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At least 433 records · Page 24Linked to original sources
PubMed2017

Reanalysis of BRCA1/2 negative high risk ovarian cancer patients reveals novel germline risk loci and insights into missing heritability.

While up to 25% of ovarian cancer (OVCA) cases are thought to be due to inherited factors, the majority of genetic risk remains unexplained. To address this gap, we sought to identify previously undescribed OVCA risk variants through the whole exome sequencing (WES) and candidate gene analysis of 48 women with ovarian cancer and selected for high risk of genetic inheritance, yet negative for any known pathogenic variants in either BRCA1 or BRCA2. In silico SNP analysis was employed to identify suspect variants followed by validation using Sanger DNA sequencing. We identified five pathogenic variants in our sample, four of which are in two genes featured on current multi-gene panels; (RAD51D, ATM). In addition, we found a pathogenic FANCM variant (R1931*) which has been recently implicated in familial breast cancer risk. Numerous rare and predicted to be damaging variants of unknown significance were detected in genes on current commercial testing panels, most prominently in ATM (n = 6) and PALB2 (n = 5). The BRCA2 variant p.K3326*, resulting in a 93 amino acid truncation, was overrepresented in our sample (odds ratio = 4.95, p = 0.01) and coexisted in the germline of these women with other deleterious variants, suggesting a possible role as a modifier of genetic penetrance. Furthermore, we detected loss of function variants in non-panel genes involved in OVCA relevant pathways; DNA repair and cell cycle control, including CHEK1, TP53I3, REC8, HMMR, RAD52, RAD1, POLK, POLQ, and MCM4. In summary, our study implicates novel risk loci as well as highlights the clinical utility for retesting BRCA1/2 negative OVCA patients by genomic sequencing and analysis of genes in relevant pathways.

Adult↗
PubMed1994

Reanalysis of the 12-minute walk in patients with chronic obstructive pulmonary disease.

The purpose of this study was to determine the correlation between different intervals in the 12-min walk test, to determine which of the intervals best correlated with maximal oxygen intake (VO2max) and maximal CO2 expelled (VCO2max) and to determine the degree of correlation between changes in the VO2max and changes in the walk test and spirometry. Nine elderly (age, 67 +/- 4 years) patients with moderate COPD (FEV1, 1.32 +/- 0.28 L) who were ventilatory limited were seen 6 times over a 14-week period. At each visit they performed spirometry, a 12-min walk, and a symptom-limited maximal exercise test. During the 12-min walk the distances traversed in each 2-min interval were recorded. A Borg score was obtained at the end of each 2 min. The distances that the patients walked in each 2-min interval were very similar, but the mean Borg score became higher the longer the patient walked. The Borg score after 2 min was 1.64 +/- 1.15, while the Borg score after 12 min was 5.70 +/- 3.59. The correlation coefficients between the distance walked at various intervals and the oxygen consumption (VO2)/kg (approximately 0.65) and the VCO2/kg (approximately 0.52) were very similar. However, changes in the VO2/kg were more closely correlated with changes in the 12-min walk (r = 0.72), than with changes in the 6-min walk (r = 0.64), the 4-min walk (r = 0.59), or the 2-min walk (r = 0.53). This latter observation suggests that the 12-min walk may be preferable to tests in which the patient walks 4 or 6 min for documenting changes in the exercise capabilities.

Aged↗
PubMed2004

Reanalysis of P2X7 receptor expression in rodent brain.

P2X receptors are cationic-selective ion channels gated by extracellular ATP. There are seven subunits (P2X1-7), the first six of which are expressed throughout the peripheral and central nervous systems. P2X7 receptors are rapidly upregulated and activated as a result of inflammatory stimuli in immune cells, where they act not only as cationic channels but uniquely couple with rapid release of proinflammatory cytokines, cytoskeletal rearrangements, and apoptosis or necrotic cell death. The P2X7 receptor has been termed the cytolytic non-neuronal P2X receptor because it had not been detected in neurons until recently when it has been immunolocalized to several brain regions, particularly the hippocampus, and has been suggested to be involved in presynaptic modulation of transmitter release. Because its expression in brain neurons may have substantial functional implications, we have performed detailed immunocytochemical, immunoblot, and immunoprecipitation studies on brain and non-neuronal tissue using all currently available antibodies. We first examined rats, but staining patterns were inconsistent among antibodies; we therefore studied mice for which there are two P2X7 knock-out mice constructs available, one expressing the LacZ transgene. We found that P2X7 receptor protein is strongly and reliably detected in the submandibular gland and lung of wild-type mice but not in either of the P2X7-/- mice. However, we failed to find evidence for P2X7 receptor protein in hippocampal neurons or their input-output projections. Either the P2X7 protein in the hippocampus is below the limits of detection by the currently available methods or it is not present.

Animals↗
PubMed2001

Reduction in diastolic blood pressure and cardiovascular mortality in nondiabetic hypertensive patients. A reanalysis of the HOT study.

OBJECTIVE: To use published Hypertension Optimal Treatment (HOT) Study data to evaluate changes in cardiovascular mortality in nondiabetic hypertensive patients according to the degree of reduction in their diastolic blood pressure. METHODS: In the HOT Study, 18,700 patients from various centers were allocated at random to groups having different objectives of for diastolic blood pressure: </=90 (n=6264); </=85 (n=6264); </=80mmHg (n=6262). Felodipine was the basic drug used. Other antihypertensive drugs were administered in a sequential manner, aiming at the objectives of diastolic blood pressure reduction. RESULTS: The group of nondiabetic hypertensive subjects with diastolic pressure</=80mmHg had a cardiovascular mortality ratio of 4.1/1000 patients/year, 35.5% higher than the group with diastolic pressure </=90mmHg (cardiovascular mortality ratio, 3.1/1000 patients/year). In contrast, diabetic patients allocated to the diastolic pressure objective group of </=80mmHg had a 66.7% reduction in cardiovascular mortality (3.7/1000 patients/year) when compared with the diastolic pressure group of </=90mmHg (cardiovascular mortality ratio, 11.1/1000 patients/year). CONCLUSION: The results indicate that in hypertensive diabetic patients reduction in diastolic blood pressure to levels </=80mmHg decreases the risk of fatal cardiovascular events. It remains necessary to define the level of diastolic blood pressure </=90mmHg at which maximal reduction in cardiovascular mortality is obtained for nondiabetics.

Aged↗
PubMed2001

Statistical reanalysis of the distinction between Spirocamallanus istiblenni and S. monotaxis (Nematoda: Camallanidae).

In the central Pacific, the nematodes Spirocamallanus istiblenni and S. monotaxis (Camallanidae) are common intestinal parasites of coral reef fishes. The 2 worm species are encountered in hosts in similar environments and are very similar morphologically. In recent published redescriptions. only 1 character was found to differ between the 2 species. Because that character had not previously been examined among worms of this family and because the original authors did not statistically test their results, the morphological data are here statistically reexamined for consistency with the differentiation between the 2 species. Both a discriminant function analysis and a hierarchical cluster analysis support the existing species designations based on morphological data. These analyses reaffirmed the conclusions of previous studies; i.e., the relative position of the male's second preanal papilla is the only diagnostic characteristic.

Animals↗
PubMed2001

Relative contribution of residual renal function and peritoneal clearance to adequacy of dialysis: a reanalysis of the CANUSA study.

Studies of the adequacy of peritoneal dialysis and recommendations have assumed that renal and peritoneal clearances are comparable and therefore additive. The CANUSA data were reanalyzed in an effort to address this assumption. Among the 680 patients in the original CANUSA study, 601 had all of the variables of interest for this report. Adequacy of dialysis was estimated from GFR (mean of renal urea and creatinine clearance) and from peritoneal creatinine clearance. The Cox proportional-hazards model was used to evaluate the time-dependent association of these independent variables with patient survival. For each 5 L/wk per 1.73 m(2) increment in GFR, there was a 12% decrease in the relative risk (RR) of death (RR, 0.88; 95% confidence interval [CI], 0.83 to 0.94) but no association with peritoneal creatinine clearance (RR, 1.00; 95% CI, 0.90 to 1.10). Estimates of fluid removal (24-h urine volume, net peritoneal ultrafiltration, and total fluid removal) then were added to the Cox model. For a 250-ml increment in urine volume, there was a 36% decrease in the RR of death (RR, 0.64; 95% CI, 0.51 to 0.80). The association of patient survival with GFR disappeared (RR, 0.99; 95% CI, 0.94 to 1.04). However, neither net peritoneal ultrafiltration nor total fluid removal was associated with patient survival. Although these results may be explained partly, statistically, by less variability in peritoneal clearance than in GFR, the latter seems to be physiologically more important than the former. The assumption of equivalence of peritoneal and renal clearances is not supported by these data. Recommendations for adequate peritoneal dialysis need to be reevaluated in light of these observations.

Adult↗
PubMed2006

Did the pre-1980 use of in-stream structures improve streams? A reanalysis of historical data.

In the 1930s, after only three years of scientific investigation at the University of Michigan Institute for Fisheries Research, cheap labor and government-sponsored conservation projects spearheaded by the Civilian Conservation Corps allowed the widespread adoption of in-stream structures throughout the United States. From the 1940s through the 1970s, designs of in-stream structures remained essentially unchanged, and their use continued. Despite a large investment in the construction of in-stream structures over these four decades, very few studies were undertaken to evaluate the impacts of the structures on the channel and its aquatic populations. The studies that were undertaken to evaluate the impact of the structures were often flawed. The use of habitat structures became an "accepted practice," however, and early evaluation studies were used as proof that the structures were beneficial to aquatic organisms. A review of the literature reveals that, despite published claims to the contrary, little evidence of the successful use of in-stream structures to improve fish populations exists prior to 1980. A total of 79 publications were checked, and 215 statistical analyses were performed. Only seven analyses provide evidence for a benefit of structures on fish populations, and five of these analyses are suspect because data were misclassified by the original authors. Many of the changes in population measures reported in early publications appear to result from changes in fishing pressure that often accompanied channel modifications. Modern evaluations of channel-restoration projects must consider the influence of fishing pressure to ensure that efforts to improve fish habitat achieve the benefits intended. My statistical results show that the traditional use of in-stream structures for channel restoration design does not ensure demonstrable benefits for fish communities, and their ability to increase fish populations should not be presumed.

Animals↗
PubMed1978

Multiple schedule component duration: a reanalysis of Shimp and Wheatley (1971) and Todorov (1972).

The tendency for relative response rate to approach matching as multiple schedule component duration decreases has been interpreted as confirming a prediction of Herrnstein's multiple schedule equation. However, the equation predicts that absolute response rate will decrease in both multiple schedule components as component duration decreases. The absolute response-rate data of two studies of component duration do not support this prediction; absolute rate either increased or remained relatively constant.

Journal Article↗
PubMed1989

Nonhuman short-term memory: A quantitative reanalysis of selected findings.

Intense interest in the experimental analysis of nonhuman short-term memory was occasioned by the "cognitive revolution" in the early 1970s. As researchers tested and refined their theoretical models, a sizable empirical literature on the subject rapidly emerged. Generally missing from that literature, however, is an integrated account of the empirical laws of delayed stimulus control. In its absence, cognitive theories have grown increasingly complex and their connection to established principles of learning more remote. The present article reviews a representative segment of the nonhuman memory literature in an effort to identify and tentatively quantify empirical laws that may underlie some of the major findings. Specifically, a delay-reduction principle adapted from the conditioned reinforcement literature and a proposed principle of serial stimulus compounds were evaluated against data from delayed matching to sample, serial probe recognition, differential outcome, directed forgetting, and surprisingness preparations. Although by no means offering a complete description of the data, the proposed analysis organizes an apparently disparate collection of empirical results and suggests several new lines of inquiry into the subject.

Journal Article↗
PubMed2005

Capturing intervention effects over time: reanalysis of a critical time intervention for homeless mentally ill men.

OBJECTIVES: We analyzed whether a method for identifying latent trajectories--latent class growth analysis (LCGA)--was useful for understanding outcomes for individuals subject to an intervention. METHODS: We used LCGA to reanalyze data from a published study of mentally ill homeless men in a critical time intervention (CTI) program. In that study, 96 men leaving a shelter's on-site psychiatric program were randomly assigned to experimental and control groups. The former received CTI services and the latter usual services. Each individual's housing circumstances were observed for 18 months after program initiation. Our outcome measure was monthly homelessness: a person was considered homeless in a month if he was homeless for even 1 night that month. RESULTS: Four latent classes were found among the control group, but just 3 among the experimental group. Control, but not experimental, group individuals showed a small class of chronically homeless men. The size of the never-homeless class was 19 percentage points larger for the experimental than for the control group. J- and inverted-U-shaped patterns were also found among both groups, but with important differences in timing of patterns. CONCLUSIONS: Our results reveal effects not apparent in the original analysis, suggesting that latent class growth models improve intervention evaluation.

Adult↗
PubMed1996

Acculturation and low-birthweight infants among Latino women: a reanalysis of HHANES data with structural equation models.

Previous studies have demonstrated that acculturation is associated with negative birth outcomes among mothers in numerous immigrant populations, including Latinas. This study used structural equation models to reanalyze data employed in the 1989 Scribner and Dwyer study on the effect of acculturation (measured through the Cuellar scale) on mothers' low-birthweight status. Data revealed that language components dominate the effects of acculturation on low-birthweight status. Acculturuation appears to affect low-birthweight status indirectly through smoking and dietary intake but not through parity. Acculturation has a persistent direct effect on low-birthweight status, suggesting that other intervening variables are operant.

Acculturation↗
PubMed1987

A reanalysis of the relation between unionization and workplace safety.

Although in the United States it is generally believed that the presence of a union has little effect on workplace safety and health, there is a paucity of empirical evidence to support this perception. In this study, the author attempts to provide a preliminary quantitative basis on which the union's role in this area could be evaluated. Examination of the health and safety records of 26 industries over a 9-year period revealed that in some years, greater union coverage is associated with fewer serious on-the-job accidents. However, the average number of days lost from work due to injury was found to increase in direct relation to an increase in industry unionization. Implications of these findings are discussed.

Accidents, Occupational↗
PubMed1999

Effects of repeated hypoglycemia on cognitive function: a psychometrically validated reanalysis of the Diabetes Control and Complications Trial data.

OBJECTIVE: To test the conclusion that there is no association between multiple episodes of severe hypoglycemia and cognitive decrements by reanalyzing the data from the Diabetes Control and Complications Trial (DCCT) with psychometrically validated cognitive factors and to conduct a novel analysis of the association between individual differences in baseline cognitive ability and episodes of severe hypoglycemia documented after baseline. RESEARCH DESIGN AND METHODS: The factor structure of cognitive ability in the neuropsychological data from the DCCT study was derived. Four cognitive factors (spatial ability, processing speed, memory, and verbal ability) were extracted. Changes in patients' cognitive scores for each year of follow-up were obtained, and paired comparisons of these change scores were performed between groups experiencing zero and five or more hypoglycemic episodes. The association between cognitive ability at baseline and number of subsequent episodes of severe hypoglycemia was also examined. RESULTS: Repeated episodes of hypoglycemia were found not to be associated with cognitive decline in any of the validated cognitive factors. No significant association was found between prospectively documented numbers of severe hypoglycemic episodes and baseline cognitive ability level. CONCLUSIONS: Repeated episodes of hypoglycemia were not related to cognitive decrement, and initial mental ability level was not associated with eventual numbers of hypoglycemic episodes in this group of patients.

Adolescent↗