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Schizophrenia is associated with robust hippocampal volume deficits but subregion volume deficits, their associations with cognition, and contributing genes remain to be determined.
Hippocampal formation (HF) subregion volumes were obtained using FreeSurfer 6.0 from individuals with schizophrenia (n = 176, mean age ± s.d. = 39.0 ± 11.5, 132 males) and healthy volunteers (n = 173, mean age ± s.d. = 37.6 ± 11.3, 123 males) with similar mean age, gender, handedness, and race distributions. Relationships between the HF subregion volume with the largest between group difference, neuropsychological performance, and single-nucleotide polymorphisms were assessed.
This study found a significant group by region interaction on hippocampal subregion volumes. Compared to healthy volunteers, individuals with schizophrenia had significantly smaller dentate gyrus (DG) (Cohen's d = −0.57), Cornu Ammonis (CA) 4, molecular layer of the hippocampus, hippocampal tail, and CA 1 volumes, when statistically controlling for intracranial volume; DG (d = −0.43) and CA 4 volumes remained significantly smaller when statistically controlling for mean hippocampal volume. DG volume showed the largest between group difference and significant positive associations with visual memory and speed of processing in the overall sample. Genome-wide association analysis with DG volume as the quantitative phenotype identified rs56055643 (β = 10.8, p < 5 × 10−8, 95% CI 7.0–14.5) on chromosome 3 in high linkage disequilibrium with MOBP. Gene-based analyses identified associations between SLC25A38 and RPSA and DG volume.
This study suggests that DG dysfunction is fundamentally involved in schizophrenia pathophysiology, that it may contribute to cognitive abnormalities in schizophrenia, and that underlying biological mechanisms may involve contributions from MOBP, SLC25A38, and RPSA.
Schizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions in SZ patients compared with healthy comparison participants (HCs). However, fundamental questions remain regarding the clinical significance of these connectivity abnormalities.
Resting state seed-based functional connectivity was used to investigate thalamus to whole brain connectivity using multi-site data including 183 SZ patients and 178 matched HCs. Statistical significance was based on a voxel-level FWE-corrected height threshold of p < 0.001. The relationships between positive and negative symptoms of SZ and regions of the brain demonstrating group differences in thalamic connectivity were examined.
HC and SZ participants both demonstrated widespread positive connectivity between the thalamus and cortical regions. Compared with HCs, SZ patients had reduced thalamic connectivity with bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had greater thalamic connectivity with multiple sensory-motor regions, including bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity was positively correlated with hallucinations and delusions, while thalamus to cerebellar connectivity was negatively correlated with delusions and bizarre behavior.
Thalamic hyperconnectivity with sensory regions and hypoconnectivity with cerebellar regions in combination with their relationship to clinical features of SZ suggest that thalamic dysconnectivity may be a core neurobiological feature of SZ that underpins positive symptoms.
Adults with tetralogy of Fallot experience atrial tachyarrhythmias; however, there are a few data on the outcomes of radiofrequency ablation. We examined the characteristics, outcome, and predictors of recurrence of atrial tachyarrhythmias after radiofrequency ablation in tetralogy of Fallot patients.
Retrospective data were collected from 2004 to 2013. In total, 56 ablations were performed on 37 patients. We identified two matched controls per case: patients with tetralogy of Fallot but no radiofrequency ablation and not known to have atrial tachyarrhythmias. Acute success was 98%. Left atrial arrhythmias increased in frequency over time. The mean follow-up was 41 months; 78% were arrhythmia-free. Number of cardiac surgeries, age, and presence of atrial fibrillation were predictors of recurrence. Lone cavo-tricuspid isthmus-dependent flutter reduced the likelihood of atrial fibrillation. Right and left atria in patients with tetralogy of Fallot were larger in ablated cases than controls. NYHA class was worse in cases and improved after ablation; baseline status predicted death. Of matched non-ablated controls, a number of them had atrial fibrillation. These patients were excluded from the case–control study but analysed separately. Most of them had died during follow-up, whereas of the matched ablated cases all were alive and the majority in sinus rhythm.
Patients with tetralogy of Fallot and atrial tachyarrhythmias have more dilated atria than those without atrial tachyarrhythmias. Radiofrequency ablation improves functional status. Left atrial ablation is more commonly required with repeat procedures. There is a high prevalence of atrial tachyarrhythmias, particularly atrial fibrillation, in patients with tetralogy of Fallot; early radiofrequency ablation may have a protective effect against this.
Translation of proteins by the ribosome regulates gene expression, with recent results underscoring the importance of translational control. Misregulation of translation underlies many diseases, including cancer and many genetic diseases. Decades of biochemical and structural studies have delineated many of the mechanistic details in prokaryotic translation, and sketched the outlines of eukaryotic translation. However, translation may not proceed linearly through a single mechanistic pathway, but likely involves multiple pathways and branchpoints. The stochastic nature of biological processes would allow different pathways to occur during translation that are biased by the interaction of the ribosome with other translation factors, with many of the steps kinetically controlled. These multiple pathways and branchpoints are potential regulatory nexus, allowing gene expression to be tuned at the translational level. As research focus shifts toward eukaryotic translation, certain themes will be echoed from studies on prokaryotic translation. This review provides a general overview of the dynamic data related to prokaryotic and eukaryotic translation, in particular recent findings with single-molecule methods, complemented by biochemical, kinetic, and structural findings. We will underscore the importance of viewing the process through the viewpoints of regulation, translational control, and heterogeneous pathways.
Historically, American Indian/Alaska Native (AI/AN) populations have suffered excess morbidity and mortality from influenza. We investigated the risk factors for death from 2009 pandemic influenza A(H1N1) in persons residing in five states with substantial AI/AN populations. We conducted a case-control investigation using pandemic influenza fatalities from 2009 in Alaska, Arizona, New Mexico, Oklahoma and Wyoming. Controls were outpatients with influenza. We reviewed medical records and interviewed case proxies and controls. We used multiple imputation to predict missing data and multivariable conditional logistic regression to determine risk factors. We included 145 fatal cases and 236 controls; 22% of cases were AI/AN. Risk factors (P < 0·05) included: older age [adjusted matched odds ratio (mOR) 3·2, for >45 years vs. <18 years], pre-existing medical conditions (mOR 7·1), smoking (mOR 3·0), delayed receipt of antivirals (mOR 6·5), and barriers to healthcare access (mOR 5·3). AI/AN race was not significantly associated with death. The increased influenza mortality in AI/AN individuals was due to factors other than racial status. Prevention of influenza deaths should focus on modifiable factors (smoking, early antiviral use, access to care) and identifying high-risk persons for immunization and prompt medical attention.
At the present moment, zinc oxide is primarily being used as an electronic material for low-field thin-film transistor and transparent conducting oxide device applications. In this paper, we present some recent results on the steady-state electron transport within zinc oxide suggesting that this material may also be considered as an alternative material to gallium nitride for high-power and high-frequency electron device applications. The expected device performance that may be obtained from zinc oxide-based devices is then projected and contrasted with that expected from gallium nitride-based devices. It is shown that zinc oxide-based devices have a slight advantage when compared with the case of gallium nitride.
Hospitalizations for acute bacterial skin and skin structure infection (ABSSSI) are common. Optimizing antibiotic use for ABSSSIs requires an understanding of current management. The objective of this study was to evaluate antibiotic prescribing practices and factors affecting prescribing in a diverse group of hospitals
Multicenter, retrospective cohort study.
Seven community and academic hospitals.
Children and adults hospitalized between June 2010 and May 2012 for cellulitis, wound infection, or cutaneous abscess were eligible. The primary endpoint was a composite of 2 prescribing practices representing potentially avoidable antibiotic exposure: (1) use of antibiotics with a broad spectrum of activity against gram-negative bacteria or (2) treatment duration greater than 10 days.
A total of 533 cases were included: 320 with nonpurulent cellulitis, 44 with wound infection or purulent cellulitis, and 169 with abscess. Of 492 cases with complete prescribing data, the primary endpoint occurred in 394 (80%) cases and varied significantly across hospitals (64%–97%; P < .001). By logistic regression, independent predictors of the primary endpoint included wound infection or purulent cellulitis (odds ratio [OR], 5.12 [95% confidence interval (CI)], 1.46–17.88), head or neck involvement (OR, 2.83 [95% CI, 1.17–6.82]), adult cases (OR, 2.20 [95% CI, 1.18–4.11]), and admission to a community hospital (OR, 1.90 [95% CI, 1.05–3.44]).
Among patients hospitalized for ABSSSI, use of antibiotics with broad gram-negative activity or treatment courses longer than 10 days were common. There may be substantial opportunity to reduce antibiotic exposure through shorter courses of therapy targeting gram-positive bacteria.
Infect Control Hosp Epidemiol 2014;35(10):1241–1250
Numerous techniques have been described to manage the skin and other soft tissues during bone-anchored hearing aid insertion. Previously, generally accepted techniques have sometimes led to distressing alopecia and soft tissue defects. Now, some surgeons are rejecting the originally described split skin flap in favour of a less invasive approach.
To investigate bone-anchored hearing aid placement utilising a single, linear incision with either no or minimal underlying soft tissue reduction.
Patients and methods:
Thirty-four adults were prospectively enrolled to undergo single-stage bone-anchored hearing aid placement with this modified technique. A small, linear incision was used at the standard position and carried down through the periosteum. Standard technique was then followed with placement of an extended length abutment. Patients were reviewed regularly to assess wound healing, including evaluation with Holgers' scale.
Only 14.7 per cent of patients had a reaction score of 2 or higher. Most complications were limited to minor skin reactions that settled with silver nitrate cautery and/or antibiotics. None required revision surgery for tissue overgrowth, and there were no implant failures.
Our results suggest this to be a simple and effective insertion technique with favourable cosmesis and patient satisfaction.
Although extensive research and practice have focused on understanding and improving performance management systems in organizations, the formula for effective performance management remains elusive. We propose that a significant part of the problem is that performance management has been reduced to prescribed steps within formal administrative systems that are disconnected from the day-to-day activities that determine performance management effectiveness (e.g., communicating clear work expectations, setting short-term objectives and deadlines, and providing continual guidance). We argue that interventions to improve performance management should cease their exclusive focus on reinventing formal system features. Although well-developed tools and systems can facilitate performance management, these alone do not yield effective performance management. In lieu of making further changes to formal performance management systems, we argue for devoting more attention to improving manager–employee communication and aspects of the manager–employee relationship and propose an approach we believe holds promise for improving performance management processes in organizations.
In our recent focal article, we proposed that a fundamental change is needed in how performance management is implemented and viewed. Rather than attempting to improve the effectiveness of performance management by changing features of the formal system (e.g., steps, tools, and processes), we recommended increased focus on improving manager–employee communication and aspects of the manager–employee relationship that are foundational for effective performance management. Our article generated a number of thoughtful and engaging commentaries. In this commentary, we respond to several themes raised in the commentaries and relate them to the recommendations we made for improving performance management processes in organizations.
From January 2009 to May 2010, 436 faecal samples from patients with diarrhoeal illness in Southern Ireland were identified as Campylobacter genus-positive by an automated multiplex PCR; however, 204 (46·8%) of these samples were culture-negative for campylobacters. A combination of Campylobacter-specific uniplex PCR and 16S rRNA sequencing confirmed the presence of Campylobacter DNA in 191 (93·6%) of the culture-negative samples. Species-specific PCR identified C. jejuni (50·7%) C. ureolyticus (41%) and C. coli (5·7%) as the most prevalent species while C. fetus, C. upsaliensis, C. hyointestinalis and C. lari accounted for 10% of culture-negative samples; mixed Campylobacter spp. were detected in 11% of samples. We conclude that non-culturable Campylobacter spp. are responsible for a considerable proportion of human enteritis and the true incidence of infection is likely to be significantly underestimated where conventional Campylobacter culture methods are used in isolation.
Individuals with Alzheimer's disease (AD) experience difficulties with socioemotional functioning, and it has been proposed that cognitive disinhibition may be one potential mechanism that contributes to difficulties in this area. To test this possibility, twenty individuals with AD and 20 demographically matched controls were administered self-report measures of depression, emotion regulation and empathy, in addition to a behavioral measure that has proven to be very sensitive to inhibitory failures (the Hayling Sentence Completion Test). Relative to controls AD participants exhibited increased inhibitory failures on the Hayling, and self-reported significantly reduced cognitive empathy, but did not differ with respect to affective empathy, depression or perceived capacity for emotion regulation. Controlling for general cognitive status, in the AD (but not the control) group, reduced cognitive inhibition was associated with lower levels of depression. The theoretical and practical implications of these results are discussed. (JINS, 2007, 13, 1060–1064.)