

Thirty inpatients were imaged at 1.5 T. Two neuroradiologists assessed 630 intracranial arterial segments for IQ (1, nondiagnostic; 3, satisfactory for diagnosis; and 5, excellent). Hemodynamically significant stenosis (>50%) was assessed against all combined techniques as reference.

Results

The NoHASL MRA IQ was diagnostic (3.32 ± 0.86) but affected by signal to noise ratio and spatial resolution limitations and significantly inferior to TOF (3.48 ± 0.68) and CE MRA (3.44 ± 0.78) (P < 0.0001 in both comparisons). Fourteen (2.2%) of 630 segments had hemodynamically significant stenoses at the reference standard. Sensitivity/specificity was not significantly different between techniques: NoHASL MRA, 67.9%/90.0%; TOF MRA, 67.9%/97.7%; and CE MRA, 50.0%/98.7%.

Conclusions

The NoHASL MRA is feasible, with diagnostic quality imaging of proximal intracranial vessels. Low disease prevalence limited the assessment of technique accuracy.
Urinary Macrophage Migration Inhibitory Factor as a Noninvasive Biomarker in Pediatric Henoch-Schönlein Purpura Nephritis
Authors: Wang Jiapei , Li Yunyan , Chen Yuanling , Dai Xiahua , Di Yazhen , Shen Mengjiao , Ying Qianqian , Fu Shiwei , Li Yinjie
Published: July 2017

Purposes

The aims of this study were to investigate urinary macrophage migration inhibitory factor (MIF) levels and their clinical significance in Henoch-Schönlein purpura (HSP) children with or without nephritis (N) and to assess the influence of steroid treatment on the urine MIF levels of HSPN patients.

Methods

Group I comprised 35 children with HSPN who were examined twice (A before treatment and B after steroid treatment). Group II comprised 41 children with HSP. The control group included 32 healthy children. Urinary MIF levels were measured via enzyme linked immunosorbent assay. The levels of serum creatinine, blood urea nitrogen, urinary microalbumin (mAlb), and 24-hour proteinuria were performed to determine their associations with MIF levels.

Results

Urinary MIF levels were significantly higher in group I compared with group II and the control group (P < 0.01); however, no significant difference was found between group II and the control group (P > 0.05). Upon examination, albeit urinary MIF concentration was significantly lower in group IB compared with group IA (P < 0.05), these concentrations were statistically higher than that of group II (P < 0.05). In addition, in the HSPN patients, the urinary MIF was positively associated with urinary microalbumin and 24-hour proteinuria but no association with serum creatinine and blood urea nitrogen.

Conclusions

Elevated urinary MIF levels were found to be correlated with proteinuria in pediatric HSPN. An obvious decrease in urinary MIF concentrations among the children with HSPN was associated with steroid treatment. Urinary MIF can be used as a noninvasive biomarker in pediatric HSPN.
Probabilistic stability analysis: the way forward for stability analysis of sustainable power systems
Authors: Milanović Jovica V.
Published: July 2017

Future power systems will be significantly different compared with their present states. They will be characterized by an unprecedented mix of a wide range of electricity generation and transmission technologies, as well as responsive and highly flexible demand and storage devices with significant temporal and spatial uncertainty. The importance of probabilistic approaches towards power system stability analysis, as a subsection of power system studies routinely carried out by power system operators, has been highlighted in previous research. However, it may not be feasible (or even possible) to accurately model all of the uncertainties that exist within a power system. This paper describes for the first time an integral approach to probabilistic stability analysis of power systems, including small and large angular stability and frequency stability. It provides guidance for handling uncertainties in power system stability studies and some illustrative examples of the most recent results of probabilistic stability analysis of uncertain power systems.

This article is part of the themed issue ‘Energy management: flexibility, risk and optimization’.
Robust estimation of risks from small samples
Authors: Tindemans Simon H. , Strbac Goran
Published: July 2017

Data-driven risk analysis involves the inference of probability distributions from measured or simulated data. In the case of a highly reliable system, such as the electricity grid, the amount of relevant data is often exceedingly limited, but the impact of estimation errors may be very large. This paper presents a robust non-parametric Bayesian method to infer possible underlying distributions. The method obtains rigorous error bounds even for small samples taken from ill-behaved distributions. The approach taken has a natural interpretation in terms of the intervals between ordered observations, where allocation of probability mass across intervals is well specified, but the location of that mass within each interval is unconstrained. This formulation gives rise to a straightforward computational resampling method: Bayesian interval sampling. In a comparison with common alternative approaches, it is shown to satisfy strict error bounds even for ill-behaved distributions.

This article is part of the themed issue ‘Energy management: flexibility, risk and optimization’.
Real option valuation of a decremental regulation service provided by electricity storage
Authors: Szabó Dávid Zoltán , Martyr Randall
Published: July 2017

This paper is a quantitative study of a reserve contract for real-time balancing of a power system. Under this contract, the owner of a storage device, such as a battery, helps smooth fluctuations in electricity demand and supply by using the device to increase electricity consumption. The battery owner must be able to provide immediate physical cover, and should therefore have sufficient storage available in the battery before entering the contract. Accordingly, the following problem can be formulated for the battery owner: determine the optimal time to enter the contract and, if necessary, the optimal time to discharge electricity before entering the contract. This problem is formulated as one of optimal stopping, and is solved explicitly in terms of the model parameters and instantaneous values of the power system imbalance. The optimal operational strategies thus obtained ensure that the battery owner has positive expected economic profit from the contract. Furthermore, they provide explicit conditions under which the optimal discharge time is consistent with the overall objective of power system balancing. This paper also carries out a preliminary investigation of the ‘lifetime value’ aggregated from an infinite sequence of these balancing reserve contracts. This lifetime value, which can be viewed as a single project valuation of the battery, is shown to be positive and bounded. Therefore, in the long run such reserve contracts can be beneficial to commercial operators of electricity storage, while reducing some of the financial and operational risks in power system balancing.

This article is part of the themed issue ‘Energy management: flexibility, risk and optimization’.
SPATA2 regulates the activation of RIPK1 by modulating linear ubiquitination
Authors: Wei Ran , Xu Lily Wen , Liu Jianping , Li Yanxia , Zhang Pei , Shan Bing , Lu Xiaojuan , Qian Lihui , Wu Zheming , Dong Kangyun , Zhu Hong , Pan Lifeng , Yuan Junying , Pan Heling
Published: July 2017

Stimulation of cells with TNFα leads to the formation of the TNF-R1 signaling complex (TNF-RSC) to mediate downstream cellular fate decision. Activation of the TNF-RSC is modulated by different types of ubiquitination and may lead to cell death, including apoptosis and necroptosis, in both RIPK1-dependent and RIPK1-independent manners. Spata2 (spermatogenesis-associated 2) is an adaptor protein recruited into the TNF-RSC to modulate the interaction between the linear ubiquitin chain assembly complex (LUBAC) and the deubiquitinase CYLD (cylindromatosis). However, the mechanism by which Spata2 regulates the activation of RIPK1 is unclear. Here, we report that Spata2-deficient cells show resistance to RIPK1-dependent apoptosis and necroptosis and are also partially protected against RIPK1-independent apoptosis. Spata2 deficiency promotes M1 ubiquitination of RIPK1 to inhibit RIPK1 kinase activity. Furthermore, we provide biochemical evidence for the USP domain of CYLD and the PUB domain of the SPATA2 complex preferentially deubiquitinating the M1 ubiquitin chain in vitro. Spata2 deficiency also promotes the activation of MKK4 and JNK and cytokine production independently of RIPK1 kinase activity. Spata2 deficiency sensitizes mice to systemic inflammatory response syndrome (SIRS) induced by TNFα, which can be suppressed by RIPK1 inhibitor Nec-1s. Thus, Spata2 can regulate inflammatory response and cell death in both RIPK1-dependent and RIPK1-independent manners.
Brexit and Parliamentary Sovereignty
Authors: Ewing Keith
Published: July 2017

This note addresses the implications of R (Miller) v Secretary of State for Exiting the European Union for the legal principle of parliamentary sovereignty, and argues that the strong restatement of the latter is the most significant feature of the decision. The aim here is to show how traditional principle in the Dicey tradition has been strongly applied against the competing claims of EU law, the royal prerogative, the referendum and devolution. However, the note also argues that the claims relating to parliamentary sovereignty could have produced a different result and that the most compelling feature of the case was the argument that was not forcefully put by the Government, namely that Parliament had already provided sufficient authority for the triggering of Article 50.
Gender, ethnicity and smoking affect pain and function in patients with rotator cuff tears
Authors: Maher Anthony , Leigh Warren , Brick Matt , Young Simon , Millar James , Walker Cameron , Caughey Michael
Published: July 2017

Background

This study is a collation of baseline demographic characteristics of those presenting for rotator cuff repair in New Zealand, and exploration of associations with preoperative function and pain. Data were obtained from the New Zealand Rotator Cuff Registry; a multicentre, nationwide prospective cohort of rotator cuff repairs undertaken from 1 March 2009 until 31 December 2010.

Methods

A total of 1383 patients were included in the study. This required complete demographic information, preoperative Flex‐SF (functional score) and pain scores. Following univariate analysis, a multivariate model was used.

Results

The average age was 58 years (69% males and 11% smokers). New Zealand Europeans made up 90% and Maori 5%. The average preoperative Flex‐SF was significantly lower (poorer function) in those over 65 years, females, smokers and Maori, in the non‐dominant patients, using a multivariate model. Average preoperative pain scores were significantly worse (higher scores) in females, Maori, Polynesians, smokers, using a multivariate model.

Conclusion

This is the largest reported prospective cohort of patients presenting for rotator cuff surgery. Results can be used to understand the effect of rotator cuff tears on the different patients, for example Maori patients who are under‐represented, present younger, with more pain and poorer function.
Data Abstraction for Visualizing Large Time Series
Authors: Shurkhovetskyy G. , Andrienko N. , Andrienko G. , Fuchs G.
Published: July 2017

Numeric time series is a class of data consisting of chronologically ordered observations represented by numeric values. Much of the data in various domains, such as financial, medical and scientific, are represented in the form of time series. To cope with the increasing sizes of datasets, numerous approaches for abstracting large temporal data are developed in the area of data mining. Many of them proved to be useful for time series visualization. However, despite the existence of numerous surveys on time series mining and visualization, there is no comprehensive classification of the existing methods based on the needs of visualization designers. We propose a classification framework that defines essential criteria for selecting an abstraction method with an eye to subsequent visualization and support of users' analysis tasks. We show that approaches developed in the data mining field are capable of creating representations that are useful for visualizing time series data. We evaluate these methods in terms of the defined criteria and provide a summary table that can be easily used for selecting suitable abstraction methods depending on data properties, desirable form of representation, behaviour features to be studied, required accuracy and level of detail, and the necessity of efficient search and querying. We also indicate directions for possible extension of the proposed classification framework.
Five Methods for Estimating Angoff Cut Scores with IRT
Authors: Wyse Adam E.
Published: July 2017

This article illustrates five different methods for estimating Angoff cut scores using item response theory (IRT) models. These include maximum likelihood (ML), expected a priori (EAP), modal a priori (MAP), and weighted maximum likelihood (WML) estimators, as well as the most commonly used approach based on translating ratings through the test characteristic curve (i.e., the IRT true‐score (TS) estimator). The five methods are compared using a simulation study and a real data example. Results indicated that the application of different methods can sometimes lead to different estimated cut scores, and that there can be some key differences in impact data when using the IRT TS estimator compared to other methods. It is suggested that one should carefully think about their choice of methods to estimate ability and cut scores because different methods have distinct features and properties. An important consideration in the application of Bayesian methods relates to the choice of the prior and the potential bias that priors may introduce into estimates.
The role of experiential knowledge within attitudes towards genetic carrier screening: A comparison of people with and without experience of spinal muscular atrophy
Authors: Boardman Felicity K. , Young Philip J. , Warren Oliver , Griffiths Frances E.
Published: July 2017

Purpose

Autosomal recessive conditions, while individually rare, are a significant health burden with limited treatment options. Population carrier screening has been suggested as a means of tackling them. Little is known, however, about the attitudes of the general public towards such carrier screening and still less about the views of people living with candidate genetic diseases. Here, we focus on the role that such experience has on screening attitudes by comparing views towards screening of people with and without prior experience of the monogenetic disorder, Spinal Muscular Atrophy.

Methods

An exploratory sequential mixed methods design was adopted. In‐depth qualitative interviews were used to develop two surveys. The surveys addressed attitudes towards carrier screening (pre‐conceptual and prenatal) for SMA.

Participants

337 participants with SMA experience completed the SMA Screening Survey (UK) and 336 participants with no prior experience of SMA completed the UK GenPop Survey, an amended version of the SMA Screening Survey (UK).

Results

The majority of both cohorts were in favour of pre‐conception and prenatal carrier screening, however people with experience of type II SMA were least likely to support either. Key differences emerged around perceptions of SMA, with those without SMA experience taking a dimmer view of the condition than those with.

Conclusion

This study underscores the significance of prior experience with the condition to screening attitudes. It highlights the need for accurate and high‐quality educational resources to support any future carrier screening programmes, that particularly in relation to rare genetic disorders like SMA that will fall outside the remit of everyday experience for the majority of the population.
Week 96 results of the randomized, multicentre Maraviroc Switch (MARCH) study
Authors: Pett SL , Amin J , Horban A , Andrade‐Villanueva J , Losso M , Porteiro N , Madero JS , Belloso W , Tu E , Silk D , Kelleher A , Harrigan R , Clark A , Sugiura W , Wolff M , Gill J , Gatell J , Clarke A , Ruxrungtham K , Prazuck T , Kaiser R , Woolley I , Alberto Arnaiz J , Cooper D , Rockstroh JK , Mallon P , Emery S ,   the MARCH study group
Published: July 2017

Objectives

The Maraviroc Switch (MARCH) study week 48 data demonstrated that maraviroc, a chemokine receptor‐5 (CCR5) inhibitor, was a safe and effective switch for the ritonavir‐boosted protease inhibitor (PI/r) component of a two nucleos(t)ide reverse transcriptase inhibitor [N(t)RTI] plus PI/r‐based antiretroviral regimen in patients with R5‐tropic virus. Here we report the durability of this finding.

Methods

MARCH, an international, multicentre, randomized, 96‐week open‐label switch study, enrolled HIV‐1‐infected adults with R5‐tropic virus who were stable (> 24 weeks) and virologically suppressed [plasma viral load (pVL) < 50 HIV‐1 RNA copies/mL]. Participants were randomized to continue their current PI/r‐based regimen (PI/r) or to switch to MVC plus two N(t)RTIs (MVC) (1:2 randomization). The primary endpoint was the difference in the proportion with pVL < 200 copies/mL at 96 weeks. The switch arm was defined as noninferior if the lower limit of the 95% confidence interval (CI) for the difference was < −12% in the intention‐to‐treat (ITT) population. Safety endpoints (the difference in the mean change from baseline or a comparison of proportions) were analysed as key secondary endpoints.

Results

Eighty‐two (PI/r) and 156 (MVC) participants were randomized and included in the ITT analysis; 71 (87%) and 130 (83%) were in follow‐up and on therapy at week 96. At week 96, 89.0% and 90.4% in the PI/r and MVC arms, respectively, had pVL < 50 copies/mL (95% CI ‐6.6, 10.2). Moreover, in those switching away from PI/r, there were significant reductions in mean total cholesterol (differences 0.31 mmol/L; P = 0.02) and triglycerides (difference 0.44 mmol/L; P < 0.001). Changes in CD4 T‐cell count, renal function, and serious and nonserious adverse events were similar in the two arms.

Conclusions

MVC as a switch for a PI/r is safe and effective at maintaining virological suppression while having significant lipid benefits over 96 weeks.
Analysis of cytochrome P450 contribution to evolved plant toxin resistance inDrosophila sechellia
Authors: Peyser R. D. , Lanno S. M. , Shimshak S. J. , Coolon J. D.
Published: July 2017

Drosophila sechelliais a dietary specialist species of fruit fly that has evolved resistance to the toxic secondary defence compounds produced by the fruit of its preferred host plantMorinda citrifolia. The genetic basis of adult toxin resistance is the result of evolution at five loci across the genome. Genetic mapping betweenD. sechelliaandDrosophila simulansand subsequent functional studies inDrosophila melanogasterhave identified candidate genes potentially underlying one locus involved in toxin resistance but the remainder of the genes involved are unknown. Genes in the mixed function oxidase or cytochrome P450 gene family are frequently utilized in evolved toxin resistance in insects, yet whether they play a role inD. sechellia's resistance to the toxins found in its host plant is unknown. Here we test the role of cytochrome P450 enzymatic activity in evolved resistance to the two primary toxins found inM. citrifoliafruit: octanoic acid and hexanoic acid. We found that although cytochrome P450 enzymatic activity is involved in basal resistance it is not involved in derived toxin resistance inD. sechellia.
Professional oral health care for preventing nursing home‐acquired pneumonia: A cost‐effectiveness and value of information analysis
Authors: Schwendicke Falk , Stolpe Michael , Müller Frauke
Published: July 2017

Aim

Professional oral health care (POHC) prevents nursing home‐acquired pneumonia (NHAP) and its related mortality. We assessed the cost‐effectiveness of POHC versus no POHC (nPOHC) and the monetary value of eliminating uncertainty by future research.

Methods

A German public–private payer perspective was adopted. A Markov model was used, following long‐term care residents from admission to death. Cost‐effectiveness was estimated as Euro/disability‐adjusted life year (DALY) using Monte Carlo microsimulations. Value‐of‐information analyses were performed. The willingness‐to‐pay threshold/DALY was assumed to be 66% (range 50%–100%) of per‐capita gross domestic product (GDP).

Results

nPOHC was less costly (€3,024) but also less effective (0.89 DALYs) than POHC (€10,249, 0.55 DALYs). For most presumed payers, POHC was cost‐effective. The cost‐effectiveness of POHC was higher in smokers, underweight or pulmonary disease patients. Eliminating uncertainty about the NHAP costs, NHAP incidence/mortality, and POHC effectiveness would result in an expected net value of 47 million €/year (and even higher values at lower GDP thresholds), and is likely to decrease with time.

Conclusions

Within the chosen setting and on the basis of current evidence, POHC was cost‐effective. Given the detected uncertainty, further research seems warranted.
Bone tissue response following local drug delivery of bisphosphonate through titanium oxide nanotube implants in a rabbit model
Authors: Kwon David H. , Lee Sang J. , Wikesjö Ulf M. E. , Johansson Petra H. , Johansson Carina B. , Sul Young‐Taeg
Published: July 2017

Objectives

The objective of this study was to evaluate whether surface chemistry‐controlled TiO2 nanotube structures may serve as a local drug delivery system for zoledronic acid improving implant‐bone support.

Methods

Twenty‐four screw‐shaped Ti implants with surface chemistry‐controlled TiO2 nanotube structures were prepared and divided into a zoledronic acid‐formatted test and a native control group. The implants were inserted into contra‐lateral femoral condyles in 12 New Zealand White rabbits. Bone support was evaluated using resonance frequency analysis (RFA) and removal torque (RTQ), as well as histometric analysis following a 3‐weeks healing interval.

Results

Zoledronic acid‐formatted TiO2 nanotube test implants showed significantly improved implant stability and osseointegration measured using RFA and RTQ compared with control (p < 0.05), and showed significantly enhanced new bone formation within the root of the threads compared with control (p < 0.05).

Conclusions

TiO2 nanotube implants may prove to be a significant delivery system for drugs or biologic agents aimed at supporting local bone formation. Additional study of candidate drugs/agents, optimized dosage and release kinetics is needed prior to evaluation in clinical settings.
Reconstruction of 3D grain boundaries from rock thin sections, using an advanced polarised‐light microscopy method
Authors: HAMMES D.M. , PETERNELL M.
Published: July 2017

Grain boundaries play a significant role in materials by initiating reactions and collecting impurities. Here we present FAGO (Fabric Analyser Grain boundary recOnstruction), a first step towards the automatic determination of three‐dimensional (3D) grain boundary geometry using polarised light. The trace of the grain boundaries from 2D rock thin sections are determined primarily from data acquired using an automatic fabric analyser microscope and the FAME software (fabric analyser‐based microstructure evaluation; Peternell and colleagues and Hammes and Peternell). Based on the Fabric Analyser G50's unique arrangement of nine differently oriented light sources the retardation can be determined independently for each light direction and at each pixel in the field of view. FAGO combines these retardation datasets for each individual pixel together with retardation profiles across grain boundaries, to determine the orientations of the boundaries. The grain boundary traces are then broken up into segments of equal orientation, using the profile‐obtained orientation data. Finally, a 3D grain boundary model is reconstructed. The data processing is almost fully automatic using the MATLAB® environment. Only minor manual inputs are required.
Biochemical and hematological evaluations of black howler monkeys (Alouatta pigra) in highly degraded landscapes in Mexico
Authors: García‐Feria Luis M. , Chapman Colin A. , Pastor‐Nieto Rosalía , Serio‐Silva Juan Carlos
Published: July 2017

Background

Loss and fragmentation of Neotropical primates’ habitat can alter the health and individual adaptation. Physiological parameters reflect health status and individuals responses to the habitat conditions.

Methods

We captured six wild adult females and six adult males of Alouatta pigra to evaluate their physical condition (body mass, respiratory and heart rate, and rectal temperature), hematology and blood chemistry on fragmentation habitat condition at southeastern Mexico.

Results

The males weighed more than females, but the female’ temperature, respiratory rate, and heart rate were higher. Low values of hemoglobin, hematocrit, and red blood cells suggest some degree of anemia in these howler monkeys. Low levels of the total protein, albumin, albumin/globulin Ratio, and low levels of blood urea nitrogen suggest that howler monkeys could have protein and carbohydrate deficiencies.

Conclusions

Howler monkeys living under the highly degraded conditions at Balancán, Tabasco, could be showing adaptability by modifying their physiology, hematology, and blood chemistry in response to the conditions of their fragmented landscape.
Non‐decoupled morphological evolution of the fore‐ and hindlimb of sabretooth predators
Authors: Martín‐Serra Alberto , Figueirido Borja , Palmqvist Paul
Published: July 2017

Specialized organisms are useful for exploring the combined effects of selection of functional traits and developmental constraints on patterns of phenotypic integration. Sabretooth predators are one of the most interesting examples of specialization among mammals. Their hypertrophied, sabre‐shaped upper canines and their powerfully built forelimbs have been interpreted as adaptations to a highly specialized predatory behaviour. Given that the elongated and laterally compressed canines of sabretooths were more vulnerable to fracture than the shorter canines of conical‐tooth cats, it has been long hypothesized that the heavily muscled forelimbs of sabretooths were used for immobilizing prey before developing a quick and precise killing bite. However, the effect of this unique adaptation on the covariation between the fore‐ and the hindlimb has not been explored in a quantitative fashion. In this paper, we investigate if the specialization of sabretooth predators decoupled the morphological variation of their forelimb with respect to their hindlimb or, in contrast, both limbs vary in the same fashion as in conical‐tooth cats, which do not show such extreme adaptations in their forelimb. We use 3D geometric morphometrics and different morphological indices to compare the fore‐ and hindlimb of conical‐ and sabretooth predators. Our results indicate that the limb bones of sabretooth predators covary following the same trend of conical‐tooth cats. Therefore, we show that the predatory specialization of sabretooth predators did not result in a decoupling of the morphological evolution of their fore‐ and hindlimbs. The role of developmental constraints and natural selection on this coordinate variation between the fore‐ and the hindlimb is discussed in the light of this new evidence.
HBV reactivation in patients with HCV/HBV cirrhosis on treatment with direct‐acting antivirals
Authors: Calvaruso V. , Ferraro D. , Licata A. , Bavetta M. G. , Petta S. , Bronte F. , Colomba G. , Craxì A. , Di Marco V.
Published: July 2017

Anecdotal reports suggest that patients with chronic hepatitis C virus (HCV) hepatitis and overt or occult hepatitis B virus (HBV) coinfection may reactivate HBV when HCV is suppressed or cleared by direct‐acting antivirals (DAAs). We assessed the prevalence of overt or previous HBV coinfection and the risk of HBV reactivation in patients with HCV cirrhosis treated with DAAs. This was a retrospective cohort of 104 consecutive patients with HCV cirrhosis treated with DAAs. Serum HCV‐RNA and HBV‐DNA were tested at weeks 4, 8 and 12 of DAAs therapy and at week 12 of follow‐up. At the start of DAAs, eight patients (7.7%) were HBsAg positive/HBeAg negative with undetectable HBV‐DNA and low levels of quantitative HBsAg (four on nucleos(t)ide analogues [NUCs] and four inactive carriers), 37 patients (35.6%) had markers of previous HBV infection (25 anti‐HBc positive, 12 anti‐HBc/anti‐HBs positive) and 59 (56.7%) had no evidence of HBV infection. Sixty‐seven patients (64.4%) were HCV‐RNA negative at week 4 and 98 (94.2%) achieved sustained virological response. All four HBsAg‐positive patients treated with NUCs remained HBV‐DNA negative, but three of four untreated patients showed an increase in HBV‐DNA of 2‐3 log without a biochemical flare and achieved HBV‐DNA suppression when given NUCs. During or after DAAs, by conventional assay, HBV‐DNA remained not detectable in all 37 anti‐HBc‐positive patients but in three of them (8.1%) HBV‐DNA became detectable with a highly sensitive PCR. HBV reactivation is likely to occur in untreated HBV/HCV‐coinfected cirrhotic patients when they undergo HCV treatment with DAAs. Pre‐emptive therapy with NUCs should be considered in this setting. Anti‐HBc‐positive patients rarely reactivate HBV without clinical or virological outcomes.
Review of some pharmacokinetic and pharmacodynamic properties of anti‐infective medicines administered to the koala (Phascolarctos cinereus)
Authors: Govendir M.
Published: July 2017

Although koalas are iconic Australian animals, no pharmacokinetic studies of any first‐line medicines used to treat diseased or injured koalas had been published prior to 2010. Traditionally, medicine dosages suggested for this species underwent linear extrapolation from those recommended for domesticated species. The koala, a specialist folivore whose natural diet consists of almost exclusivelyEucalyptusspp. foliage has anatomical and physiological adaptations for detoxifying their diet which also affect medicine pharmacokinetic profiles. This review addresses aspects of medicine absorption, clearance, and other indices (such as medicine binding to plasma proteins) of enrofloxacin/marbofloxacin and chloramphenicol used for the systemic treatment of chlamydiosis, and fluconazole ± amphotericin, and posaconazole for the treatment of cryptococcosis. Based on observations from published studies, this review includes suggestions to improve therapeutic outcomes when administering medicines to diseased koalas.
Bargaining and Wage Rigidity in a Matching Model for the US
Authors: Malcomson James M. , Mavroeidis Sophocles
Published: July 2017

This paper uses robust econometric methods to assess previous empirical results for the Mortensen and Pissarides () matching model. Assuming all wages are negotiated each period is inconsistent with the history dependence in US wages, even allowing for heterogeneous match productivities, time to build vacancies and credible bargaining. Flexible wages for job changers, with rigid wages for job stayers, allows the model to capture this history dependence and is not inconsistent with parameter calibrations in the literature. Such wage rigidity affects only the timing of wage payments over the duration of matches; conclusions about other characteristics are unaffected by it.
Three relapses after a haploidentical transplantation in a pediatric patient: Cure with no further transplantation
Authors: Uygun Vedat , Daloglu Hayriye , Öztürkmen Seda , Karasu Gulsun , Yesilipek Akif
Published: July 2017

Isolated extramedullary relapse (EMR) after hematopoietic stem cell transplantation (HSCT) is a highly fatal condition that creates uncertainty regarding treatment options. Although certain approaches such as repeat HSCT and donor lymphocyte infusion are recommended, we report a patient with acute lymphoblastic leukemia who had three isolated EMRs after HSCT at different locations and at different times that were responsive to local and systemic therapies, without the need for a second transplantation.
Service delivery weaknesses within education and healthcare: Applying empirics from Kenya, Uganda, Tanzania, and Senegal
Authors: Hausken Kjell , Ncube Mthuli
Published: July 2017

Civil servants such as teachers and doctors allocate their resources into service delivery that benefits society, and alternative efforts for income. With low salary or high cost of service delivery, or high value of alternative efforts, the latter may be chosen extensively. This may mean leaving one's job. Some idealists may focus loyally and exclusively on service delivery despite the challenges. Choosing alternative efforts cannot be eradicated, but its role can be reduced if one is aware of the logic of which factors impact how actors allocate their resources between service delivery and alternative efforts. We have used data from the education and healthcare sectors in the African countries of Kenya, Uganda, Tanzania and Senegal to show the deficient and poor service delivery within education and healthcare services. In both sectors, education and healthcare, and for all four countries, teachers spend far less than the designated time teaching pupils, and clinicians spend very little time with patients, per day.