Potential distribution of two species in the medically important Anopheles minimus complex (Diptera: Culicidae)

Anopheles minimus Theobald (=An. minimus A) and possibly Anopheles harrisoni Harbach & Manguin (=An. minimus C) are important malaria vector species in the Minimus Complex in Southeast Asia. The distributions of these species are poorly known, although detailed information could benefit malaria vector incrimination and control. We used published collection records of these species and environmental geospatial data to construct consensus ecological niche models (ENM) of each species' potential geographic distribution. The status of the Indian taxon An. fluviatilis S as a species distinct from An. harrisoni has been debated in the literature, so we tested for differentiation in ecological niche characteristics. The predicted potential distribution of An. minimus is more southerly than that of An. harrisoni: Southeast Asia is predicted to be more suitable for An. minimus, and China and India are predicted more suitable for An. harrisoni, so An. harrisoni seems to dominate under cooler conditions. The distribution of An. minimus is more continuous than that of An. harrisoni: disjunction in the potential distribution of the latter is suggested between India and Southeast Asia Anopheles fluviatilis S occurrences are predicted within the An. harrisoni ecological potential, so we do not document ecological differentiation that might reject conspecificity. Overall, model predictions offer a synthetic view of the distribution of this species complex across the landscapes of southern and eastern Asia.     

Reduction in Postoperative High-Density Lipoprotein Cholesterol Levels in Children Undergoing the Fontan Operation

Despite the emerging relevance of high-density lipoprotein (HDL) in the inflammatory cascade and vascular barrier integrity, HDL levels in children undergoing cardiac surgery are unexplored. As a measure of HDL levels, the HDL-cholesterol (HDL-C) in single-ventricle patients was quantified before and after the Fontan operation, and it was determined whether relationships existed between the duration and the type of postoperative pleural effusions. The study prospectively enrolled 12 children undergoing the Fontan operation. Plasma HDL-C levels were measured before and after cardiopulmonary bypass. The outcome variables of interest were the duration and type of chest tube drainage (chylous vs. nonchylous). The Kendall rank correlation coefficient and the Wilcoxon rank sum test were used. There were 11 complete observations. The median preoperative HDL-C level for all the subjects was 30?mg/dl (range, 24-53?mg/dl), and the median postcardiopulmonary bypass level was 21?mg/dl (range, 14-46?mg/dl) (p?=?0.004). There was a tendency toward a moderate inverse correlation (-0.42) between the postcardiopulmonary bypass HDL-C level and the duration of chest tube drainage, but the result was not statistically significant (p?=?0.07). In the chylous effusion group, the median postcardiopulmonary bypass HDL-C tended to be lower (16 vs. 23?mg/dl; p?=?0.09). After the Fontan operation, the plasma HDL-C levels in children are significantly reduced. It is reasonable to conclude that the reduction in HDL-C reflects reduced plasma levels of HDL particles, which may have pertinent implications in postoperative pleural effusions given the antiinflammatory and endothelial barrier functions of HDL.     

The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry

Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus is determined by a combination of environmental and genetic factors, which include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2 cannot explain the clustering of type 1 diabetes in families, and a role for other genes is inferred. In the present report we describe linkage and association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong candidate gene for T cell- mediated autoimmune disease because it encodes a T cell receptor that mediates T cell apoptosis and is a vital negative regulator of T cell activation. In addition, we provide supporting evidence that CTLA-4 is associated with susceptibility to Graves' disease, another organ- specific autoimmune disease.      

Genomic and mutational profiling of ductal carcinomas in situ and matched adjacent invasive breast cancers reveals intra-tumour genetic heterogeneity and clonal selection

The mechanisms underlying the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) of the breast are yet to be fully elucidated. Several hypotheses have been put forward to explain the progression from DCIS to IDC, including the selection of a subpopulation of cancer cells with specific genetic aberrations, and the acquisition of new genetic aberrations or non-genetic mechanisms mediated by the tumour microenvironment. To determine whether synchronously diagnosed ipsilateral DCI and IDCs have modal populations with distinct repertoires of gene copy number aberrations and mutations in common oncogenes, matched frozen samples of DCIS and IDC were retrieved from 13 patients and subjected to microarray-based comparative genomic hybridization (aCGH) and Sequenom MassARRAY (Oncocarta v 1.0 panel). Fluorescence in situ hybridization and Sanger sequencing were employed to validate the aCGH and Sequenom findings, respectively. Although the genomic profiles of matched DCI and IDCs were similar, in three of 13 matched pairs amplification of distinct loci (ie 1q41, 2q24.2, 6q22.31, 7q11.21, 8q21.2 and 9p13.3) was either restricted to, or more prevalent in, the modal population of cancer cells of one of the components. Sequenom MassARRAY identified PIK3CA mutations restricted to the DCIS component in two cases, and in a third case the frequency of the PIK3CA mutant allele reduced from 49% in the DCIS to 25% in the IDC component. Despite the genomic similarities between synchronous DCIS and IDC, our data provide strong circumstantial evidence to suggest that in some cases the progression from DCIS to IDC is driven by the selection of non-modal clones that harbour a specific repertoire of genetic aberrations.     

Validity of criteria for establishing maximal O<Subscript>2</Subscript> uptake during ramp exercise tests

The incremental or ramp exercise test to the limit of tolerance has become a popular test for determination of maximal O₂ uptake However, many subjects do not evidence a definitive plateau of the -work rate relationship on this test and secondary criteria based upon respiratory exchange ratio (RER), maximal heart rate (HR_max) or blood [lactate] have been adopted to provide confidence in the measured We hypothesized that verification of using these variables is fundamentally flawed in that their use could either allow underestimation of (if, for any reason, a test were ended at a sub-maximal ), or alternatively preclude subjects from recording a valid Eight healthy male subjects completed a ramp exercise test (at 20 W/min) to the limit of tolerance on an electrically braked cycle ergometer during which pulmonary gas exchange was measured breath-by-breath and blood [lactate] was determined every 90 s. Using the most widely used criterion values of RER (1.10 and 1.15), as determined during the ramp test (4.03 ± 0.10 l/min) could be undermeasured by 27% (2.97 ± 0.24 l/min) and 16% (3.41 ± 0.15 l/min), respectively (both P < 0.05). The criteria of HR_max (age predicted HR_max ± 10 b/min) and blood [lactate] (≥8 mM) were untenable because they resulted in rejection of 3/8 and 6/8 of the subjects, most of whom (5/8) had demonstrated a plateau of at These findings provide a clear mandate for rejecting these secondary criteria as a means of validating on ramp exercise tests.     

\dot{V}_{{{\text{O}}_{2} { \max }}} is not altered by self-pacing during incremental exercise

We tested the hypothesis that incremental cycling to exhaustion that is paced using clamps of the rating of perceived exertion (RPE) elicits higher $ \dot{V}_{{{\text{O}}_{2} { \max }}} $ values compared to a conventional ramp incremental protocol when test duration is matched. Seven males completed three incremental tests to exhaustion to measure $ \dot{V}_{{{\text{O}}_{2} { \max }}} $ . The incremental protocols were of similar duration and included: a ramp test at 30 W min^?1 with constant cadence (RAMP1); a ramp test at 30 W min^?1 with cadence free to fluctuate according to subject preference (RAMP2); and a self-paced incremental test in which the power output was selected by the subject according to prescribed increments in RPE (SPT). The subjects also completed a $ \dot{V}_{{{\text{O}}_{2} { \max }}} $ ‘verification’ test at a fixed high-intensity power output and a 3-min all-out test. No difference was found for $ \dot{V}_{{{\text{O}}_{2} { \max }}} $ between the incremental protocols (RAMP1 = 4.33 ± 0.60 L min^?1; RAMP2 = 4.31 ± 0.62 L min^?1; SPT = 4.36 ± 0.59 L min^?1; P > 0.05) nor between the incremental protocols and the peak $ \dot{V}_{{{\text{O}}_{2} }} $ measured during the 3-min all-out test (4.33 ± 0.68 L min^?1) or the $ \dot{V}_{{{\text{O}}_{2} { \max }}} $ measured in the verification test (4.32 ± 0.69 L min^?1). The integrated electromyogram, blood lactate concentration, heart rate and minute ventilation at exhaustion were not different (P > 0.05) between the incremental protocols. In conclusion, when test duration is matched, SPT does not elicit a higher $ \dot{V}_{{{\text{O}}_{2} { \max }}} $ compared to conventional incremental protocols. The striking similarity of $ \dot{V}_{{{\text{O}}_{2} { \max }}} $ measured across an array of exercise protocols indicates that there are physiological limits to the attainment of $ \dot{V}_{{{\text{O}}_{2} { \max }}} $ that cannot be exceeded by self-pacing.     

微载体培养MEK和Vero细胞试制甲肝灭活疫苗

目的探索微载体培养细胞大量制备甲肝病毒抗原及其灭活疫苗的可行性。方法使用 Cytodex- 1培养恒河猴胚肾细胞和 Vero细胞制备 HAV ,经过初步纯化、甲醛灭活、吸附佐剂 ,制成甲肝灭活疫苗 ,免疫昆明种小白鼠 ,测定免疫原性。结果 HAV X株和 W株抗原滴度分别为 1∶ 2 5 6、1∶ 12 8,感染滴度 (log TCID5 0 / m l)分别为 8.5 0、8.17,与静止培养获得的滴度相当。小鼠抗 HAV抗体第 45 d达到峰值 ,滴度分别为 1∶ (96 .0± 78.4)、1∶ (12 8.0± 70 .1)。结论实验性甲肝灭活疫苗具有良好的免疫原性 ,应用微载体培养细胞制备甲肝灭活疫苗是可行的。     

Profile of denials of durable medical equipment for SCI patients by third party payers

The difficulty in obtaining approval for payment of durable medical equipment by third party payers has impeded the rehabilitation program and discharge planning of many spinal cord patients throughout the country for many years. To gain some insight as to the number and level of patients affected, the kinds of equipment denied, the reasons given for the denial, which third party payers were mostly involved and how the patient and his/her family managed to cope or resolve this problem, a survey was undertaken. Letters were sent to 259 members of the American Spinal Injury Association (ASIA) asking them to list representative cases where requests for equipment deemed necessary were denied. Twenty-eight responses from different institutions were received from sixteen states describing 110 patients and 180 pieces of durable medical equipment denied in 1984 and 1985. Manual wheelchairs, motorized wheelchairs, shower/commode chairs, and environmental control units were the four most common equipment items denied by the third party payers. Government agencies ie., Medicaid, Medicare, Vocational Rehabilitation Departments and State Crippled Children's Services were the most frequent deniers, comprising 54% of the total sample. They were followed by private insurance (31%) and Workman's Compensation (3%). By far, the two most common reasons given for denials were: it was not covered by the insurance policy (38%) and it was not medically necessary (30%). Ninety (90) pieces of equipment (50%) were eventually obtained, most often by charity, or through the patient's family resources.