Technologies for imaging neural activity in large volumes

Neural circuitry has evolved to form distributed networks that act dynamically across large volumes. Collecting data from individual planes, conventional microscopy cannot sample circuitry across large volumes at the temporal resolution relevant to neural circuit function and behaviors. Here, we review emerging technologies for rapid volume imaging of neural circuitry. We focus on two critical challenges: the inertia of optical systems, which limits image speed, and aberrations, which restrict the image volume. Optical sampling time must be long enough to ensure high-fidelity measurements, but optimized sampling strategies and point spread function engineering can facilitate rapid volume imaging of neural activity within this constraint. We also discuss new computational strategies for the processing and analysis of volume imaging data of increasing size and complexity. Together, optical and computational advances are providing a broader view of neural circuit dynamics, and help elucidate how brain regions work in concert to support behavior

Improving data quality in neuronal population recordings

Understanding how the brain operates requires understanding how large sets of neurons function together. Modern recording technology makes it possible to simultaneously record the activity of hundreds of neurons, and technological developments will soon allow recording of thousands or tens of thousands. As with all experimental techniques, these methods are subject to confounds that complicate the interpretation of such recordings, and could lead to erroneous scientific conclusions. Here, we discuss methods for assessing and improving the quality of data from these techniques, and outline likely future directions in this field

Prognostic Factors in Patients with Multiple Recurrences of Well-Differentiated Thyroid Carcinoma

Introduction. Patients with multiple recurrences of well-differentiated thyroid carcinoma (WDTC) have markedly reduced overall survival when compared with those who have ≤1 recurrence of their disease. The purpose of this investigation is to identify prognostic factors for mortality in this subgroup. Methods. Patients with multiple recurrences of WDTC were retrospectively identified from the thyroid cancer database at Mount Sinai Hospital, Toronto (1963–2000). Data on patient, tumor, and recurrence characteristics were collected, and each patient was given a MACIS score. Results. A total of 31 patients were identified (11 male, 20 female; 16–83 years). Using univariate analysis, age >45, stage III/IV disease, distant metastasis, vascular invasion, MACIS score >6, and time to recurrence of <12 months were found to be significant predictors for mortality in this subgroup. Conclusions. Patients with multiple recurrences of WDTC follow a distinct clinical course, marked with multiple treatment failures and a substantial risk of mortality

Nuclear and Cytoplasmic Accumulation of Ep-ICD Is Frequently Detected in Human Epithelial Cancers

BACKGROUND: We previously demonstrated that nuclear and cytoplasmic accumulation of the intracellular domain (Ep-ICD) of epithelial cell adhesion molecule (EpCAM) accompanied by a reciprocal reduction of its extracellular domain (EpEx), occurs in aggressive thyroid cancers. This study was designed to determine whether similar accumulation of Ep-ICD is a common event in other epithelial cancers. METHODOLOGY AND RESULTS: Ten epithelial cancers were immunohistochemically analyzed using Ep-ICD and EpEx domain-specific antibodies. The subcellular localization of EpEx and Ep-ICD in the human colon adenocarcinoma cell line CX-1 was observed using immunofluorescence. Nuclear and cytoplasmic Ep-ICD expression was increased in cancers of the breast (31 of 38 tissues, 82%), prostate (40 of 49 tissues, 82%), head and neck (37 of 57 tissues, 65%) and esophagus (17 of 46 tissues, 37%) compared to their corresponding normal tissues that showed membrane localization of the protein. Importantly, Ep-ICD was not detected in the nuclei of epithelial cells in most normal tissues. High nuclear and cytoplasmic Ep-ICD accumulation also occurred in the other six epithelial cancer types analyzed - lung, colon, liver, bladder, pancreatic, and ovarian. A concomitant reduction in membrane EpEx expression was observed in a subset of all cancer types. Receiver operating characteristic curve analysis revealed nuclear Ep-ICD distinguished breast cancers with 82% sensitivity and 100% specificity and prostate cancers with 82% sensitivity and 78% specificity. Similar findings were observed for cytoplasmic accumulation of Ep-ICD in these cancers. We provide clinical evidence of increased nuclear and cytoplasmic Ep-ICD accumulation and a reduction in membranous EpEx in these cancers. CONCLUSIONS: Increased nuclear and cytoplasmic Ep-ICD was observed in all epithelial cancers analyzed and distinguished them from normal tissues with high-sensitivity, specificity, and AUC. Development of a robust high throughput assay for Ep-ICD will facilitate the determination of its diagnostic, prognostic and therapeutic relevance in epithelial cancers

Advances in the understanding, detection and management of equine strangles

Summary: Streptococcus equi subspecies equi (S. equi) is the causative organism of the upper respiratory disease of equids, strangles, characterised by pyrexia, lymphadenopathy and mucopurulent nasal discharge. Strangles was first reported over 750 years ago and continues to be of significance in equine populations across the globe. This review discusses how S. equi has adapted, the clinical manifestation of strangles, and how clinicians and caregivers can tackle the disease in the future. S. equi evolved from the commensal, and occasionally opportunistic pathogen, Streptococcus equi subspecies zooepidemicus refining its capabilities as it became host restricted. The success of S. equi can be attributed to its ability to cause both acute and persistent infection, the latter occurring in about 10% of those infected. In this carrier state, S. equi persists in the guttural pouch without causing clinical signs, intermittently shedding into the environment, and encountering naïve animals. Insight into the S. equi genome and lifestyle has led to advances in diagnostic assays and the development of a safe and efficacious recombinant‐fusion vaccine, giving clinicians and caregivers the tools to better combat this infection. Alongside rigorous biosecurity protocols and pragmatic control measures such as screening new arrivals for exposure and carrier status, these new technologies demonstrate that strangles can be an increasingly preventable infection

ANZAED eating disorder treatment principles and general clinical practice and training standards

Introduction: Eating disorders are complex to manage, and there is limited guidance around the depth and breadth of knowledge, skills and experience required by treatment providers. The Australia & New Zealand Academy for Eating Disorders (ANZAED) convened an expert group of eating disorder researchers and clinicians to define the clinical practice and training standards recommended for mental health professionals and dietitians providing treatment for individuals with an eating disorder. General principles and clinical practice standards were first developed, after which separate mental health professional and dietitian standards were drafted and collated by the appropriate members of the expert group. The subsequent review process included four stages of consultation and document revision: (1) expert reviewers; (2) a face-to-face consultation workshop attended by approximately 100 health professionals working within the sector; (3) an extensive open access online consultation process; and (4) consultation with key professional and consumer/carer stakeholder organisations. Recommendations: The resulting paper outlines and describes the following eight eating disorder treatment principles: (1) early intervention is essential; (2) co-ordination of services is fundamental to all service models; (3) services must be evidence-based; (4) involvement of significant others in service provision is highly desirable; (5) a personalised treatment approach is required for all patients; (6) education and/or psychoeducation is included in all interventions; (7) multidisciplinary care is required and (8) a skilled workforce is necessary. Seven general clinical practice standards are also discussed, including: (1) diagnosis and assessment; (2) the multidisciplinary care team; (3) a positive therapeutic alliance; (4) knowledge of evidence-based treatment; (5) knowledge of levels of care; (6) relapse prevention; and (7) professional responsibility. Conclusions: These principles and standards provide guidance to professional training programs and service providers on the development of knowledge required as a foundation on which to build competent practice in the eating disorder field. Implementing these standards aims to bring treatment closer to best practice, and consequently improve treatment outcomes, reduce financial cost to patients and services and improve patient quality of life

Hoosiers’ Health in a Changing Climate: A Report from the Indiana Climate Change Impacts Assessment

In the coming decades, Indiana’s changing climate will bring with it higher temperatures, longer heat waves, more extremely hot days and more frequent extreme storm events. Those changes will affect the health of Hoosiers in every part of the state. This report from the Indiana Climate Change Impacts Assessment (IN CCIA) describes historical and future climate-related health impacts that affect Hoosiers

Child feces disposal practices in rural Orissa: a cross sectional study.

BACKGROUND: An estimated 2.5 billion people worldwide lack access to improved sanitation facilities. While large-scale programs in some countries have increased latrine coverage, they sometimes fail to ensure optimal latrine use, including the safe disposal of child feces, a significant source of exposure to fecal pathogens. We undertook a cross-sectional study to explore fecal disposal practices among children in rural Orissa, India in villages where the Government of India's Total Sanitation Campaign had been implemented at least three years prior to the study. METHODS AND FINDINGS: We conducted surveys with heads of 136 households with 145 children under 5 years of age in 20 villages. We describe defecation and feces disposal practices and explore associations between safe disposal and risk factors. Respondents reported that children commonly defecated on the ground, either inside the household (57.5%) for pre-ambulatory children or around the compound (55.2%) for ambulatory children. Twenty percent of pre-ambulatory children used potties and nappies; the same percentage of ambulatory children defecated in a latrine. While 78.6% of study children came from 106 households with a latrine, less than a quarter (22.8%) reported using them for disposal of child feces. Most child feces were deposited with other household waste, both for pre-ambulatory (67.5%) and ambulatory (58.1%) children. After restricting the analysis to households owning a latrine, the use of a nappy or potty was associated with safe disposal of feces (OR 6.72, 95%CI 1.02-44.38) though due to small sample size the regression could not adjust for confounders. CONCLUSIONS: In the area surveyed, the Total Sanitation Campaign has not led to high levels of safe disposal of child feces. Further research is needed to identify the actual scope of this potential gap in programming, the health risk presented and interventions to minimize any adverse effect

Intra- and inter-individual genetic differences in gene expression

Genetic variation is known to influence the amount of mRNA produced by a gene. Given that the molecular machines control mRNA levels of multiple genes, we expect genetic variation in the components of these machines would influence multiple genes in a similar fashion. In this study we show that this assumption is correct by using correlation of mRNA levels measured independently in the brain, kidney or liver of multiple, genetically typed, mice strains to detect shared genetic influences. These correlating groups of genes (CGG) have collective properties that account for 40-90% of the variability of their constituent genes and in some cases, but not all, contain genes encoding functionally related proteins. Critically, we show that the genetic influences are essentially tissue specific and consequently the same genetic variations in the one animal may up-regulate a CGG in one tissue but down-regulate the same CGG in a second tissue. We further show similarly paradoxical behaviour of CGGs within the same tissues of different individuals. The implication of this study is that this class of genetic variation can result in complex inter- and intra-individual and tissue differences and that this will create substantial challenges to the investigation of phenotypic outcomes, particularly in humans where multiple tissues are not readily available.&#xd;&#xa;&#xd;&#xa