bluuebunny/crossref_metadata_2025 huggingface dataset:
Antidepressants and the risk of suicide in young persons – prescription trends and toxicological analyses
Authors: Isacsson G. , Ahlner J.
Published: June 2013

Objective

To assess trends in the use of antidepressants among young suicides after the warning that these drugs might increase the risk of suicide.

Method

Individual data of all 845 suicides in the 10‐ to 19‐year age group in Sweden in the time period 1992–2003 (baseline), and in 2004–2010 (after the warning). Outcome data are prescriptions of antidepressants prior to death and detections of antidepressants in post‐mortem toxicology.

Results

After the warning, suicide in this age group increased for five consecutive years (60.5%). The increase occurred among individuals not treated with antidepressants.

Conclusion

This study provides further support for the hypothesis that the warning, contrary to its intention, may have increased young suicides by leaving a number of suicidal young persons without treatment with antidepressants.
Pain is associated with heroin use over time in HIV‐infected Russian drinkers
Authors: Tsui Judith I. , Cheng Debbie M. , Coleman Sharon M. , Blokhina Elena , Bridden Carly , Krupitsky Evgeny , Samet Jeffrey H.
Published: June 2013

Aims

To evaluate whether pain was associated with increased risk of using heroin, stimulants or cannabis among HIV‐infected drinkers in Russia.

Design

Secondary analysis of longitudinal data from the HERMITAGE study (HIV's Evolution in Russia—Mitigating Infection Transmission and Alcoholism in a Growing Epidemic), a behavioral randomized controlled trial, with data collected at baseline, 6‐month and 12‐month visits.

Setting

Recruitment occurred at HIV and addiction treatment sites in St Petersburg, Russian Federation.

Participants

Six hundred and ninety‐nine HIV‐infected adult drinkers.

Measurements

The primary outcome was past month illicit drug use; secondary outcomes examined each drug (heroin, stimulants and cannabis) separately. The main predictor was pain that interfered at least moderately with daily living. General estimating equations (GEE) logistic regression models were used to evaluate the association between pain and subsequent illicit drug use, adjusting for potential confounders.

Findings

Participants reporting pain appeared to have higher odds of using illicit drugs, although the results did not reach statistical significance [adjusted odds ratio (OR) = 1.32; 95% confidence interval (CI) = 0.99, 1.76, P = 0.06]. There was a significant association between pain and heroin use (OR = 1.54; 95% CI = 1.11–2.15, P = 0.01) but not use of other drugs (OR = 0.75; 95% CI = 0.40–1.40, P = 0.35 for stimulants and OR = 0.70; 95% CI = 0.45–1.07, P = 0.09 for cannabis).

Conclusions

HIV‐infected Russian drinkers who report pain are more likely to use heroin over time than HIV‐infected Russian drinkers who do not report pain. Pain may be an unrecognized risk factor for persistent heroin use with implications for HIV transmission in Russia.
Movement outcomes of infants born moderate and late preterm
Authors: Odd David Edward , Lingam Raghu , Emond Alan , Whitelaw Andrew
Published: June 2013

Aim

To investigate whether children born between 32 and 36 weeks of gestation have an increased risk of motor coordination difficulties or cerebral palsy (CP) at age 7 years.

Methods

A cohort study based on the Avon Longitudinal Study of Parents and Children (ALSPAC). The primary outcomes were poor motor coordination, defined as an ALSPAC coordination test score <5th centile or the presence of CP. Exposure groups were defined as moderate or late preterm (32–36 weeks of gestation) or term (37–42 weeks). Regression models were used to investigate the association between gestational age and outcomes. Multiple imputation was used to account for missing covariate data.

Results

In the fully adjusted model, there was strong evidence that children born at moderate or late preterm had worse coordination (OR 1.41 (1.14–1.74)) and higher risk of CP (OR 6.38 (2.28–17.76)) than term peers. However, restricting the analysis to well‐grown infants born vaginally, in good condition, the associations attenuated substantially.

Conclusions

Moderate or late preterm infants were at increased risk of developing coordination problems and cerebral palsy. After restricting the analysis to ‘well’ infants the associations of gestation with the coordination measures and CP reduced substantially, suggesting that antenatal, intrapartum and neonatal causal pathways are likely to be involved.
Delivering perinatal psychiatric services in the neonatal intensive care unit
Authors: Hatters Friedman Susan , Kessler Ann , Nagle Yang Sarah , Parsons Sarah , Friedman Harriet , Martin Richard J.
Published: June 2013

Aim

To describe characteristics of mothers who would likely benefit from on‐site short‐term psychiatric services while their infant is in the neonatal intensive care unit (NICU).

Methods

For 150 consecutive mothers who were referred for psychiatric evaluation and psychotherapeutic intervention in an innovative NICU mental health programme, baseline information was collected. Data regarding their referrals, diagnosis, treatments and infants were analysed.

Results

Most mothers were referred because of depression (43%), anxiety (44%) and/or difficulty coping with their infant's medical problems and hospitalization (60%). Mothers of VLBW infants were disproportionately more likely to be referred. A majority of mothers accepted the referral and were treated; most only required short‐term psychotherapy. A minority resisted or refused psychiatric assessment; a quarter of these had more difficult interactions with staff or inappropriate behaviours. In these cases, the role of the psychiatrist was to work with staff to promote healthy interactions and to foster maternal‐infant bonding.

Conclusion

Overall, on‐site psychiatric services have been accepted by a majority of referred NICU mothers, and most did not require long‐term treatment. A considerable need exists for psychiatric services in the NICU to promote optimal parenting and interactions.
Urinary angiotensinogen as a novel marker of obstructive nephropathy in children
Authors: Taranta‐Janusz Katarzyna , Wasilewska Anna , Dębek Wojciech , Fiłonowicz Renata , Michaluk‐Skutnik Joanna
Published: June 2013

Aim

Obstructive nephropathy due to congenital or acquired urinary tract obstruction is one of the most important causes of chronic renal failure in children. There is a need for identification of new noninvasive urinary biomarkers to provide the clinician with fast, specific and reliable diagnostic and prognostic tool.

The aim of the study was to determine whether urinary angiotensinogen (uAGT) may be a useful marker of obstruction in children with hydronephrosis (HN) caused by ureteropelvic junction obstruction (UPJO).

Methods

The study cohort consisted of surgical group (SG): 31 children with severe HN who required surgery; nonsurgical group (NSG): 20 patients with mild HN, and reference group (RG): 19 healthy children. Urinary concentrations of angiotensinogen were measured using immunoenzymatic ELISA commercial kit and were expressed in ng/mg Cre (uAGT/uCre).

Results

uAGT/uCre level was higher in SG when compared to NSG (p < 0.01) and healthy participants (SG vs. RG: p < 0.01). The difference between the uAGT/uCre in NSG and RG was not statistically significant (p > 0.05). uAGT/uCre was correlated negatively with differential renal function (r = −0.46; p < 0.01).

Conclusion

The present pilot study has clearly demonstrated that children with UPJO showed increased uAGT levels, which correlated negatively with differential renal function in radionuclide scan.
An archaeometric contribution to the characterization of Renaissance maiolica from Urbino and a comparison with coeval maiolica from Pesaro (the Marches, central Italy)
Authors: Antonelli F. , Ermeti A. L. , Lazzarini L. , Verità M. , Raffaelli G.
Published: June 2013

The results of an archaeometric trial study performed on an important finding of Renaissance maiolica (mid‐15th to early 16th century) from the Ducal Palace of Urbino are presented. Mineralogical–petrographic data (XRD, OP, SEM–EDS) and chemical characterization (ICP/AES–MS: major and trace elements) of both ceramic bodies and glazes were compared with similar data provided on coeval maiolica found in archaeological excavations in Pesaro, now stored in the city's Municipal Museum, in order to verify an origin of the potteries from common (Pesaro) or different (Pesaro and Urbino) production centres. The results indicate that ceramic bodies were produced with quite similar illitic–calcareous clays, most probably taken from the same local Pliocene Formation. Similarities were also found concerning the glaze's glass (silica–lead), colourants (cobalt, copper and manganese) and pigments (lead antimonate and cassiterite).
Hereditary‐like urothelial carcinomas of the upper urinary tract benefit more from adjuvant cisplatin‐based chemotherapy after radical nephroureterectomy than do sporadic tumours
Authors: Hollande Clémence , Colin Pierre , de La Motte Rouge Thibault , Audenet François , Yates David R. , Phé Véronique , Ouzzane Adil , Droupy Stéphane , Ruffion Alain , de La Taille Alexandre , Guy Laurent , Cussenot Olivier , Rozet François , Xylinas Evanguelos , Zerbib Marc , Spano Jean‐Philippe , Khayat David , Bitker Marc‐Olivier , Rouprêt Morgan ,   French Collaborative National Working‐Group on UTUC
Published: June 2013

Objective

To evaluate the impact of ‘hereditary‐like’ status in upper tract urothelial carcinoma (UTUC) on the survival of patients who have undergone radical nephroureterectomy (RNU) and adjuvant chemotherapy.

Patients and Methods

A multicentre retrospective study was performed on all patients with high‐risk UTUC who underwent RNU and adjuvant cisplatin‐based chemotherapy.

Using a patient risk identification tool, we distinguished tumours suspected to be hereditary from sporadic tumours and compared survival rates.

Results

A total of 112 patients with a median age of 67 years were included. Hereditary‐like tumour status was detected in 35 patients (31.3%), while 77 patients (68.7%) had sporadic tumours.

The median age was significantly younger in the hereditary‐like tumour group (56.0 vs 69.8 years, P < 0.001). Overall survival (OS) after chemotherapy was significantly better in the group with hereditary‐like tumours than in the group with sporadic tumours (5‐year OS: 48.2 vs 32%; P = 0.008).

The cancer‐specific survival (CSS) rate was significantly better in the group with ‘hereditary‐like’ tumours than in the group with sporadic tumours (5‐year CSS: 58 vs 35%; P = 0.006).

Although there was a trend in favour of the hereditary‐like tumours, we observed no significant difference regarding progression‐free survival (PFS) between the two groups (5‐year PFS: 71 vs 52%; P = 0.07).

Conclusion

Adjuvant chemotherapy after RNU improves survival outcomes in patients with hereditary‐like UTUC compared with those with sporadic tumours.
Clinical trial risk in castration‐resistant prostate cancer: immunotherapies show promise
Authors: Tenuta Alessandro , Klotz Laurence , Parker Jayson L.
Published: June 2013

Objectives

To determine the risk of failure during drug development in castration‐resistant prostate cancer (CRPC) and to identify factors that could improve outcomes.

Methods

We investigated CRPC by analysing compounds in phase I to phase III clinical trials between 1998 and April 2011.

Drug development failures were classified as medical or commercial and were compared with industry expectations.

Compounds were excluded from analysis if their phase I occurred before 1998, if they targeted patients that were did not have hormone‐refractory prostate cancer, or if they did not assess outcomes such as overall survival, time to disease progression, or prostate‐specific antigen levels.

Results

Thorough searches of clinicaltrial.gov and other databases yielded 77 compounds that met the inclusion criteria.

The cumulative pass rate for first‐line compounds in CRPC was 3% and was far below aggregate industry expectations.

In total, there were nearly equivalent numbers of commercial and medical failures.

Biological products were found to have had greater relative success than small‐molecule drugs and biotechnology firms had been slightly more successful than pharmaceutical firms in this disease indication.

Phase III failures were high, despite equally high failures during phase II.

Conclusions

Currently, one in 33 compounds that enters clinical testing will be awarded US Food and Drug Administration approval. This appears to be the highest risk indication investigated to date, based on clinical trial studies alone, with an average cost of $1.411bn to bring a new drug to market when adjusted for risk.

Development of radical therapeutics such as immunotherapies may also be warranted instead of classic antineoplastic therapeutics.

Given the high clinical trial risk, efforts may have to shift to biomarker and surrogate endpoints to manage future clinical trial risk in prostate cancer.
Pretreatment staging of colon cancer in the Swedish population
Authors: Sjövall A. , Blomqvist L. , Martling A.
Published: June 2013

Aim

Preoperative staging of colon cancer according to Swedish national guidelines implies imaging evaluation of the primary tumour, liver and lungs. Failure to adhere to these guidelines results in negative scorings in the national registration system. In the present study we report the extent of compliance with these guidelines.

Method

Since 2007 clinical data on all patients diagnosed with colon cancer in Sweden have been collected in a national database. This includes information on pretherapeutic diagnostic imaging performed, pretherapeutic TNM stage and data on treatment and follow‐up. All patients diagnosed with colon cancer in Sweden between 2007 and 2010 were included.

Results

Nine thousand and eight‐three patients (i.e. 60.5% of all patients) had a complete pretherapeutic radiological evaluation; 65.2% had a CT or MRI of the primary tumour, whereas over 80% had examinations of the liver and lungs. There were no difference related to sex, but more patients under 75 years had a complete evaluation. There were large differences between different regions; one region performed a complete evaluation of 78.3% of all patients. The proportion of patients examined increased from 53.9 to 65.0% during the study period. Elective cases were more frequently evaluated before treatment than those with an emergency presentation.

Conclusion

Most patients in Sweden had a complete pretreatment imaging evaluation of the colon cancer with geographical and time‐dependent variations. Knowledge of the importance of these variations and correlation of pre‐ and postoperative TNM stage is warranted, and such studies are ongoing.
The influence of copper(II) ions on wool photostability in the dry state
Authors: Zhang Hu , Deb‐Choudhury Santanu , Plowman Jeffrey , Millington Keith , Dyer Jolon
Published: June 2013

It has been hypothesised that the presence of trace metals in wool, notably copper and iron, has an influence on the formation of free radicals under irradiation and thereby affects the photostability of wool and wool products, particularly in the wet state. There has been limited research evaluating the influence of copper ions on wool photodiscoloration. This study examined the relative photodiscoloration of wool bound with varied amounts of copper(II) ions under UVA, UVB and blue light irradiation in the dry state. Total reflectance and visible/near‐infrared absorbance spectra, tryptophan‐type fluorescence (λex = 295 nm, λem = 340 nm) and photoinduced chemiluminescence emissions of natural wool and copper(II)‐treated wool were characterised and contrasted. CIELAB colour space, D1925 yellowness and CIE whiteness values measured from irradiated wool samples indicate that wool treated with copper(II) solution at a higher concentration yellowed faster and experienced greater overall colour changes under UVA and UVB irradiation, whereas copper(II)‐treated wool seemed to be more photostable than untreated natural wool under blue light irradiation. It was also observed that binding copper ions to wool resulted in decreased tryptophan‐type fluorescence and photoinduced chemiluminescence emissions relative to untreated natural wool.
Evolution of a physiological trade‐off in a parasitoid wasp: how best to manage lipid reserves in a warming environment
Authors: Denis Damien , van Baaren Joan , Pierre Jean‐Sébastien , Wajnberg Eric
Published: June 2013

Ectothermic animals, especially insects, are probably the ones most affected, for better or worse, by variable thermic environment, for example in the case of global warming, as their metabolic rate is controlled by the ambient temperature. Parasitoid insects, at the third trophic level, are widely distributed worldwide, and they influence the population dynamics of their highly diverse insect hosts. An important feature of parasitoid wasps is their supposedly limited or non‐existent capacity to synthesize lipids during adulthood. As lipid level can be expected to determine whether they engage in maintenance or reproduction, parasitoid wasps are useful biological models for investigating how evolutionary trade‐offs in energy allocation to maintenance or reproduction are likely to alter in response to global climate change. To address this, we developed a state‐dependent stochastic dynamic programming model, which we parameterized using empirically derived data. The model shed light on the adaptive response of parasitoids with regard to three traits: activity rate, initial egg load, and egg production over the adult female's life span. We show that in a warmer climate, parasitoids devote smaller amounts of lipids to their reproductive effort and favour maintenance over reproduction. However, the bias towards maintenance is reduced when the parasitoids are able to adapt their activity rate to the features of their environment. This model could be tailored to a wide range of organisms with limited energy intake during their adult life.
Young people's views of UK mental health services
Authors: Plaistow James , Masson Kim , Koch Damaris , Wilson Jon , Stark Rosemary M. , Jones Peter B. , Lennox Belinda R.
Published: June 2013

Aims and method

Adolescence is the period of highest risk for the development of mental illness, but also the age group least likely to seek help from mental health services. We undertook a systematic review of the published literature on the views of young people of mental health services in the UK and a thematic analysis of the findings to explore the reasons behind this to guide those developing services for young people.

Results

Thirty‐one studies were identified, which captured the views of 13 605 young people including 625 young people who had experience of mental health services. Positive views to emerge were of qualities of mental health workers and encouraging self‐reliance. Negative views were of stigma, lack of information, medicalization of their problems and a lack of continuity of care.

Conclusions

Young people have consistent views of the positive and negative aspects of mental health services, which could be helpfully incorporated in the design of services. The views of some groups of young people have not been well represented, however, and the views of minority ethnic groups and those who have disengaged from services in particular need to be actively sought.
Audit of discharges from a regional service in the United Kingdom
Authors: Phillipson Adrian , Akroyd Mike , Carley Joanne
Published: June 2013

Aim

As early intervention in psychosis (EI) continues to develop, clinical governance maintains an important role in the ‘real world’ analysis of services. This paper details an audit of all discharges from a regional early intervention service in the United Kingdom, providing benchmarking information on service structure, interventions and outcomes. The background places the service in the context of national and international guidelines.

Methods

All discharges between service inception in 2004 and February 2011 were retrospectively examined and audited according to identified standards, based upon international and national guidelines. A total of 110 patients were discharged from the EI service after a period of involvement of at least 6 months.

Results

A high proportion of service users (55%) had their care transferred back to primary care after discharge. Physical health and social needs were well addressed, and almost half of individuals were in education, training or employment upon discharge. Most service users (69%) did not require inpatient admission during their involvement with the service. Although the majority had psychological, pharmacological and physical health needs addressed, there remained room for improvement when measured against identified standards.

Conclusions

This paper details outcomes of every patient seen by an EI service since inception, providing valuable benchmarking information for those involved in management of similar services, service redevelopment, commissioning, and implementation of evidence‐based practice. The proportion of service users in education, training or employment after discharge exceeded expectations considerably.
Psychopathology and affect dysregulation across the continuum of psychosis: a multiple comparison group study
Authors: Taylor Hannah E. , Stewart Suzanne L.K. , Dunn Graham , Parker Sophie , Bentall Richard P. , Birchwood Max , Morrison Anthony P.
Published: June 2013

Aim

There is evidence that psychotic‐like phenomena can be detected within the general population and that psychotic experiences lie on a continuum that also spans affective states. We aimed to investigate comparisons of a first‐episode psychosis group, an ‘at‐risk mental state group’ and a help‐seeking control group with non‐patients to explore whether affective states lie on a continuum of psychosis.

Method

Measures of psychotic‐like experiences, social anxiety and depression were administered to 20 patients experiencing first‐episode psychosis (FEP), 113 patients experiencing an ‘at‐risk’ mental state (ARMS), 28 patients who were help‐seeking but not experiencing a FEP or ARMS (HSC) and 30 non‐clinical participants (NC).

Results

For distress in relation to psychotic‐like experiences, the FEP, ARMS and HSC groups scored significantly higher than the NC group for the perceptual abnormalities and non‐bizarre ideas. In terms of severity of psychotic experiences, the FEP scored the highest, followed by the ARMS group, followed by the HSC and NC groups. The clinical groups scored significantly higher for depression than the non‐clinical group. Interestingly, only the FEP and the ARMS groups scored significantly higher than non‐patients for social anxiety.

Conclusions

These findings suggest that a psychosis continuum exists; however, this does not suggest that both psychosis and affective symptoms lie on the same continuum, rather it would appear the presence of such affective states that may affect help‐seeking behaviour and clinical status. The implications of these findings for clinical practice are discussed.
Cerebrovascular contributions to Alzheimer's disease pathophysiology and potential therapeutic interventions in mouse models
Authors: Thomason Lynsie A. M. , Stefanovic Bojana , McLaurin JoAnne
Published: June 2013

The inter‐relationship between vascular dysfunction and Alzheimer's disease pathology is not clearly understood; however, it is clear that the accumulation of amyloid‐beta peptide and loss of vascular function contribute to the cognitive decline detected in patients. At present, imaging modalities can monitor the downstream effects of vascular dysfunction such as cerebral blood flow alterations, white and gray matter lacunes, and ischemic lesions; however, they cannot distinguish parenchymal plaques from cerebrovascular amyloid. Much of our understanding regarding the relationship between amyloid and vascular dysfunction has come from longitudinal population studies and mouse models. In this review, we will discuss the breadth of data generated on vascular function in mouse models of Alzheimer's disease and cerebrovascular amyloid angiopathy. We will also discuss therapeutic strategies targeting the reduction of cerebrovascular amyloid angiopathy and improvement of vascular function.
Serine racemase as a prime target for age‐related memory deficits
Authors: Billard J.‐M.
Published: June 2013

The learning and memory deficits associated with non‐pathological ageing mainly result from alterations to the plasticity of neuronal network dynamics within the hippocampus. In addition to the broad spectrum of changes that affect the morphology and function of hippocampal excitatory circuits in the ageing brain, the impaired activation of theN‐methyl‐d‐aspartate subtype of glutamate receptors (NMDA‐R) is a typical feature, altering the induction and maintenance of long‐term potentiation, a major form of synaptic plasticity. In addition to glutamate, the binding of a co‐agonist at the strychnine‐insensitive glycine‐binding site is required forNMDA‐Ractivation. This review presents recent evidence that: (i) the amino acidd‐serine is an endogenous co‐agonist of synapticNMDA‐R and necessary for long‐term potentiation expression, (ii) reducedd‐serine levels in the hippocampus contribute to synaptic plasticity and memory deficits in normal ageing, and (iii) age‐related oxidative stress selectively targets hippocampal serine racemase to impactd‐serine availability in neuronal networks. These results emphasize the critical role of the hippocampald‐serine‐dependent pathway in changes affecting neuronal network dynamics in physiological ageing that underlie memory deficits. In addition, the central role of serine racemase in these changes opens new perspectives in the search for relevant therapeutic strategies aimed at reducing age‐related memory defects.
Amyloid‐β protein (Aβ) Glu11 is the major β‐secretase site of β‐site amyloid‐β precursor protein‐cleaving enzyme 1(BACE1), and shifting the cleavage site to Aβ Asp1 contributes to Alzheimer pathogenesis
Authors: Deng Yu , Wang Zhe , Wang Ruitao , Zhang Xiaozhu , Zhang Shuting , Wu Yili , Staufenbiel Matthias , Cai Fang , Song Weihong
Published: June 2013

Cleavage of amyloid‐β precursor protein (APP) at the Asp1 β‐secretase site of the amyloid‐β protein (Aβ) domain by β‐site Aβ precursor protein‐cleaving enzyme 1 (BACE1) is required for the generation of Aβ, a central component of neuritic plaques in the Alzheimer's disease (AD) brain. In this study, we found that Aβ Glu11 is the major β‐secretase site for cleavage of APP by BACE1 to generate soluble secreted APP (sAPPβ)606 and the C‐terminal membrane‐bound fragment (CTF)β product C89. Cleavage of C89 by γ‐secretase resulted in truncated Aβ generation in a non‐amyloidogenic pathway. A familial AD‐associated Swedish APP mutation adjacent to Aβ Asp1 shifted the major APP β‐secretase cleavage site from Aβ Glu11 to Asp1, resulting in significant increases in sAPPβ596 and CTFβ C99 generation and the C99/89 ratio, in turn leading to increased Aβ production in cultured cells in vitro and transgenic AD model mouse brains in vivo. Furthermore, increased BACE1 expression facilitated APP being processed by the β‐secretase processing pathway rather than the α‐secretase pathway, leading to more Aβ production. Our results suggest that potentiating BACE1 cleavage of APP at both the Asp1 and Glu11 sites, or shifting the cleavage from the Glu11 site to the Asp1 site, could result in increased Aβ production and facilitate neuritic plaque formation. Our study provides new insights into how alteration of BACE1 expression and β‐secretase cleavage site selection could contribute to Alzheimer pathogenesis and the pharmaceutical potential of modulating BACE1 expression and its cleavage site selection.
A ‘danse macabre’: tau and Fyn in STEP with amyloid beta to facilitate induction of synaptic depression and excitotoxicity
Authors: Boehm Jannic
Published: June 2013

Alzheimer's disease, with its two most prominent pathological factors amyloid beta and tau protein, can be described as a disease of the synapse. It therefore comes as little surprise that NMDA receptor‐related synaptic dysfunction had been thought for several years to underlie the synaptic pathophysiology seen in Alzheimer's disease. In this review I will summarise recent evidence showing that the NMDA receptor links the effects of extracellular amyloid beta with intracellular tau protein. Furthermore, the antagonistic roles of Fyn and STEP in NMDA receptor regulation, synaptic plasticity and induction of synaptic depression will be discussed.
Obtaining Diagnostic Classification Model Estimates Using Mplus
Authors: Templin Jonathan , Hoffman Lesa
Published: June 2013

Diagnostic classification models (aka cognitive or skills diagnosis models) have shown great promise for evaluating mastery on a multidimensional profile of skills as assessed through examinee responses, but continued development and application of these models has been hindered by a lack of readily available software. In this article we demonstrate how diagnostic classification models may be estimated as confirmatory latent class models using Mplus, thus bridging the gap between the technical presentation of these models and their practical use for assessment in research and applied settings. Using a sample English test of three grammatical skills, we describe how diagnostic classification models can be phrased as latent class models within Mplus and how to obtain the syntax and output needed for estimation and interpretation of the model parameters. We also have written a freely available SAS program that can be used to automatically generate the Mplus syntax. We hope this work will ultimately result in greater access to diagnostic classification models throughout the testing community, from researchers to practitioners.
Automatic detection of primary motor areas using diffusion MRI tractography: Comparison with functional MRI and electrical stimulation mapping
Authors: Jeong Jeong‐Won , Asano Eishi , Brown Erik C. , Tiwari Vijay N. , Chugani Diane C. , Chugani Harry T.
Published: June 2013

Purpose

As an alternative tool to identify cortical motor areas for planning surgical resection in children with focal epilepsy, the present study proposed a maximum a posteriori probability (MAP) classification of corticospinal tract (CST) visualized by diffusion MR tractography.

Methods

Diffusion‐weighted imaging (DWI) was performed in 17 normally developing children and 20 children with focal epilepsy. An independent component analysis tractography combined with ball–stick model was performed to identify unique CST pathways originating from mouth/lip, finger, and leg areas determined by functional magnetic resonance imaging (fMRI) in healthy children and electrical stimulation mapping (ESM) in children with epilepsy. Group analyses were performed to construct stereotaxic probability maps of primary motor pathways connecting precentral gyrus and posterior limb of internal capsule, and then utilized to design a novel MAP classifier that can sort individual CST fibers associated with three classes of interest: mouth/lip, fingers, and leg. A systematic leave‐one‐out approach was applied to train an optimal classifier. A match was considered to occur if classified fibers contacted or surrounded true areas localized by fMRI and ESM.

Key Findings

It was found that the DWI‐MAP provided high accuracy for the CST fibers terminating in proximity to the localization of fMRI/ESM: 78%/77% for mouth/lip, 77%/76% for fingers, 78%/86% for leg (contact), and 93%/89% for mouth/lip, 91%/89% for fingers, and 92%/88% for leg (surrounded within 2 cm).

Significance

This study provides preliminary evidence that in the absence of fMRI and ESM data, the DWI‐MAP approach can effectively retrieve the locations of cortical motor areas and underlying CST courses for planning epilepsy surgery.
Call Variation in Tufted Titmice (Baeolophus bicolor) in a Distress Context: Potential Sex Differences
Authors: Freeberg Todd M. , Branch Carrie L.
Published: June 2013

Tufted titmice, Baeolophus bicolor, produce calls in the contexts related to threat and approach of, and capture by, a predator. In titmice, these calls transition from the chick‐a‐dee call, used in a wide range of social contexts, to ‘distress’ calls that are produced by birds when captured and held by a predator or human observer. A recent study indicated that titmice modify the note composition of their calls in the presence of such threatening stimuli. Here, we tested whether female and male titmice differed in their calling behavior, as relatively few sex differences have been documented in calls shared by female and male songbirds. Individual titmice were captured in walk‐in treadle traps, and we gradually increased the level of fear or arousal by approaching and finally capturing the bird in the hand. Male titmice produced more chick‐a‐dee calls than females as the level of threat increased, up to the point of capturing the bird in the hand. Furthermore, the note composition of calls produced by males differed from that of calls produced by females. A limitation to our study is that our method did not allow us to rule out the possibility that size or dominance differences, rather than sex, were the main reason for the differences in calling we detected. However, increased size generally was not associated with increased calling. We discuss some possible explanations for variation in distress calling behavior in titmice.
Pore‐scale multiphase flow experiments in bead packs of variable wettability
Authors: Celauro J. G. , Torrealba V. A. , Karpyn Z. T. , Klise K. A. , McKenna S. A.
Published: June 2013

The aim of this experimental study is to investigate the impact of wetting characteristics on multiphase flow, sweep efficiency, and residual fluid distribution in unconsolidated porous media. A sequence of oil and water injections was performed on bead packs with uniform porosity and permeability, but different wettability characteristics. Uniform and mixed‐wet bead packs with varying degree of wettability were fabricated to analyze how the residual saturation profiles and the distribution of fluid phases at the pore scale respond to changes in wettability. X‐ray microtomography was used to visualize and analyze the fluid distribution in each bead pack at the end of oil and brine injection. It was found that sweep efficiency was high for the uniform, strongly wetting glass bead pack. For the intermediate‐wet plastic bead pack, we observed evidence of viscous fingering resulting in degenerating sweep efficiency after water injection. In media with mixed wetting surfaces, the spatial distribution of wettability influenced the topology of the saturation profiles and resulted in larger quantities of disconnected fluid blobs. Results also showed that the average blob size was independent of the average residual saturation. In addition, the difference in saturation conditions preceding each injection affected sweep efficiency. The residual saturation after the 1st displacement was higher than the residual saturation after the 2nd displacement.
Malignant potential of small oncocytic follicular carcinoma/Hürthle cell carcinoma: an institutional experience
Authors: Samulski Teresa Danielle , Bai Shuting , LiVolsi Virginia A , Montone Kathleen , Baloch Zubair
Published: June 2013

Aims

Oncocytic follicular carcinoma/Hürthle cell carcinoma (OFCA/HCCA) is a rare tumour of the thyroid gland that can be associated with an aggressive clinical course. Most OFCA/HCCAs are large; however, tumours ≤20 mm can occur. The aim of this study was to report our experience with OFCA/HCCA diagnosed at our institution.

Methods and results

One hundred and nineteen cases of OFCA/HCCA were included in this study. Data points included age, sex, size of tumour, method of diagnosis, lymph node (LN) status, and clinical follow‐up. The cohort included 37 males and 82 females (average age: 55 years). Preoperative fine‐needle aspiration (FNA) was performed in 73 (61%) cases. Twenty‐five (21%) tumours measured ≤20 mm and 94 (79%) measured >20 mm. Angioinvasion (AI) was present in 48 (40%) cases, and LN metastases (LNMs) in seven (6%) cases; of these, eight (17%) with AI and 1 (2%) with LNMs measured ≤20 mm. Clinical follow‐up was available in 74 (62%) cases (range 12–144 months); 13 (17.5%) developed LNMs and six (8%) regional recurrence. Distant metastases (DMs) were seen in 12 (16%) cases. Two cases with DMs and two with LN recurrence measured ≤20 mm.

Conclusions

Oncocytic follicular carcinoma/Hürthle cell carcinoma (OFCA/HCCA) can present as small (≤20 mm) tumours, and can be associated with AI, LNM, and DM.
Carabids.org – a dynamic online database of ground beetle species traits (Coleoptera, Carabidae)
Authors: Homburg Katharina , Homburg Nils , Schäfer Florian , Schuldt Andreas , Assmann Thorsten
Published: June 2013

Carabids are a species‐rich group (more than 10 000 species in the Palaearctic region) and are intensively studied, inter alia due to their roles as bioindicators and mediators of nutrient flows in ecosystems. Numerous aspects of species' systematics, distribution, evolutionary biology (and phylogeny) and their ecology are well documented for the western Palaearctic and large data sets have already been compiled for macroecological studies.

The online database carabids.org is an enhancement of these data sets and holds species classification and country level data on species distribution range for over 10 000 Palaearctic carabid species. Size and dispersal traits (body and eye size and hind wing development) are available for almost all (over 3400) western Palaearctic carabid species and ecological and life‐history traits (regarding food and habitat preferences as well as time of reproduction and activity) can be offered for most Central European (about 1000) species.

Carabids.org is meant to be a collaborative and interactive project offering a variety of research opportunities. Our project contributes to the rapid expansion and analysis of freely available traits data on species‐rich invertebrates, which will help to advance our understanding of community assembly and functional diversity effects of such taxa across large spatial scales. We would very much appreciate data contributions from carabidologists, other scientists and interested parties.
Musculoskeletal regeneration and its implications for the treatment of tendinopathy
Authors: Sereysky Jedd B. , Flatow Evan L. , Andarawis‐Puri Nelly
Published: June 2013

Tendinopathies are common muskoloskeletal injuries that lead to pain and disability. Development and pathogenesis of tendinopathy is attributed to progressive pathological changes to the structure, function, and biology of tendon. The nature of this disease state, whether acquired by acute or chronic injury, is being actively investigated. Scarring, disorganized tissue, and loss of function characterize adult tendon healing. Recent work from animal models has begun to reveal the potential for adult mammalian tendon regeneration, the replacement of diseased with innate tissue. This review discusses what is known about musculoskeletal regeneration from a molecular perspective and how these findings can be applied to tendinopathy. Non‐mammalian and mammalian models are discussed with emphasis on the potential of Murphy Roths Large mice to serve as a model of adult tendon regeneration. Comparison of regeneration in non‐mammals, foetal mammals and adult mammals emphasizes distinctly different contributing factors to effective regeneration.
Relation of IL‐6, IL‐13 and IL‐15 gene polymorphisms to the rheumatoid factors, anti‐CCP and other measures of rheumatoid arthritis activity
Authors: Pavkova Goldbergova M. , Nemec P. , Lipkova J. , Jarkovsky J. , Gatterova J. , Ambrozkova D. , Vasku A. , Soucek M. , Pavek N.
Published: June 2013

The aim of the study was to examine the relation between polymorphisms and serum levels of selected cytokines (IL‐6, IL‐13 and IL‐15), production of autoantibodies and factors describing rheumatoid arthritis (RA), such as DAS28 and Total Sharp Score. A total of 156 patients with RA according to the ACR criteria, and 200 control subjects were recruited into the study. The measurements of CRP, anti‐CCP, the presence of rheumatoid factors (RFs), radiographs of both hands with calculation of Total Sharp Score (TSS) and DAS28 were obtained from all patients with RA. In total, five polymorphisms in genes coding cytokines (IL‐6, IL‐13 and IL‐15) were detected. The levels of these selected cytokines were measured in serum using ELISA method. A significant difference in allele frequencies between patients with RA and controls was observed for IL‐15 ‐267C/T polymorphism. A higher prevalence of heterozygote variants of IL‐15 polymorphisms (14035A/T and ‐267C/T) in the RF IgG– and RF IgA–negative subgroups was observed. Furthermore, the association of polymorphisms in gene for IL‐15 with circulating level of IL‐15 (14035A/T and 367G/A) and with total RF and Ig‐specific RFs (‐267C/T) was found. The relation of IL‐15 to RFs IgA, IgM, IgG and the measure of DAS28 was proved. The frequency of the T allele of the IL‐13 polymorphism ‐1112C/T was higher in subgroup with faster progression of the disease (TSS/month ≥ 0.1). In conclusion, we present an association of IL‐15 gene polymorphisms with the RFs including subtypes (RF, IgG, IgA) underlined by the relation of increased IL‐15 levels in circulation to RFs.
HIV and co‐infections
Authors: Chang Christina C. , Crane Megan , Zhou JingLing , Mina Michael , Post Jeffrey J. , Cameron Barbara A. , Lloyd Andrew R. , Jaworowski Anthony , French Martyn A. , Lewin Sharon R.
Published: June 2013

Despite significant reductions in morbidity and mortality secondary to availability of effective combination anti‐retroviral therapy (cART), human immunodeficiency virus (HIV) infection still accounts for 1.5 million deaths annually. The majority of deaths occur in sub‐Saharan Africa where rates of opportunistic co‐infections are disproportionately high. In this review, we discuss the immunopathogenesis of five common infections that cause significant morbidity in HIV‐infected patients globally. These include co‐infection with Mycobacterium tuberculosis, Cryptococcus neoformans, hepatitis B virus, hepatitis C virus, and Plasmodium falciparum. Specifically, we review the natural history of each co‐infection in the setting of HIV, the specific immune defects induced by HIV, the effects of cART on the immune response to the co‐infection, the pathogenesis of immune restoration disease (IRD) associated with each infection, and advances in the areas of prevention of each co‐infection via vaccination. Finally, we discuss the opportunities and gaps in knowledge for future research.
Immune restoration after antiretroviral therapy: the pitfalls of hasty or incomplete repairs
Authors: Wilson Eleanor M. P. , Sereti Irini
Published: June 2013

Antiretroviral therapy (ART) is a life‐saving intervention in human immunodeficiency virus (HIV) infection. Immune restoration after ART dramatically reduces the incidence and severity of opportunistic diseases and death. On some occasions, immune restoration may be erratic, leading to acute inflammatory responses (known as immune reconstitution inflammatory syndrome) shortly after ART initiation, or incomplete, with residual inflammation despite chronic treatment, leading to non‐infectious morbidity and mortality. We propose that ART may not always restore the perfect balance of innate and adaptive immunity in strategic milieus, predisposing HIV‐infected persons to complications of acute or chronic inflammation. The best current strategy for fully successful immune restoration is early antiretroviral therapy, which can prevent acquired immunodeficiency syndrome (AIDS)‐associated events, restrict cell subset imbalances and dysfunction, while preserving structural integrity of lymphoid tissues. Future HIV research should capitalize on innovative techniques and move beyond the static study of T‐cell subsets in peripheral blood or isolated tissues. Improved targeted therapeutic strategies could stem from a better understanding of how HIV perturbs the environmental niches and the mobility and trafficking of cells that affect the dynamic cell‐to‐cell interactions and determine the outcome of innate and adaptive immune responses.
Immune activation and HIV persistence: implications for curative approaches to HIV infection
Authors: Klatt Nichole R. , Chomont Nicolas , Douek Daniel C. , Deeks Steven G.
Published: June 2013

Despite complete or near‐complete suppression of human immunodeficiency virus (HIV) replication with combination antiretroviral therapy, both HIV and chronic inflammation/immune dysfunction persist indefinitely. Untangling the association between the virus and the host immune environment during therapy might lead to novel interventions aimed at either curing the infection or preventing the development of inflammation‐associated end‐organ disease. Chronic inflammation and immune dysfunction might lead to HIV persistence by causing virus production, generating new target cells, enabling infecting of activated and resting target cells, altering the migration patterns of susceptible target cells, increasing the proliferation of infected cells, and preventing normal HIV‐specific clearance mechanisms from function. Chronic HIV production or replication might contribute to persistent inflammation and immune dysfunction. The rapidly evolving data on these issues strongly suggest that a vicious cycle might exist in which HIV persistence causes inflammation that in turn contributes to HIV persistence.
Insights into B cells and HIV‐specific B‐cell responses in HIV‐infected individuals
Authors: Moir Susan , Fauci Anthony S.
Published: June 2013

Human immunodeficiency virus (HIV) disease is associated with dysregulation and dysfunction involving all major lymphocyte populations, including B cells. Such perturbations occur early in the course of infection and are driven in large part by immune activation resulting from ongoing HIV replication leading to bystander effects on B cells. While most of the knowledge regarding immune cell abnormalities in HIV‐infected individuals has been gained from studies conducted on the peripheral blood, it is clear that the virus is most active and most damaging in lymphoid tissues. Here, we discuss B‐cell perturbations in HIV‐infected individuals, focusing on the skewing of B‐cell subsets that circulate in the peripheral blood and their counterparts that reside in lymphoid tissues. This review also highlights recent advances in evaluating HIV‐specific B‐cell responses both in the memory B‐cell compartment, as well as in circulating antibody‐secreting plasmablasts and the more differentiated plasma cells residing in tissues. Finally, we consider how knowledge gained by investigating B cells in HIV‐infected individuals may help inform the development of an effective antibody‐based HIV vaccine.