751 research outputs found

    The role of zebrafish (Danio rerio) in dissecting the genetics and neural circuits of executive function

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    Zebrafish have great potential to contribute to our understanding of behavioural genetics and thus to contribute to our understanding of the aetiology of psychiatric disease. However, progress is dependent upon the rate at which behavioural assays addressing complex behavioural phenotypes are designed, reported and validated. Here we critically review existing behavioural assays with particular focus on the use of adult zebrafish to explore executive processes and phenotypes associated with human psychiatric disease. We outline the case for using zebrafish as models to study impulse control and attention, discussing the validity of applying extant rodent assays to zebrafish and evidence for the conservation of relevant neural circuits

    Joint IARC/NCI International Cancer Seminar Series Report: Expert consensus on future directions for ovarian carcinoma research

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    Recently, ovarian cancer research has evolved considerably because of the emerging recognition that rather than a single disease, ovarian carcinomas comprise several different histotypes that vary by etiologic origin, risk factors, molecular profiles, therapeutic approaches, and clinical outcome. Despite significant progress in our understanding of the etiologic heterogeneity of ovarian cancer, as well as important clinical advances, it remains the eighth most frequently diagnosed cancer in women worldwide and the most fatal gynecologic cancer. The International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) jointly convened an expert panel on ovarian carcinoma to develop consensus research priorities based on evolving scientific discoveries. Expertise ranged from etiology, prevention, early detection, pathology, model systems, molecular characterization, and treatment/clinical management. This report summarizes the current state of knowledge and highlights expert consensus on future directions to continue advancing etiologic, epidemiologic, and prognostic research on ovarian carcinoma

    Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

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    BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care

    Repeatability and Reproducibility of Decisions by Latent Fingerprint Examiners

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    The interpretation of forensic fingerprint evidence relies on the expertise of latent print examiners. We tested latent print examiners on the extent to which they reached consistent decisions. This study assessed intra-examiner repeatability by retesting 72 examiners on comparisons of latent and exemplar fingerprints, after an interval of approximately seven months; each examiner was reassigned 25 image pairs for comparison, out of total pool of 744 image pairs. We compare these repeatability results with reproducibility (inter-examiner) results derived from our previous study. Examiners repeated 89.1% of their individualization decisions, and 90.1% of their exclusion decisions; most of the changed decisions resulted in inconclusive decisions. Repeatability of comparison decisions (individualization, exclusion, inconclusive) was 90.0% for mated pairs, and 85.9% for nonmated pairs. Repeatability and reproducibility were notably lower for comparisons assessed by the examiners as “difficult” than for “easy” or “moderate” comparisons, indicating that examiners' assessments of difficulty may be useful for quality assurance. No false positive errors were repeated (n = 4); 30% of false negative errors were repeated. One percent of latent value decisions were completely reversed (no value even for exclusion vs. of value for individualization). Most of the inter- and intra-examiner variability concerned whether the examiners considered the information available to be sufficient to reach a conclusion; this variability was concentrated on specific image pairs such that repeatability and reproducibility were very high on some comparisons and very low on others. Much of the variability appears to be due to making categorical decisions in borderline cases

    A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

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    We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

    Safety of liver resection and effect on quality of life in patients with benign hepatic disease: Single center experience

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    <p>Abstract</p> <p>Background</p> <p>Although liver resection has long been established for selected patients with benign hepatic disease, the success of surgical treatment of these patients cannot be evaluated exclusively through postoperative morbidity and mortality. Therefore, the aim of the study was to prove the safety of liver resection in the treatment of benign liver tumors and to evaluate the effect of surgical treatment on the patients' qauality of life.</p> <p>Methods</p> <p>A total of 146 patients who underwent liver resection because of benign liver tumors were included in this study. Postoperative outcome was assessed and patients evaluated their quality of life before surgery and at the present time using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ C-30).</p> <p>Results</p> <p>The rate of serious (> grade 2) complications was 4.1% with no postoperative death. The quality of life assessment revealed an overall improvement of general health status after resection (0.7 vs. 0.56, p < 0.001) and additionally a significant reduction of 6 out of 9 symptoms. Furthermore, compelling benefits in the patients' social and emotional coping could be detected after surgery.</p> <p>Conclusions</p> <p>Liver resection for benign liver disease is a safe procedure and leads to a significant improvement of quality of life in selected patients.</p

    Supplementation of Male Pheromone on Rock Substrates Attracts Female Rock Lizards to the Territories of Males: A Field Experiment

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    Background: Many animals produce elaborated sexual signals to attract mates, among them are common chemical sexual signals (pheromones) with an attracting function. Lizards produce chemical secretions for scent marking that may have a role in sexual selection. In the laboratory, female rock lizards (Iberolacerta cyreni) prefer the scent of males with more ergosterol in their femoral secretions. However, it is not known whether the scent-marks of male rock lizards may actually attract females to male territories in the field. Methodology/Principal Findings: In the field, we added ergosterol to rocks inside the territories of male lizards, and found that this manipulation resulted in increased relative densities of females in these territories. Furthermore, a higher number of females were observed associated to males in manipulated plots, which probably increased mating opportunities for males in these areas. Conclusions/Significance: These and previous laboratory results suggest that female rock lizards may select to settle in home ranges based on the characteristics of scent-marks from conspecific males. Therefore, male rock lizards might attract more females and obtain more matings by increasing the proportion of ergosterol when scent-marking their territories. However, previous studies suggest that the allocation of ergosterol to secretions may be costly and only high quality male

    Stab Injury to the Preauricular Region With Laceration of the External Carotid Artery Without Involvement of the Facial Nerve: a Case Report

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    BACKGROUND: Open injuries to the face involving the external carotid artery are uncommon. These injuries are normally associated with laceration of the facial nerve because this nerve is more superficial than the external carotid artery. Hence, external carotid artery lesions are usually associated with facial nerve dysfunction. We present an unusual case report in which the patient had an injury to this artery with no facial nerve compromise. CASE PRESENTATION: A 25-year-old Portuguese man sustained a stab wound injury to his right preauricular region with a broken glass. Immediate profuse bleeding ensued. Provisory tamponade of the wound was achieved at the place of aggression by two off-duty doctors. He was initially transferred to a district hospital, where a large arterial bleeding was observed and a temporary compressive dressing was applied. Subsequently, the patient was transferred to a tertiary hospital. At admission in the emergency room, he presented a pulsating lesion in the right preauricular region and slight weakness in the territory of the inferior buccal branch of the facial nerve. The physical examination suggested an arterial lesion superficial to the facial nerve. However, in the operating theater, a section of the posterior and lateral flanks of the external carotid artery inside the parotid gland was identified. No lesion of the facial nerve was observed, and the external carotid artery was repaired. To better understand the anatomical rationale of this uncommon clinical case, we dissected the preauricular region of six cadavers previously injected with colored latex solutions in the vascular system. A small triangular space between the two main branches of division of the facial nerve in which the external carotid artery was not covered by the facial nerve was observed bilaterally in all cases. CONCLUSIONS: This clinical case illustrates that, in a preauricular wound, the external carotid artery can be injured without facial nerve damage. However, no similar description was found in the reviewed literature, which suggests that this must be a very rare occurrence. According to the dissection study performed, this is due to the existence of a triangular space between the cervicofacial and temporofacial nerve trunks in which the external carotid artery is not covered by the facial nerve or its branches.info:eu-repo/semantics/publishedVersio

    X-linked inhibitor of apoptosis positive nuclear labeling: a new independent prognostic biomarker of breast invasive ductal carcinoma

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    <p>Abstract</p> <p>Background</p> <p>It's well recognized that X-linked inhibitor of apoptosis (XIAP) was the most potent caspase inhibitor and second mitochondria-derived activator of caspase (Smac) was the antagonist of XIAP. Experiments in vitro identified that down regulation of XIAP expression or applying Smac mimics could sensitize breast cancer cells to chemotherapeutics and promote apoptosis. However, expression status and biologic or prognostic significance of XIAP/Smac in breast invasive ductal carcinoma (IDC) were not clear. The present study aimed to investigate relationship among expression status of XIAP/Smac, apoptosis index (AI), clinicopathologic parameters and prognosis in IDC.</p> <p>Methods</p> <p>Immunohistochemistry and TUNEL experiment were performed to detect expression of XIAP, Smac, ER, PR, HER2 and AI in 102 cases of paraffin-embedded IDC samples respectively. Expression of XIAP/Smac were also detected in limited 8 cases of fresh IDC specimens with Western blot.</p> <p>Results</p> <p>Positive ratio and immunoscore of XIAP was markedly higher than Smac in IDC (<it>P </it>< 0.0001). It was noteworthy that 44 cases of IDC were positive in nuclear for XIAP, but none was for Smac. Expression status of Smac was more prevalent in HER2 positive group than negative group (<it>P </it>< 0.0001) and AI was positively correlated with HER2 protein expression (r<sub>s </sub>= 0.265, <it>P </it>= 0.017). The present study first revealed that XIAP positive nuclear labeling (XIAP-N), but not cytoplasmic staining (XIAP-C), was the apoptotic marker correlated significantly with patients' shortened overall survival (<it>P </it>= 0.039). Survival analysis demonstrated that XIAP-N was a new independent prognostic factor except for patient age and lymph node status.</p> <p>Conclusion</p> <p>Disturbed balance of expression between XIAP and Smac probably contributed to carcinogenesis and XIAP positive nuclear labeling was a new independent prognostic biomarker of breast IDC.</p
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