The frequencies of cells containing mature phages, the burst sizes, the phage head sizes and the distribution of phages inside cells of different bacterial morphotypes were investigated in the ...northern Adriatic Sea. Coccoid bacteria more frequently (2.5%) contained mature phages than rodshaped bacteria (1.2%) and spirillae (1.4%). Including an estimation of non-visible infection we found that up to 27 % of rods were infected with viruses, up to 79 % of cocci and up to 100 % of spirillae. The highest overall infection frequency of the entire bacterial community was 30 %. The percentage of rods with mature phages was significantly correlated to increasing rod densities. It is suggested that a threshold density of about 2 × 105 rods ml−1 exists that is necessary for infection with phages. No threshold densities could be determined for cocci and spirillae. Burst sizes varied strongly between different host morphotypes. The burst sizes of rods increased significantly with the frequency of rods containing mature phages, probably as a result of superinfection of bacteria with phages. The volume of the host cells seemed to influence the number of phages produced per cell. Most of the phages within rods and all phages within spirillae were smaller than 60 nm, whereas the majority of phages within cocci were larger than 60 nm. Analyses of the distribution of phages inside the cells showed that phages were frequently concentrated in 2 defined areas at the 2 opposite ends of both rods and spirillae. Our results from an in situ study suggest that the production of bacteriophages is strongly influenced by the structure of the bacterial community, i.e. by the relative abundances of the various morphotypes.
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In a randomized trial, 2287 patients with coronary artery disease and evidence of ischemia were assigned to receive optimal medical therapy with or without percutaneous coronary intervention (PCI). ...At a median of 4.6 years, the rates of death and myocardial infarction were 19.0% in the PCI group and 18.5% in the medical-therapy group. The PCI group had lower rates of angina and repeat revascularization.
Patients with coronary artery disease and evidence of ischemia were assigned to receive optimal medical therapy with or without percutaneous coronary intervention (PCI). At a median of 4.6 years, the rates of death and myocardial infarction were 19.0% in the PCI group and 18.5% in the medical-therapy group.
During the past 30 years, the use of percutaneous coronary intervention (PCI) has become common in the initial management strategy for patients with stable coronary artery disease in North America, even though treatment guidelines advocate an initial approach with intensive medical therapy, a reduction of risk factors, and lifestyle intervention (known as optimal medical therapy).
1
,
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In 2004, more than 1 million coronary stent procedures were performed in the United States,
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and recent registry data indicate that approximately 85% of all PCI procedures are undertaken electively in patients with stable coronary artery disease.
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PCI reduces the incidence of death and . . .
We assessed whether trivalent live, cold-adapted influenza virus (CAIV-T) vaccine provides added protection when co-administered with trivalent inactivated influenza virus vaccine (TVV) in patients ...with chronic obstructive pulmonary disease (COPD). Subjects (
N=2215) were randomly assigned to receive either TVV intramuscularly (IM) and CAIV-T intranasally (TC), or TVV and placebo (TP). The vaccines were well-tolerated. Efficacy of TC compared to TP was not statistically significant and was 0.16 for any influenza virus strain (95% confidence limit (CL): −0.22, 0.43), 0.26 for A (H3N2) virus (95% CL: −0.17, 0.53), and −0.05 for type B virus (95% CL: −1.13, 0.48). However, there was a possible advantage for TC over TP in reducing respiratory consequences of an influenza season measured by pulmonary function and symptoms at end of study.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The present contribution constitutes the first comprehensive attempt to (a) record the spatial characteristics of the beaches of the Aegean archipelago (Greece), a critical resource for both the ...local and national economy, and (b) provide a rapid assessment of the impacts of the long-term and episodic sea level rise (SLR) under different scenarios. Spatial information and other attributes (e.g., presence of coastal protection works and backshore development) of the beaches of the 58 largest islands of the archipelago were obtained on the basis of remote-sensed images available on the web. Ranges of SLR-induced beach retreats under different morphological, sedimentological and hydrodynamic forcing, and SLR scenarios were estimated using suitable ensembles of cross-shore (1-D) morphodynamic models. These ranges, combined with empirically derived estimations of wave run-up induced flooding, were then compared with the recorded maximum beach widths to provide ranges of retreat/erosion and flooding at the archipelago scale. The spatial information shows that the Aegean pocket beaches may be particularly vulnerable to mean sea level rise (MSLR) and episodic SLRs due to (i) their narrow widths (about 59 % of the beaches have maximum widths < 20 m), (ii) their limited terrestrial sediment supply, (iii) the substantial coastal development and (iv) the limited existing coastal protection. Modeling results indeed project severe impacts under mean and episodic SLRs, which by 2100 could be devastating. For example, under MSLR of 0.5 m – representative concentration pathway (RCP) 4.5 of the Fifth Assessment Report (AR5) of the Intergovernmental Panel on Climate change (IPCC) – a storm-induced sea level rise of 0.6 m is projected to result in a complete erosion of between 31 and 88 % of all beaches (29–87 % of beaches are currently fronting coastal infrastructure and assets), at least temporarily. Our results suggest a very considerable risk which will require significant effort, financial resources and policies/regulation in order to protect/maintain the critical economic resource of the Aegean archipelago.
IMPORTANCE: Serious mental illnesses, including schizophrenia, bipolar disorder, and depression, are heritable, highly multifactorial disorders and major causes of disability worldwide. OBJECTIVE: To ...benchmark the penetrance of current neuropsychiatric polygenic risk scores (PRSs) in the Veterans Health Administration health care system and to explore associations between PRS and broad categories of human disease via phenome-wide association studies. DESIGN, SETTING, AND PARTICIPANTS: Extensive Veterans Health Administration’s electronic health records were assessed from October 1999 to January 2021, and an embedded cohort of 9378 individuals with confirmed diagnoses of schizophrenia or bipolar 1 disorder were found. The performance of schizophrenia, bipolar disorder, and major depression PRSs were compared in participants of African or European ancestry in the Million Veteran Program (approximately 400 000 individuals), and associations between PRSs and 1650 disease categories based on ICD-9/10 billing codes were explored. Last, genomic structural equation modeling was applied to derive novel PRSs indexing common and disorder-specific genetic factors. Analysis took place from January 2021 to January 2022. MAIN OUTCOMES AND MEASURES: Diagnoses based on in-person structured clinical interviews were compared with ICD-9/10 billing codes. PRSs were constructed using summary statistics from genome-wide association studies of schizophrenia, bipolar disorder, and major depression. RESULTS: Of 707 299 enrolled study participants, 459 667 were genotyped at the time of writing; 84 806 were of broadly African ancestry (mean SD age, 58 12.1 years) and 314 909 were of broadly European ancestry (mean SD age, 66.4 13.5 years). Among 9378 individuals with confirmed diagnoses of schizophrenia or bipolar 1 disorder, 8962 (95.6%) were correctly identified using ICD-9/10 codes (2 or more). Among those of European ancestry, PRSs were robustly associated with having received a diagnosis of schizophrenia (odds ratio OR, 1.81 95% CI, 1.76-1.87; P < 10−257) or bipolar disorder (OR, 1.42 95% CI, 1.39-1.44; P < 10−295). Corresponding effect sizes in participants of African ancestry were considerably smaller for schizophrenia (OR, 1.35 95% CI, 1.29-1.42; P < 10−38) and bipolar disorder (OR, 1.16 95% CI, 1.11-1.12; P < 10−10). Neuropsychiatric PRSs were associated with increased risk for a range of psychiatric and physical health problems. CONCLUSIONS AND RELEVANCE: Using diagnoses confirmed by in-person structured clinical interviews and current neuropsychiatric PRSs, the validity of an electronic health records–based phenotyping approach in US veterans was demonstrated, highlighting the potential of PRSs for disentangling biological and mediated pleiotropy.
The depth-dependent, seasonal, and diel variability of virus numbers, dissolved DNA (D-DNA), and other microbial parameters was investigated in the northern Adriatic Sea. During periods of water ...stratification, we found higher virus abundances and virus/bacterium ratios (VBRs) as well as a larger variability of D-DNA concentrations at the thermocline, probably as a result of higher microbial biomass. At the two investigated stations, virus densities were highest in summer and autumn (up to 9.5 ×$10^{10}\ 1^{-1}$) and lowest in winter (<$10^{9}\ 1^{-1}$); D-DNA concentrations were highest in summer and lowest in winter. The VBR as well as an estimated proportion of viral DNA on total D-DNA showed a strong seasonal variability. VBR averaged 15.0 (range, 0.9-89.1), and the percentage of viral DNA in total D-DNA averaged 18.3% (range, 0.1-96.1%). An estimation of the percentage of bacteria lysed by viruses, based on 2-h sample intervals in situ, ranged from 39.6 to 212.2% d-1in 5 m and from 19.9 to 157.2% d-1in 22 m. The estimated contribution of virus-mediated bacterial DNA release to the D-DNA pool ranged from 32.9 to 161% d-1in 5 m and from 10.3 to 74.2% d-1in 22 m. Multiple regression analysis and the diel dynamics of microbial parameters indicate that viral lysis occasionally could be more important in regulating bacterial abundances than grazing by heterotrophic nanoflagellates.
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We conducted a multicenter randomized, double-blind, placebo-controlled trial of early short-term, high-dose methylprednisolone sodium succinate in 223 patients with clinical signs of systemic sepsis ...and a normal sensorium (112 received glucocorticoid and 111 placebo). Patients also received antibiotics and intravenous fluids. Glucocorticoid or placebo was administered intravenously by a bolus (30 mg per kilogram of body weight over 15 minutes) followed by infusion of 5 mg per kilogram per hour for nine hours. The average time between the diagnosis of sepsis and infusion was 2.8 hours. The principal end point was 14-day mortality, which was similar in the placebo (22 percent) and glucocorticoid (21 percent) groups (P = 0.97). Mortality was also not significantly different between those receiving placebo and those receiving glucocorticoid in subgroups with evidence of sepsis (21 vs. 19 percent), gram-negative bacteremia (27 vs. 7 percent), gram-positive bacteremia (18 vs. 26 percent), or all gram-negative infections (25 vs. 17 percent). Resolution of secondary infection within 14 days was significantly higher in patients receiving placebo (12 of 23) than in those receiving glucocorticoid (3 of 16) (P = 0.03), but mortality rates were similar in both treatment groups for those with unresolved infection (36 vs. 31 percent). We conclude that early high-dose glucocorticoid therapy does not reduce mortality significantly in patients with systemic sepsis who have a normal sensorium, and therefore should not be used as adjunctive therapy.
The objective of the study was to determine the microbiological and hygienic quality of milk of Bionda dell'Adamello goats. Forty-three samples of bulk untreated goats' milk and 42 milk-filter ...samples, obtained from six farms, were analysed. The results showed the absence of Listeria spp. in all the milk and milk-filter samples. Considerable differences were observed in terms of milk hygiene (related to total coliforms, E. coli and plate count at 30°C) as the microbiological quality of the milk from only half (3/6) of the farms resulted satisfactory. This finding provides that the ideal way of using the milk of Bionda dell'Adamello goats is producing cheese matured for more than 60 days, as the typical cheese Fatulì.
IMPORTANCE: Many psychiatric outcomes share a common etiologic pathway reflecting behavioral disinhibition, generally referred to as externalizing (EXT) disorders. Recent genome-wide association ...studies (GWASs) have demonstrated the overlap between EXT disorders and important aspects of veterans’ health, such as suicide-related behaviors and substance use disorders (SUDs). OBJECTIVE: To explore correlates of risk for EXT disorders within the Veterans Health Administration (VA) Million Veteran Program (MVP). DESIGN, SETTING, AND PARTICIPANTS: A series of phenome-wide association studies (PheWASs) of polygenic risk scores (PGSs) for EXT disorders was conducted using electronic health records. First, ancestry-specific PheWASs of EXT PGSs were conducted in the African, European, and Hispanic or Latin American ancestries. Next, a conditional PheWAS, covarying for PGSs of comorbid psychiatric problems (depression, schizophrenia, and suicide attempt; European ancestries only), was performed. Lastly, to adjust for unmeasured confounders, a within-family analysis of significant associations from the main PheWAS was performed in full siblings (European ancestries only). This study included the electronic health record data from US veterans from VA health care centers enrolled in MVP. Analyses took place from February 2022 to August 2023 covering a period from October 1999 to January 2020. EXPOSURES: PGSs for EXT, depression, schizophrenia, and suicide attempt. MAIN OUTCOME(S) AND MEASURE(S): Phecodes for diagnoses derived from the International Statistical Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification, codes from electronic health records. RESULTS: Within the MVP (560 824 patients; mean SD age, 67.9 14.3 years; 512 593 male 91.4%), the EXT PGS was associated with 619 outcomes, of which 188 were independent of risk for comorbid problems or PGSs (from odds ratio OR, 1.02; 95% CI, 1.01-1.03 for overweight/obesity to OR, 1.44; 95% CI, 1.42-1.47 for viral hepatitis C). Of the significant outcomes, 73 (11.9%) were significant in the African results and 26 (4.5%) were significant in the Hispanic or Latin American results. Within-family analyses uncovered robust associations between EXT PGS and consequences of SUDs, including liver disease, chronic airway obstruction, and viral hepatitis C. CONCLUSIONS AND RELEVANCE: Results of this cohort study suggest a shared polygenic basis of EXT disorders, independent of risk for other psychiatric problems. In addition, this study found associations between EXT PGS and diagnoses related to SUDs and their sequelae. Overall, this study highlighted the potential negative consequences of EXT disorders for health and functioning in the US veteran population.
We performed a Monte Carlo study to evaluate the effect of the number of events per variable (EPV) analyzed in logistic regression analysis. The simulations were based on data from a cardiac trial of ...673 patients in which 252 deaths occurred and seven variables were cogent predictors of mortality; the number of events per predictive variable was (
252
7
= 36
) for the full sample. For the simulations, at values of EPV = 2, 5, 10, 15, 20, and 25, we randomly generated 500 samples of the 673 patients, chosen with replacement, according to a logistic model derived from the full sample. Simulation results for the regression coefficients for each variable in each group of 500 samples were compared for bias, precision, and significance testing against the results of the model fitted to the original sample.
For EPV values of 10 or greater, no major problems occurred. For EPV values less than 10, however, the regression coefficients were biased in both positive and negative directions; the large sample variance estimates from the logistic model both overestimated and underestimated the sample variance of the regression coeffi-cients; the 90% confidence limits about the estimated values did not have proper coverage; the Wald statistic was conservative under the null hypothesis; and paradoxical associations (significance in the wrong direction) were increased. Although other factors (such as the total number of events, or sample size) may influence the validity of the logistic model, our findings indicate that low EPV can lead to major problems.
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IJS, IMTLJ, KILJ, KISLJ, NUK, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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