Summary statistics in auditory perception

Sensory signals are transduced at high resolution, but their structure must be stored in a more compact format. Here we provide evidence that the auditory system summarizes the temporal details of sounds using time-averaged statistics. We measured discrimination of 'sound textures' that were characterized by particular statistical properties, as normally result from the superposition of many acoustic features in auditory scenes. When listeners discriminated examples of different textures, performance improved with excerpt duration. In contrast, when listeners discriminated different examples of the same texture, performance declined with duration, a paradoxical result given that the information available for discrimination grows with duration. These results indicate that once these sounds are of moderate length, the brain's representation is limited to time-averaged statistics, which, for different examples of the same texture, converge to the same values with increasing duration. Such statistical representations produce good categorical discrimination, but limit the ability to discern temporal detail.Howard Hughes Medical Institut

Clinical Implication of Targeting of Cancer Stem Cells

The existence of cancer stem cells (CSCs) is receiving increasing interest particularly due to its potential ability to enter clinical routine. Rapid advances in the CSC field have provided evidence for the development of more reliable anticancer therapies in the future. CSCs typically only constitute a small fraction of the total tumor burden; however, they harbor self-renewal capacity and appear to be relatively resistant to conventional therapies. Recent therapeutic approaches aim to eliminate or differentiate CSCs or to disrupt the niches in which they reside. Better understanding of the biological characteristics of CSCs as well as improved preclinical and clinical trials targeting CSCs may revolutionize the treatment of many cancers. Copyright (c) 2012 S. Karger AG, Base

Long-term survival after initial hospital admission for peripheral arterial disease in the lower extremities

ABSTRACT: Background As the population ages, peripheral arterial disease (PAD) in the lower extremities will become a larger public health problem. Awareness in patients as well clinicians of the high risk of morbidity and mortality is important but seems currently low. Insights in absolute mortality risks following admission for PAD in the lower extremities can be useful to improve awareness as they are easy to interpret. Methods A nationwide cohort of 4,158 patients with an initial admission for PAD in the lower extremities was identified through linkage of the national hospital and population register in 1997 and 2000. Results Over 60% of 4,158 patients were men. 28 days, 1 year and 5 year mortality risk were 2.4%, 10.3% and 31.0% for men and 3.5%, 10.4% and 27.4% for women. Coronary heart disease and stroke were frequent cause of death. Five years mortality risk was higher for men compared to women (HR 1.36, 95% CI 1.21-1.53). Conclusions Our findings demonstrate that, 5 year mortality risk is high, especially in men and comparable to that of patients admitted for acute myocardial infarction or ischemic stroke. Though, in general population the awareness of the severity of PAD in the lower extremities is significantly lower than that for any other cardiovascular disease and it seems that cardiovascular risk factor management for prevention in PAD patients is very modes

Changes in articular cartilage after meniscectomy and meniscus replacement using a biodegradable porous polymer implant

Purpose: To evaluate the long-term effects of implantation of a biodegradable polymer meniscus implant on articular cartilage degeneration and compare this to articular cartilage degeneration after meniscectomy. Methods: Porous polymer polycaprolacton-based polyurethane meniscus implants were implanted for 6 or 24 months in the lateral compartment of Beagle dog knees. Contralateral knees were meniscectomized, or left intact and served as controls. Articular cartilage degeneration was evaluated in detail using India ink staining, routine histology, immunochemistry for denatured (Col2-¾M) and cleaved (Col2-¾Cshort) type II collagen, Mankin’s grading system, and cartilage thickness measurements. Results: Histologically, fibrillation and substantial immunohistochemical staining for both denatured and cleaved type II collagen were found in all three treatment groups. The cartilage of the three groups showed identical degradation patterns. In the 24 months implant group, degradation appeared to be more severe when compared to the 6 months implant group and meniscectomy group. Significantly more cartilage damage (India ink staining, Mankin’s grading system, and cartilage thickness measurements) was found in the 24 months implant group compared to the 6 months implant group and meniscectomy group. Conclusion: Degradation of the cartilage matrix was the result of both mechanical overloading as well as localized cell-mediated degradation. The degeneration patterns were highly variable between animals. Clinical application of a porous polymer implant for total meniscus replacement is not supported by this study.

Health-seeking behaviour of human brucellosis cases in rural Tanzania

<p>Abstract</p> <p>Background</p> <p>Brucellosis is known to cause debilitating conditions if not promptly treated. In some rural areas of Tanzania however, practitioners give evidence of seeing brucellosis cases with symptoms of long duration. The purpose of this study was to establish health-seeking behaviour of human brucellosis cases in rural Tanzania and explore the most feasible ways to improve it.</p> <p>Methods</p> <p>This was designed as a longitudinal study. Socio-demographic, clinical and laboratory data were collected from patients who reported to selected hospitals in rural northern Tanzania between June 2002 and April 2003. All patients with conditions suspicious of brucellosis on the basis of preliminary clinical examination and history were enrolled into the study as brucellosis suspects. Blood samples were taken and tested for brucellosis using the Rose-Bengal Plate Test (RBPT) and other agglutination tests available at the health facilities and the competitive ELISA (c-ELISA) test at the Veterinary Laboratory Agencies (VLA) in the UK. All suspects who tested positive with the c-ELISA test were regarded as brucellosis cases. A follow-up of 49 cases was made to collect data on health-seeking behaviour of human brucellosis cases.</p> <p>Results</p> <p>The majority of cases 87.7% gave a history of going to hospital as the first point of care, 10.2% purchased drugs from a nearby drug shop before going to hospital and 2% went to a local traditional healer first. Brucellosis cases delayed going to hospital with a median delay time of 90 days, and with 20% of the cases presenting to hospitals more than a year after the onset of symptoms. Distance to the hospital, keeping animals and knowledge of brucellosis were significantly associated with patient delay to present to hospital.</p> <p>Conclusion</p> <p>More efforts need to be put on improving the accessibility of health facilities to the rural poor people who succumb to most of the diseases including zoonoses. Health education on brucellosis in Tanzania should also stress the importance of early presentation to hospitals for prompt treatment.</p

The role of chemotherapy in the management of newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline

TARGET POPULATION: This recommendation applies to adults with newly diagnosed brain metastases; however, the recommendation below does not apply to the exquisitely chemosensitive tumors, such as germinomas metastatic to the brain. RECOMMENDATION: Should patients with brain metastases receive chemotherapy in addition to whole brain radiotherapy (WBRT)? Level 1 Routine use of chemotherapy following WBRT for brain metastases has not been shown to increase survival and is not recommended. Four class I studies examined the role of carboplatin, chloroethylnitrosoureas, tegafur and temozolomide, and all resulted in no survival benefit. Two caveats are provided in order to allow the treating physician to individualize decision-making: First, the majority of the data are limited to non small cell lung (NSCLC) and breast cancer; therefore, in other tumor histologies, the possibility of clinical benefit cannot be absolutely ruled out. Second, the addition of chemotherapy to WBRT improved response rates in some, but not all trials; response rate was not the primary endpoint in most of these trials and end-point assessment was non-centralized, non-blinded, and post-hoc. Enrollment in chemotherapy-related clinical trials is encouraged

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Screen or not to screen for peripheral arterial disease: Guidance from a decision model

__Abstract__ Background: Asymptomatic Peripheral Arterial Disease (PAD) is associated with greater risk of acute cardiovascular events. This study aims to determine the cost-effectiveness of one time only PAD screening using Ankle Brachial Index (ABI) test and subsequent anti platelet preventive treatment (low dose aspirin or clopidogrel) in individuals at high risk for acute cardiovascular events compared to no screening and no treatment using decision analytic modelling. Methods. A probabilistic Markov model was developed to evaluate the life time cost-effectiveness of the strategy of selective PAD screening and consequent preventive treatment compared to no screening and no preventive treatment. The analysis was conducted from the Dutch societal perspective and to address decision uncertainty, probabilistic sensitivity analysis was performed. Results were based on average values of 1000 Monte Carlo simulations and using discount rates of 1.5% and 4% for effects and costs respectively. One way sensitivity analyses were performed to identify the two most influential model parameters affecting model outputs. Then, a two way sensitivity analysis was conducted for combinations of values tested for these two most influential parameters. Results: For the PAD screening strategy, life years and quality adjusted life years gained were 21.79 and 15.66 respectively at a lifetime cost of 26,548 Euros. Compared to no screening and treatment (20.69 life years, 15.58 Quality Adjusted Life Ye

CCL3L1 copy number, CCR5 genotype and susceptibility to tuberculosis

Background: Tuberculosis is a major infectious disease and functional studies have provided evidence that both the chemokine MIP-1α and its receptor CCR5 play a role in susceptibility to TB. Thus by measuring copy number variation of CCL3L1, one of the genes that encode MIP-1α, and genotyping a functional promoter polymorphism -2459A > G in CCR5 (rs1799987) we investigate the influence of MIP-1α and CCR5, independently and combined, in susceptibility to clinically active TB in three populations, a Peruvian population (n = 1132), a !Xhosa population (n = 605) and a South African Coloured population (n = 221). The three populations include patients with clinically diagnosed pulmonary TB, as well as other, less prevalent forms of extrapulmonary TB. Methods and results: Copy number of CCL3L1 was measured using the paralogue ratio test and exhibited ranges between 0–6 copies per diploid genome (pdg) in Peru, between 0–12 pdg in !Xhosa samples and between 0–10 pdg in South African Coloured samples. The CCR5 promoter polymorphism was observed to differ significantly in allele frequency between populations (*A; Peru f = 0.67, !Xhosa f = 0.38, Coloured f = 0.48). Conclusions: The case–control association studies performed however find, surprisingly, no evidence for an influence of variation in genes coding for MIP-1α or CCR5 individually or together in susceptibility to clinically active TB in these populations

Does delay in diagnosing colorectal cancer in symptomatic patients affect tumor stage and survival? A population-based observational study

<p>Abstract</p> <p>Background</p> <p>Diagnosing colorectal cancer (CRC) at an early stage improves survival. To what extent any delay affects outcome once patients are symptomatic is still unclear.</p> <p>Our objectives were to evaluate the association between diagnostic delay and survival in symptomatic patients with early stage CRC and late stage CRC.</p> <p>Methods</p> <p>Prospective population-based observational study evaluating daily clinical practice in Northern Holland. Diagnostic delay was determined through questionnaire-interviews. Dukes' stage was classified into two groups: early stage (Dukes A or B) and late stage (Dukes C or D) cancer. Patients were followed up for 3.5 years after diagnosis.</p> <p>Results</p> <p>In total, 272 patients were available for analysis. Early stage CRC was present in 136 patients while 136 patients had late stage CRC. The mean total diagnostic delay (SE) was 31 (1.5) weeks in all CRC patients. No significant difference was observed in the mean total diagnostic delay in early versus late stage CRC (<it>p </it>= 0.27).</p> <p>In early stage CRC, no difference in survival was observed between patients with total diagnostic delay shorter and longer than the median (Kaplan-Meier, log-rank <it>p </it>= 0.93).</p> <p>In late stage CRC, patients with a diagnostic delay shorter than the median had a shorter survival than patients with a diagnostic delay longer than the median (log-rank <it>p </it>= 0.01). In the multivariate Cox regression model with survival as dependent variable and median delay, age, open access endoscopy, number and type of symptoms as independent variables, the odd's ratio for survival in patients with long delay (>median) versus short delay (≤median) was 1.8 (95% confidence interval (CI) 1.1 to 3.0; <it>p </it>= 0.01). Tumor-site was not associated with patient survival. When separating late stage CRC in Dukes C and Dukes D tumors, a shorter delay was associated with a shorter survival in Dukes D tumors only and not in Dukes C tumors.</p> <p>Conclusion</p> <p>In symptomatic CRC patients, a longer diagnostic and therapeutic delay in routine clinical practice was not associated with an adverse effect on survival. The time to CRC diagnosis and initiation of treatment did not differ between early stage and late stage colorectal cancer.</p