bluuebunny/crossref_metadata_2025 huggingface dataset:
Townes–Brocks syndrome
Authors: Vester Udo , Weber Stefanie
Published: November 2015

Townes–Brocks syndrome (TBS) is an autosomal dominant disease with variable expression. Classical features are imperforate anus, dysplastic ears with congenital hearing deficit, and triphalangeal thumbs in most cases. A variety of other malformations (renal, genitourinary, heart, central nervous system, eyes) or hypothyroidism has been described. Mutations in SALL1 have been identified in patients with TBS and genetic testing allows confirmation of the diagnosis. Familiar and sporadic forms (caused by de novo mutations) seem to be equally distributed. Renal involvement in TBS is not uncommon and includes renal agenesis, hypo-/dysplasia, and renal cysts and may eventually lead to chronic renal failure. As renal function may not deteriorate before adulthood, renal function should be monitored in all patients. As cases with TBS can be oligosymptomatic, TBS should be suspected in every case with unexplained renal failure, minor abnormalities, or indicative family history. Genetic counselling is mandatory in identified cases.
Renal coloboma syndrome
Authors: Vester Udo , Weber Stefanie
Published: November 2015

Renal coloboma syndrome is characterized by hypodysplasia of the kidneys and optic never anomalies. Dominant mutations in the paired box PAX2 gene have been defined as the underlying cause. Paired box proteins are important proteins involved in early organogenesis and PAX2 is highly expressed in the kidney, eye, and ear. This pattern of expression explains the spectrum of anomalies observed in RCS patients. The phenotypic variability of mutation carriers is high but ocular anomalies are detectable in almost all affected individuals. In some patients hearing impairment is observed. End-stage renal disease develops in the large majority of patients with PAX2 mutations and associated hypodysplasia of the kidneys.
The elderly patient
Authors: Birrell Fraser , O’Connell Janice
Published: November 2015

In this chapter, we describe how the process of ageing can itself affect the diagnosis and treatment of musculoskeletal conditions. We outline general principles concerning the clinical presentation of rheumatological diseases in older patients, as well as providing specific guidance on the diagnosis and management of the commoner conditions encountered in practice in the United Kingdom.
The eye
Authors: Petrushkin Harry , Stanford Miles
Published: November 2015

The ophthalmologist has a large part to play in the management of many rheumatological diseases. These diseases can cause a number of symptoms from mild ocular discomfort to sudden blindness. In addition, many rheumatological diseases have helpful ophthalmic signs, which can aid diagnosis.
This chapter has been written to help rheumatologists identify these signs and symptoms. We have started by summarizing the common pathology found in patients with rheumatological diseases (dry eye syndromes, conjunctivitis, episcleritis, scleritis, uveitis, and optic neuropathy). This has been arranged working backwards from the front of the eye towards the retina and optic nerve. The rheumatological conditions that give rise to ophthalmic signs (giant cell arteritis, systemic lupus erythematosus, polyarteritis nodosa, Wegner’s granulomatosis, systemic sclerosis, rheumatoid arthritis, seronegative arthropathies, sarcoidosis, and Behçet’s disease) have then been summarized, including a section of paediatric conditions (juvenile idiopathic arthritis, spondyloarthropathies, and multisystemic illness). Finally, treatment regimes and recent guidelines have been covered for the screening of uveitis in juvenile idiopathic arthritis and the management of patients taking hydroxychloroquine.
We hope that both rheumatologists in training and consultants find this chapter a useful clinical aid, and that it encourages them to look closely for subtle signs that will help improve the management of their patients.
Genetics of chronic musculoskeletal pain
Authors: Holliday Kate L. , Thomson Wendy , McBeth John , Nair Nisha
Published: November 2015

Chronic pain disorders are prevalent and a large burden on health care resources. Around 10% of the general population report chronic widespread pain, which is the defining feature of fibromyalgia. Fibromyalgia is a poorly understood idiopathic disorder which is also characterized by widespread tenderness and commonly occurs with comorbid mood disorders, fatigue, sleep disturbance, and cognitive dysfunction.
A role for genetics in chronic pain disorders has been identified by twin studies, with heritability estimates of around 50%. Susceptibility genes for chronic pain are likely to be involved in pain processing or the psychological component of these disorders. A number of genes have been implicated in influencing how pain is perceived due to mutations causing monogenic pain disorders or an insensitivity to pain from birth. The role of common variation, however, is less well known. The findings from human candidate gene studies of musculoskeletal pain to date are discussed. However, the scope of these studies has been relatively limited in comparison to other complex conditions.
Identifying susceptibility loci will help to determine the biological mechanisms involved and potentially new therapeutic targets; however, this is a challenging research area due to the subjective nature of pain and heterogeneity in the phenotype. Using more quantitative phenotypes such as experimental pain measures may prove to be a more fruitful strategy to identify susceptibility loci. Findings from these studies and other potential approaches are discussed.
Rituximab and abatacept
Authors: Isaacs John D. , Brown Philip M.
Published: November 2015

Two biologics that target cells have been licensed to treat rheumatoid arthritis (RA). Rituximab is a chimeric monoclonal antibody (mAb) against CD20 that depletes B cells; abatacept is a soluble form of CTLA-4 that blocks costimulation and interferes with T-cell function. Both drugs alleviate signs and symptoms of RA and have been shown to retard radiographic progression. Rituximab is licensed for use following failure of tumour necrosis factor (TNF) blockade whereas abatacept’s licence permits use as a first-line biologic. As with other biologics, the use of either drug is associated with an enhanced risk of serious infections; additionally, rituximab in particular can cause infusion reactions, requiring prophylaxis. By targeting cells that are central to RA pathogenesis, these drugs provide important additional therapeutic options for patients with RA.
Septic arthritis in adults
Authors: McGregor Laura , Gupta Monica N. , Field Max
Published: November 2015

Septic arthritis (SA) is a medical emergency with mortality of around 15%. Presentation is usually monoarticular but in more than 10% SA affects two or more joints. Symptoms include rapid-onset joint inflammation with systemic inflammatory responses but fever and leucocytosis may be absent at presentation. Treatment according to British Society of Rheumatology/British Orthopaedic Association (BSR/BOA) guidelines should be commenced if there is a suspicion of SA.
At-risk patients include those with primary joint disease, previous SA, recent intra-articular surgery, exogenous sources of infection (leg ulceration, respiratory and urinary tract), and immunosupression because of medical disorders, intravenous drug use or therapy including tumour necrosis factor (TNF) inhibitors.
Synovial fluid should be examined for organisms and crystals with repeat aspiration as required. Most SA results from haematogenous spread-sources of infection should be sought and blood and appropriate cultures taken prior to antibiotic treatment. Causative organisms include staphylococcus (including meticillin-resistant Staphylococcus aureus, MRSA), streptococcus, and Gram-negative organisms (in elderly patients), but no organism is identified in 43%, often after antibiotic use before diagnosis.
Antibiotics should be prescribed according to local protocols, but BSR/BOA guidelines suggest initial intravenous and subsequent oral therapy. Medical treatment may be as effective as surgical in uncomplicated native SA, and can be cost-effective, but orthopaedic advice should be sought if necessary and always in cases of infected joint prostheses.
In addition to high mortality, around 40% of survivors following SA develop limitation of joint function. Guidelines provide physicians with treatment advice aiming to limit mortality and morbidity and assist future research.
Parasitic infection
Authors: Ogunbambi Olabambo , Patel Yusuf I.
Published: November 2015

Parasitic infections remain prevalent, particularly in the developing world. However, increasing global travel poses a risk of contracting parasitic infections while travelling through endemic areas and therefore all medical practitioners should remain aware of parasitic infections and investigate for them when appropriate. Increased understanding of the relationship of parasites with the immune system has led to some progress with therapeutics but this still lags behind other infectious diseases. In this chapter we outline the musculoskeletal manifestations of parasitic infection and updated therapeutic approaches to these infections. The burden of disease may change with increasing use of potent biologic immunosuppressants and global travel, as seen in HIV-related immunosuppression, but as yet no significant increased incidence of parasitic infection has been reported within ’rheumatic diseases’ cohorts around the world.
Pathogenesis of osteoarthritis
Authors: Vincent Tonia L. , Troeberg Linda
Published: November 2015

Understanding pathogenic mechanism in disease is critical for development of targeted therapeutic strategies. Although there are, at this time, only a handful of experimental approaches for treating osteoarthritis (OA), until 10 years ago this disease was almost universally considered an unmodifiable condition. Emerging data during this time, largely fuelled by studies in rodent models, has completely changed the paradigm of disease pathogenesis and has for the first time, generated novel, realistic targets for this highly prevalent and disabling condition. These targets include the aggrecanases, members of the ADAMTS family, and collagenases, which together are critical for the early breakdown of the extracellular matrix of cartilage. Some recent success has also been demonstrated by targeting bone in disease. Development of pain in OA is complex and likely arises from different tissues at different stages of disease. In the following section we describe the pathological features of OA, and discuss the evolution of theories of OA pathogenesis and factors that have limited mechanistic clarity in this disease. We summarize the molecular pathways that are now known to be active in disease, and consider how these identified molecular pathways could be linked to known epidemiological risk factors. We finish by discussing possible future therapeutic strategies that will emerge from these discoveries and the current limitations in implementing new therapies in OA.
Disorders of bone mineralization—osteomalacia
Authors: Jadon Deepak R. , Ahmed Tehseen , Bhalla Ashok K.
Published: November 2015

Disorders of bone mineralization cause rickets in children and osteomalacia in adults. Both remain common in developing countries. Incidence in Western countries had declined since the fortification of foodstuffs, but appears to be increasing again. Calcium and inorganic phosphate are the key precursors for bone mineralization and growth. The commonest aetiology of osteomalacia is vitamin D deficiency, primarily due to low dietary intake and inadequate sun exposure. In the last decade gene mutations have been identified that are responsible for inherited rickets and osteomalacia, particularly those that result in phosphate deficiency, hypophosphatasia, and vitamin D receptor or metabolizing enzyme mutations. Additionally, the pathogenesis of tumour-induced osteomalacia is becoming better understood. Osteomalacia may present as bone pain and tenderness, muscle pain and weakness, and skeletal deformity or fracture. Key investigations include biochemical assessment and plain radiographs. Radioisotope bone scans and bone biopsy may be considered in selected cases. Differential diagnoses include osteoporosis, seronegative arthritides, and localized soft tissue disorders. Treatment, guided by the underlying aetiology, aims to reduce symptoms, fracture risk, bone deformity and sequelae. Vitamin D deficient patients require vitamin D and calcium replacement.
Childhood regional conditions
Authors: Houghton Kristin
Published: November 2015

Musculoskeletal (MSK) complaints are common in childhood. The majority of causes are benign and self-limiting, but MSK symptoms may be the presenting feature of serious life-threatening illness or chronic disease. Pain is often attributed to minor trauma, and atraumatic causes including infectious, inflammatory, and oncologic conditions, amplified musculoskeletal pain syndromes, and normal skeletal growth variants need to be considered. The age of the child helps identify the possible developmental conditions unique to the growing paediatric skeleton. Evaluation and management requires a thorough history and physical examination, and understanding of normal development.
This chapter reviews common MSK regional conditions in childhood.
Below the ankle angioplasty: treatment rationale and access techniques
Authors: Kitrou Panagiotis , Katsanos Konstantinos
Published: November 2015

A 70-year-old woman underwent an urgent endovascular below the knee therapeutic procedure in the interventional radiology department. The cause of admission was critical limb ischaemia with rest pain and extensive foot ulcer located mainly at the posterior aspect of the distal calf, the calcaneus, and the posteromedial aspect of the right foot (tissue loss, Rutherford stage 6). The patient also had a previous common femoral to popliteal artery bypass on the same leg. The ankle-brachial index was 0.6 on the right side. Following antegrade puncture, selective digital subtraction angiography showed a patent bypass graft with long total occlusions of the anterior tibial and posterior tibial arteries. The peroneal artery was the only patent tibial artery to the ankle. The area of tissue loss related to the angiosomal distribution of the posterior tibial artery, but was supplied by peroneal perforating collaterals below the ankle. The posterior tibial artery was treated with a combined antegrade and retrograde tibial approach (SAFARI technique) in order to re-establish a direct inline flow to the area of interest. An attempt to restore flow to foot via the anterior tibial artery was made, but it was unsuccessful. On the three-month surveillance follow-up with duplex ultrasound, the patient had a two-vessel run-off to the foot, the posterior tibial artery, and the peroneal artery without any significant stenosis. There was progressive healing of the tissue loss (Rutherford stage reduced from 6 to 5) and the ankle-brachial index had improved by 0.25 (from 0.6 up to 0.85).
Phlegmasia cerulea dolens: percutaneous treatment
Authors: Mezes Peter , Karunanithy Narayan
Published: November 2015

Phlegmasia cerulea dolens is a potentially limb-threatening complication of acute severe iliofemoral deep vein thrombosis. This case discusses the mode of presentation, the endovascular therapeutic options, and the technical aspects of carrying out these procedures, and presents a literature review of the supporting evidence.
General Protocol
Authors: Barton Brandon R. , Hall Deborah A.
Published: November 2015

Given the broad diversity of movement disorders, with a number of rare and unusual conditions, the nature of the movement disorder or the referral will not be clear on presentation. In addition, some patients will have complex disorders in which there are multiple types of movements present; in such cases, one cannot easily pick a specific movement disorders protocol and a general protocol is desired that has a high probability to capture the key elements of any disorder. The general movement disorders protocol captures the key elements that are needed for any reasonable video. Other examination findings that need highlighting may be added at the discretion of the examiner. This protocol forms the core of the other movement disorder videotaping protocols.
Atypical Parkinsonism
Authors: Barton Brandon R. , Hall Deborah A.
Published: November 2015

Not all patients with Parkinsonian motor features of bradykinesia, rigidity, tremor, or postural instability have Parkinson disease (PD). A large number of rare conditions may present with the initial features of PD, but then develop atypical signs such as early and prominent autonomic failure, extraocular movement abnormalities, dementia, contractures, spasticity, bulbar signs (severe dysphagia and dysarthria), and frequent falls. The number of atypical Parkinsonian disorders does not allow for a specific protocol for every disease, and in most disorders, the PD protocol will cover the general features common to all of these diseases. However, there are a few situations in which key features of atypical Parkinsonism can be integrated into the videotape with specific protocols, including examination of eye movements and praxis.
Ataxia
Authors: Barton Brandon R. , Hall Deborah A.
Published: November 2015

Ataxia describes uncoordinated movement and may be present in almost any area of the body. Typically it affects gait and balance most prominently, but it can also cause disability from clumsiness of limb movements and speech impairment. It can be highly variable and is usually secondary to cerebellar dysfunction. The ataxia protocol includes evaluation of speech, eye movements, movements of the extremities, and tandem gait, in addition to some measures assessing parkinsonism (which is often also present with adult neurodegenerative disorders). In addition, all components of the Scale for the Assessment and Rating of Ataxia (SARA) are illustrated in the video examples, including the finger chase.
In‐Depth Study of Durum Wheat Grain Tissue Distribution at Milling
Authors: Raggiri Vincent , Barron Cécile , Abecassis Joël , Lullien‐Pellerin Valérie
Published: November 2015

The starchy endosperm proportion in durum wheat grain and its ability to be isolated from the peripheral tissues appear as main intrinsic characteristics potentially related to the milling value but still difficult to assess. In this study, several durum wheat samples displaying distinct grading characteristics were analyzed and processed through a pilot mill. The histological composition of grains and milling fractions was monitored by using identified biochemical markers of each wheat grain tissue. Contrasted milling yields of semolina and flour were observed between samples, despite displaying a similar starchy endosperm proportion determined by hand dissection. These yields were related both to differences in the starchy endosperm extraction and to the presence of the aleurone layer, particularly its cellular content. Furthermore, two distinct types of fractionation behavior of the aleurone layer were distinguished depending on the wheat grain sample. Extraction of the envelopes and embryonic axis into semolina and flours were found negligible in comparison with the other tissues.
Severe Pediatric Thyroid Eye Disease: Surgical Case Series
Authors: Wu Chris Y. , Elner Victor M. , Kahana Alon
Published: October 2015

Thyroid eye disease (TED) usually has mild manifestations in pediatric patients, and orbital decompression is rarely necessarily. The authors present the clinical course of 3 pediatric patients age 16 or younger at the time of decompression surgery with severe orbitopathy. Case 1 is a 9-year-old prepubertal Asian-American female with Graves’ disease and TED who underwent balanced decompression for compressive optic neuropathy. Case 2 is a 14-year-old white female with Graves’ disease and TED who underwent balanced decompression for compressive optic neuropathy, stretch optic neuropathy, and globe subluxation. Case 3 is a 14-year-old African-American male with unilateral euthyroid TED who underwent staged right-sided lateral, medial, and floor decompressions for asymmetric proptosis. All cases also had disfiguring proptosis and exposure keratopathy, and in all cases, surgery successfully ameliorated the indications. Children, both pre- and post-pubertal, can rarely manifest visually threatening severe orbitopathy due to TED. This represents the first reports of thyroid-related optic neuropathy and globe subluxation in pediatric patients. Further studies examining the mechanism responsible for the disparities in pediatric and adult TED are warranted.
Emergency physician sex and emergency department resource use
Authors: Miró Òscar , Busca Pablo
Published: October 2015

Objective

We investigated whether there are differences in emergency department (ED) patient management associated with emergency physician (EP) sex, specifically in terms of ordering investigations and hospital admissions.

Methods

We included all EPs working as consultants for at least 24 consecutive months at a Spanish ED during an 8-year period. Every annual period was considered independently. The classificatory variable was EP sex. For every annual period we compiled age and years of experience of each EP, the number of patients who attended, and patient distribution in triage categories. To analyze ED resource use by each EP and period, we recorded percentages of blood tests, radiography, ultrasonography, computerized tomography (CT) scan, and hospital admission orders.

Results

Fifty EPs (27 women and 23 men) were included, 291 annual periods were analyzed (132 for women and 159 for men) and 256 524 patient attendances were recorded (114 086 by women and 142 438 by men). Blood tests were ordered in 57.2% of cases, radiography in 58.0%, ultrasounds in 5.0%, CT scans in 7.0%, and hospitalizations in 28.4%. Compared with men, women ordered 6.8% (95% confidence interval 6.1–7.5%) more blood tests, 4.6% (4.3–5.3%) more radiographies, 15.2% (11.6–18.9%) more ultrasonographies, 11.1% (8.1–14.1%) more CT scans, and 12.1% (10.8–13.4%) more hospitalizations. These differences maintained statistical significance in the stratified analysis by EP experience, and were observed for most of the years analyzed.

Conclusion

Female EPs order more investigations and admit more patients, although from our results the reason for this is unclear, and the impact on healthcare effectiveness and patient outcome is unknown.
Global Data Sharing in Alzheimer Disease Research
Authors: Ashish Naveen , Bhatt Priya , Toga Arthur W.
Published: October 2015

Many investigators recognize the importance of data sharing; however, they lack the capability to share data. Research efforts could be vastly expanded if Alzheimer disease data from around the world was linked by a global infrastructure that would enable scientists to access and utilize a secure network of data with thousands of study participants at risk for or already suffering from the disease. We discuss the benefits of data sharing, impediments today, and solutions to achieving this on a global scale. We introduce the Global Alzheimer’s Association Interactive Network (GAAIN), a novel approach to create a global network of Alzheimer disease data, researchers, analytical tools, and computational resources to better our understanding of this debilitating condition. GAAIN has addressed the key impediments to Alzheimer disease data sharing with its model and approach. It presents practical, promising, yet, data owner-sensitive data-sharing solutions.
Balanced Oscillatory Coupling Improves Information Flow
Authors: Peterson Erik J. , Voytek Bradley
Published: October 2015

All animals are able to rapidly change their behavior. The neural basis of such flexibility requires that groups of distant neural ensembles rapidly alter communications with selectivity and fidelity. Low frequency oscillations are a strong candidate for how neurons coordinate communication via the dynamic instantiation of functional networks. These dynamic networks are argued to rapidly guide the flow of information, with the presumption that stronger oscillations more strongly influence information flow. Surprisingly, there is scant evidence or theoretical support for how oscillatory activity might enhance information flow. Here we introduce a novel computational model for oscillatory neural communication and show that, rather than the strength of the oscillation, it is the balance between excitatory and inhibitory neuronal activity that has the largest effect on information flow. When coupling between an oscillation and spiking has balanced excitatory-inhibitory inputs, information flow is enhanced via improved discriminability between signal and noise. In contrast, when coupling is unbalanced, driven either by excessive excitation or inhibition, information flow is obstructed, regardless of the strength of the oscillation. A multitude of neuropathologies, including Parkinson’s disease, schizophrenia, and autism, are associated with oscillatory disruptions and excitation-inhibition imbalances. Our results show that understanding the distinction between balanced and unbalanced oscillatory coupling offers a unifying mechanistic framework for understanding effective neural communication and its disruption in neuropathology.
Distinguishing contemporary hybridization from past introgression with post-genomic ancestry-informative SNPs in strongly differentiatedCionaspecies
Authors: Bouchemousse Sarah , Liautard-Haag Cathy , Bierne Nicolas , Viard Frédérique
Published: October 2015

Biological introductions bring into contact species that can still hybridize. The evolutionary outcomes of such secondary contacts may be diverse (e.g. adaptive introgression from or into the introduced species) but are not yet well examined in the wild. The recent secondary contact between the non-native sea squirtCiona robusta(formerly known asC. intestinalistype A) and its native congenerC. intestinalis(formerly known asC. intestinalistype B), in the western English Channel, provides an excellent case study to examine. To examine contemporary hybridization between the two species, we developed a panel of 310 ancestry-informative SNPs from a population transcriptomic study. Hybridization rates were examined on 449 individuals sampled in 8 sites from the sympatric range and 5 sites from allopatric ranges. The results clearly showed an almost complete absence of contemporary hybridization between the two species in syntopic localities, with only one first generation hybrid and no other genotype compatible with recent backcrosses. Despite the almost lack of contemporary hybridization, shared polymorphisms were observed in sympatric and allopatric populations of both species. Furthermore, one allopatric population from SE Pacific exhibited a higher rate of shared polymorphisms compared to all otherC. robustapopulations. Altogether, these results indicate that the observed level of shared polymorphism is more probably the outcome of ancient gene flow spread afterwards at a worldwide scale. They also emphasise efficient reproductive barriers preventing hybridization between introduced and native species, which suggests hybridization should not impede too much the expansion and the establishment of the non-native species in its introduction range.
In Vivo Voltage-Sensitive Dye Imaging of Mammalian Cortex Using “Blue” Dyes
Authors: Baker Bradley , Gao Xin , Wolff Brian S. , Jin Lei , Cohen Lawrence B. , Bleau Chun X. , Wu J.-Y.
Published: November 2015

Optical recording of membrane potential allows simultaneous measurements to be taken from many different locations in the nervous system. This is important in studies of the nervous system in which simultaneous activity can occur at the regional, cellular, and subcellular levels. New “blue” dyes, developed by Amiram Grinvald’s group, are a great advance for in vivo voltage-sensitive dye imaging of mammalian cortex. The blue dyes are excited by red light (630 nm) that does not overlap with light absorption of hemoglobin (510–590 nm). This virtually eliminates the heart pulsation artifact.
Methods for Probing Lysosomal Membrane Permeabilization
Authors: Jäättelä Marja , Nylandsted Jesper
Published: November 2015

Cell death triggered by lysosomal membrane permeabilization (LMP) is gaining increased interest as target for cancer therapy, but the death pathway also plays an important role in normal physiology (e.g., during involution of the mammary gland). LMP-induced cell death is triggered by release of hydrolases including cysteine cathepsin proteases from the lysosomal lumen into the cytosol. Limited release of proteases to the cytoplasm induces apoptosis or apoptosis-like cell death, whereas massive LMP results in rapid cellular necrosis. Here we introduce three complementary methods for quantifying and visualizing LMP: (i) monitoring LMP by immunocytochemistry, (ii) visualizing LMP by fluorescent dextran release, and (iii) quantification of LMP by activity measurements of lysosomal enzymes in digitonin-extracted cytosol.
Optimization of the promotion mix in the healthcare industry
Authors: Haughton Dominique , Hua Guangying , Jin Danny , Lin John , Wei Qizhi , Zhang Changan
Published: November 2015

Purpose

– The purpose of this paper is to propose data mining techniques to model the return on investment from various types of promotional spending to market a drug and then use the model to draw conclusions on how the pharmaceutical industry might go about allocating promotion expenditures in a more efficient manner, potentially reducing costs to the consumer. The main contributions of the paper are two-fold. First, it demonstrates how to undertake a promotion mix optimization process in the pharmaceutical context and carry it through from the beginning to the end. Second, the paper proposes using directed acyclic graphs (DAGs) to help unravel the direct and indirect effects of various promotional media on sales volume.

Design/methodology/approach

– A synthetic data set was constructed to prototype proposed data mining techniques and two analyses approaches were investigated.

Findings

– The two methods were found to yield insights into the problem of the promotion mix in the context of the healthcare industry. First, a factor analysis followed by a regression analysis and an optimization algorithm applied to the resulting equation were used. Second, DAG was used to unravel direct and indirect effects of promotional expenditures on new prescriptions.

Research limitations/implications

– The data are synthetic and do not incorporate any time autocorrelations.

Practical implications

– The promotion mix optimization process is demonstrated from the beginning to the end, and the issue of negative coefficient in promotion mix models are addressed. In addition, a method is proposed to identify direct and indirect effects on new prescriptions.

Social implications

– A better allocation of promotional expenditures has the potential for reducing the cost of healthcare to consumers.

Originality/value

– The contributions of the paper are two-fold: for the first time in the literature (to the best of the authors’ knowledge), the authors have undertaken a promotion mix optimization process and have carried it through from the beginning to the end Second, the authors propose the use of DAGs to help unravel the effects of various promotion media on sales volume, notably direct and indirect effects.
Socially responsible investing: a review of the critical issues
Authors: Junkus Joan , Berry Thomas D.
Published: November 2015

Purpose

– The purpose of this paper is to provide a review of the most recent work in major finance journals on socially responsible investment (SRI). While SRI involves individual investors, firms, and investment managers, the authors concentrate primarily on the investment view.

Design/methodology/approach

– The authors briefly review the development of socially responsible investing (SRI) and the theoretical issues related to SRI and investment choice. This is followed by a review of the empirical results concerning firm value. The question of whether SR mutual funds and SR indexes differ in performance or other characteristics from their conventional counterparts is discussed next, and lastly the authors present suggestions for future research directions.

Findings

– Despite the large and extensive amount of empirical research published on SRI in recent years, the authors find no definitive answer to the question of SR actions for either the firm or the investor. For firms, evidence linking corporate social responsibility (CSR) rankings with higher value is mixed, and depends on the type of CSR behavior studied as well as the measures of firm performance used. The performance of SR mutual funds and indexes generally are not significantly different from conventional funds or indexes, but again these results are also highly dependent on model specification, time period, benchmark, and other characteristics of the study.

Practical implications

– The value of SR investing has not been definitely proved. This means, however, that there is room for further on this important topic.

Originality/value

– This paper synthesizes and presents the most recent research on SRI from a wide variety of refereed sources.
Resource specialists lead local insect community turnover associated with temperature – analysis of an 18‐year full‐seasonal record of moths and beetles
Authors: Thomsen Philip Francis , Jørgensen Peter Søgaard , Bruun Hans Henrik , Pedersen Jan , Riis‐Nielsen Torben , Jonko Krzysztof , Słowińska Iwona , Rahbek Carsten , Karsholt Ole
Published: November 2015

Insect responses to recent climate change are well documented, but the role of resource specialization in determining species vulnerability remains poorly understood. Uncovering local ecological effects of temperature change with high‐quality, standardized data provides an important first opportunity for predictions about responses of resource specialists, and long‐term time series are essential in revealing these responses.

Here, we investigate temperature‐related changes in local insect communities, using a sampling site with more than a quarter‐million records from two decades (1992–2009) of full‐season, quantitative light trapping of 1543 species of moths and beetles.

We investigated annual as well as long‐term changes in fauna composition, abundance and phenology in a climate‐related context using species temperature affinities and local temperature data. Finally, we explored these local changes in the context of dietary specialization.

Across both moths and beetles, temperature affinity of specialists increased through net gain of hot‐dwelling species and net loss of cold‐dwelling species. The climate‐related composition of generalists remained constant over time. We observed an increase in species richness of both groups. Furthermore, we observed divergent phenological responses between cold‐ and hot‐dwelling species, advancing and delaying their relative abundance, respectively. Phenological advances were particularly pronounced in cold‐adapted specialists.

Our results suggest an important role of resource specialization in explaining the compositional and phenological responses of insect communities to local temperature increases. We propose that resource specialists in particular are affected by local temperature increase, leading to the distinct temperature‐mediated turnover seen for this group. We suggest that the observed increase in species number could have been facilitated by dissimilar utilization of an expanded growing season by cold‐ and hot‐adapted species, as indicated by their oppositely directed phenological responses. An especially pronounced advancement of cold‐adapted specialists suggests that such phenological advances might help minimize further temperature‐induced loss of resource specialists.

Although limited to a single study site, our results suggest several local changes in the insect fauna in concordance with expected change of larger‐scale temperature increases.
Sinorhizobium fredii HH103 bacteroids are not terminally differentiated and show altered O‐antigen in nodules of the Inverted Repeat‐Lacking Clade legume Glycyrrhiza uralensis
Authors: Crespo‐Rivas Juan C. , Guefrachi Ibtissem , Mok Kenny C. , Villaécija‐Aguilar José A. , Acosta‐Jurado Sebastián , Pierre Olivier , Ruiz‐Sainz José E. , Taga Michiko E. , Mergaert Peter , Vinardell José M.
Published: November 2015

In rhizobial species that nodulate inverted repeat‐lacking clade (IRLC) legumes, such as the interaction between Sinorhizobium meliloti and Medicago, bacteroid differentiation is driven by an endoreduplication event that is induced by host nodule‐specific cysteine rich (NCR) antimicrobial peptides and requires the participation of the bacterial protein BacA. We have studied bacteroid differentiation of Sinorhizobium fredii HH103 in three host plants: Glycine max, Cajanus cajan and the IRLC legume Glycyrrhiza uralensis. Flow cytometry, microscopy analyses and viability studies of bacteroids as well as confocal microscopy studies carried out in nodules showed that S. fredii HH103 bacteroids, regardless of the host plant, had deoxyribonucleic acid (DNA) contents, cellular sizes and survival rates similar to those of free‐living bacteria. Contrary to S. meliloti, S. fredii HH103 showed little or no sensitivity to Medicago NCR247 and NCR335 peptides. Inactivation of S. fredii HH103 bacA neither affected symbiosis with Glycyrrhiza nor increased bacterial sensitivity to Medicago NCRs. Finally, HH103 bacteroids isolated from Glycyrrhiza, but not those isolated from Cajanus or Glycine, showed an altered lipopolysaccharide. Our studies indicate that, in contrast to the S. meliloti‐Medicago model symbiosis, bacteroids in the S. fredii HH103‐Glycyrrhiza symbiosis do not undergo NCR‐induced and bacA‐dependent terminal differentiation.
Transcriptomic response during phage infection of a marine cyanobacterium under phosphorus‐limited conditions
Authors: Lin Xingqin , Ding Huiming , Zeng Qinglu
Published: November 2015

The transcriptomic responses of bacteria to environmental stresses have been studied extensively, yet we know little about how the stressed cells respond to bacteriophage infection. Here, we conducted the first whole transcriptome sequencing (RNA‐seq) study of stressed bacteria to phage infection by infecting the marine picocyanobacterium Prochlorococcus NATL2A with cyanomyovirus P‐SSM2 under P limitation, a strong selective force in the oceans. Transcripts of the P‐acquisition genes in the uninfected cells were enriched after P limitation, including the high‐affinity phosphate‐binding protein gene pstS. They were still enriched in the infected cells under P‐limited conditions. In contrast, transcripts of adenosine triphosphate (ATP) synthase and ribosomal protein genes were depleted in the uninfected cells after P limitation but were enriched during phage infection of P‐starved cells. Cyanophage P‐SSM2 contains pstS, and pstS and its adjacent gene g247 of unknown function were the only phage genes that were enriched under P‐limited conditions. We further found that the host pstS transcript number per cell decreased after infection, however, it was still much higher in the P‐limited infected cells than that in the nutrient‐replete cells. Moreover, phage pstS transcript number per cell was ∼20 times higher than the host copy, which may help maintain the host phosphate uptake rate during infection.
Śāntideva's Bodhicaryāvatāra in Translation: A Century of Interpretation of a Sanskrit Mahāyāna Text
Authors: Nelson Barbara
Published: November 2015

Many translations of Śāntideva's Bodhicaryāvatāra, a Sanskrit Mahāyāna Buddhist text of seventh/eighth‐century India, have been published since 1892. Śāntideva's Bodhicaryāvatāra is one of the few Indian Mahāyāna Buddhist texts available in Sanskrit and it was influential in Tibetan Buddhist schools. This article explores how translation of the Bodhicaryāvatāra is no longer the preserve of scholars but has moved to being carried out by Buddhist practitioners influenced by Tibetan schools of Buddhism. It shows how translators’ motives for translating the text have reflected changing attitudes to Buddhism and its texts. Śāntideva's Bodhicaryāvatāra has been translated as a source of information, a literary work, an inspirational work and, with the rise of Western interest in Tibetan Buddhism in the late twentieth century, as a vehicle for the transmission of Buddhist teachings. Nevertheless, further scholarly investigation of the Sanskrit text of the Bodhicaryāvatāra remains to be done.
Do Laws Influence the Cost of Real Estate Brokerage Services? A State Fixed Effects Approach
Authors: Nanda Anupam , Clapp John M. , Pancak Katherine A.
Published: November 2015

A FTC‐DOJ study argues that state laws and regulations may inhibit the unbundling of real estate brokerage services in response to new technology. Our data show that 18 states have changed laws in ways that promote unbundling since 2000. We model brokerage costs as measured by number of agents in a state‐level annual panel vector autoregressive framework, a novel way of analyzing wasteful competition. Our findings support a positive relationship between brokerage costs and lagged house price and transactions. We find that change in full‐service brokers responds negatively (by well over two percentage points per year) to legal changes facilitating unbundling.
The Interaction Between Lipoxygenase‐Catalyzed Oxidation and Autoxidation in Dry‐Cured Bacon and a Model System
Authors: Zhang Yingyang , Tang Jing , Zhao Jianying , Wu Haizhou , Ditta Yasir Allah , Zhang Jianhao
Published: November 2015

A model system was conducted to characterize the interaction between lipid autoxidation and enzyme‐catalyzed oxidation in dry‐cured bacon. This involved the use of a hydroxyl radical (HO•) generating system and the extraction and purification of lipoxygenases (LOX) from pork belly. The results showed that LOX activity rapidly (P < 0.05) increased during the curing of dry‐cured bacon. This may be because of the hydroxyl‐radical‐mediated oxidation from LOX‐Fe2+ to LOX‐Fe3+, which activates LOX. In addition, experiments of the model system also showed that LOX activity could be inhibited by increasing the substrate concentration, although substrate type and concentration had no effect on autoxidation. Moreover, LOX enzyme‐catalyzed oxidation and autoxidation could act synergistically to promote lipid oxidation irrespective of the substrate (linoleic or arachidonic acid). These results provide useful information for regulating lipid oxidation during the production of dry‐cured pork products.
Clinical Significance of Upsloping ST Depression on Resting Electrocardiogram
Authors: Khalid Umair , Birnbaum Yochai
Published: November 2015

Introduction

Upsloping ST depression is generally not associated with myocardial ischemia, yet there have been published reports that suggest otherwise.

Case History

A 34‐year‐old pregnant female presented with chest pain and palpitations. She was found to have supraventricular tachycardia, which resolved with intravenous adenosine. Few minutes later her ECG showed upsloping ST depression in leads V4–V6 that persisted for 1 hour after the resolution of the tachycardia. The patient was discharged in stable condition with outpatient follow‐up.

Conclusion

Upsloping ST depression in resting electrocardiogram may indicate cardiac ischemia in the presence of active cardiac symptoms. In the absence of ongoing symptoms however, it may be secondary to conditions other than ischemia.
Methods for Improving the Diagnosis of a Brugada ECG Pattern
Authors: Gottschalk Byron H. , Garcia‐Niebla Javier , Anselm Daniel D. , Glover Benedict , Baranchuk Adrian
Published: November 2015

Brugada syndrome (BrS) is an inherited channelopathy that predisposes individuals to malignant arrhythmias and can lead to sudden cardiac death. The condition is characterized by two electrocardiography (ECG) patterns: the type‐1 or “coved” ECG and the type‐2 or “saddleback” ECG. Although the type‐1 Brugada ECG pattern is diagnostic for the condition, the type‐2 Brugada ECG pattern requires differential diagnosis from conditions that produce a similar morphology. In this article, we present a case that is suspicious but not diagnostic for BrS and discuss the application of ECG methodologies for increasing or decreasing suspicion for a diagnosis of BrS.
Needle size in intravitreal injections – pain evaluation of a randomized clinical trial
Authors: Haas Paulina , Falkner‐Radler Christiane , Wimpissinger Barbara , Malina Magdalena , Binder Susanne
Published: November 2015

Purpose

To evaluate the influence of the needle size used for intravitreal (IVT) injections on patients' pain experience in a randomized, double‐armed, single‐blinded, clinical trial.

Methods

Patients included were randomized to have an IVT injection performed with a 27‐gauge needle (group 1) or with a 30‐gauge needle (group 2). The topical anaesthesia before the injection was standardized. Immediately after the injection, patients were asked to grade their pain using the visual analogue scale (VAS) and the Wong–Baker FACES scale. The main outcome measure was the pain score assessment. Cofactors analysed were patients' demographics (age and gender) and clinical characteristics (such as the number of previous IVT injections). In addition, scaled surgeon's questionnaires to assess the IVT injection procedure were evaluated. For statistical analysis, a regression model was used.

Results

The data of 208 patients (group 1: 104 patients; group 2: 104 patients) were analysed. There was no significant difference in the VAS pain scores (p > 0.18) and in the Wong–Baker pain scores (p > 0.59) between both treatment groups. Gender (p = 0.0288) and the number of previous IVT injections (p = 0.0028) significantly influenced the VAS pain scores (p < 0.05). Female patients and patients with a history of previous IVT injections had higher pain scores. The surgeon's questionnaire showed an overall preference towards the use of a 30‐gauge needle for IVT injections.

Conclusion

The use of a 30‐gauge needle for IVT injections showed no significant effect in pain relief compared to the use of a 27‐gauge needle. However, a 30‐gauge needle was preferred by all surgeons.
Country‐based reference values and international comparisons of clitoral size in healthy Nigerian newborn infants
Authors: Jarrett Olumide Olatokunbo , Ayoola Omolola Ouwakemi , Jonsson Björn , Albertsson‐Wikland Kerstin , Ritzen Martin
Published: November 2015

Aim

Clitoral size references are useful for diagnosing genital abnormalities. Despite the fact that examining the genitalia is an important aspect of newborn evaluation, few studies have been carried out to determine normal clitoral size in newborn infants. The aim of this study was to establish reference values for clitoral size in Nigerian newborn girls and to compare them with references from other ethnic populations.

Methods

A total of 244 healthy newborn girls delivered at 28–43 weeks gestation were enrolled in the study, and clitoral lengths and widths were measured at <72 hours.

Results

The mean clitoral length was 7.7 mm with a standard deviation of ±1.37 mm, while the mean clitoral width was 4.40 ± 0.89 mm. The clitoral length was significantly longer than those reported for Caucasian (4.00 ± 1.24 mm), Korean (3.82 ± 1.47), Turkish (4.93 ± 1.61) and Japanese (4.30 ± 1.10) babies.

Conclusion

The present results make it possible to evaluate clitoral size in Nigerian newborn baby girls in an objective way, to identify genital abnormalities and endocrine disorders. Based on this study, a clitoral length of more than 10 mm would be considered clitoromegaly in a newborn girl in Nigeria.