Community-Based Outbreaks in Vulnerable Populations of Invasive Infections Caused by Streptococcus pneumoniae Serotypes 5 and 8 in Calgary, Canada

BACKGROUND: Outbreaks of invasive pneumococcal disease (IPD) typically occur within institutions. Beginning in 2005, we detected an increase in serotype (ST) 5 and ST8 IPD cases, predominantly in homeless persons living in an open community. METHODOLOGY/PRINCIPAL FINDINGS: CASPER (Calgary Area S. pneumoniae Epidemiology Research) surveillance study of all IPD (sterile site isolates) in our region (pop ~1,100,000). Interviews and chart reviews of all cases and all isolates phenotypically analyzed and selected isolated tested by multi-locus sequence typing (MLST). CONCLUSIONS/SIGNIFICANCE: During 2005-2007, 162 cases of ST5 IPD and 45 cases of ST8 IPD were identified. The isolates demonstrated phenotypic and genotypic clonality. The ST5 isolates were sequence type (ST) 289 and demonstrated intermediate susceptibility to TMP-SMX. The ST8 isolates were predominantly ST1268, with a susceptible antimicrobial susceptibility profile. Individuals with ST5 IPD were more likely to be middle aged (OR 2.6), homeless (OR 4.4), using illicit drugs(OR 4.8), and asthmatic(OR 2.6). Those with ST8 were more likely to be male (OR 4.4), homeless (OR 2.6), aboriginal (OR7.3), and a current smoker (OR 2.5). Overlapping outbreaks of ST5 and ST8 IPD occurred in an open community in Calgary, Canada and homelessness was a predominant risk factor. Homelessness represents a unique community in which pneumococcal outbreaks can occur

Application of the speed-duration relationship to normalize the intensity of high-intensity interval training

The tolerable duration of continuous high-intensity exercise is determined by the hyperbolic Speed-tolerable duration (S-tLIM) relationship. However, application of the S-tLIM relationship to normalize the intensity of High-Intensity Interval Training (HIIT) has yet to be considered, with this the aim of present study. Subjects completed a ramp-incremental test, and series of 4 constant-speed tests to determine the S-tLIM relationship. A sub-group of subjects (n = 8) then repeated 4 min bouts of exercise at the speeds predicted to induce intolerance at 4 min (WR4), 6 min (WR6) and 8 min (WR8), interspersed with bouts of 4 min recovery, to the point of exercise intolerance (fixed WR HIIT) on different days, with the aim of establishing the work rate that could be sustained for 960 s (i.e. 4×4 min). A sub-group of subjects (n = 6) also completed 4 bouts of exercise interspersed with 4 min recovery, with each bout continued to the point of exercise intolerance (maximal HIIT) to determine the appropriate protocol for maximizing the amount of high-intensity work that can be completed during 4×4 min HIIT. For fixed WR HIIT tLIM of HIIT sessions was 399±81 s for WR4, 892±181 s for WR6 and 1517±346 s for WR8, with total exercise durations all significantly different from each other (P<0.050). For maximal HIIT, there was no difference in tLIM of each of the 4 bouts (Bout 1: 229±27 s; Bout 2: 262±37 s; Bout 3: 235±49 s; Bout 4: 235±53 s; P>0.050). However, there was significantly less high-intensity work completed during bouts 2 (153.5±40. 9 m), 3 (136.9±38.9 m), and 4 (136.7±39.3 m), compared with bout 1 (264.9±58.7 m; P>0.050). These data establish that WR6 provides the appropriate work rate to normalize the intensity of HIIT between subjects. Maximal HIIT provides a protocol which allows the relative contribution of the work rate profile to physiological adaptations to be considered during alternative intensity-matched HIIT protocols

The Effect of Testing on the Retention of Coherent and Incoherent Text Material

Research has shown that testing during learning can enhance the long-term retention of text material. In two experiments, we investigated the testing effect with a fill-in-the-blank test on the retention of text material. In Experiment 1, using a coherent text, we found no retention benefit of testing compared to a restudy (control) condition. In Experiment 2, text coherence was disrupted by scrambling the order of the sentences from the text. The material was subsequently presented as a list of facts as opposed to connected discourse. For the incoherent version of the text, testing slowed down the rate of forgetting compared to a restudy (control) condition. The results suggest that the connectedness of materials can play an important role in determining the magnitude of testing benefits for long-term retention. Testing with a completion test seems most beneficial for unconnected materials and less so for highly structured materials

Recessive nephrocerebellar syndrome on the Galloway-Mowat syndrome spectrum is caused by homozygous protein-truncating mutations of WDR73.

We describe a novel nephrocerebellar syndrome on the Galloway-Mowat syndrome spectrum among 30 children (ages 1.0 to 28 years) from diverse Amish demes. Children with nephrocerebellar syndrome had progressive microcephaly, visual impairment, stagnant psychomotor development, abnormal extrapyramidal movements and nephrosis. Fourteen died between ages 2.7 and 28 years, typically from renal failure. Post-mortem studies revealed (i) micrencephaly without polymicrogyria or heterotopia; (ii) atrophic cerebellar hemispheres with stunted folia, profound granule cell depletion, Bergmann gliosis, and signs of Purkinje cell deafferentation; (iii) selective striatal cholinergic interneuron loss; and (iv) optic atrophy with delamination of the lateral geniculate nuclei. Renal tissue showed focal and segmental glomerulosclerosis and extensive effacement and microvillus transformation of podocyte foot processes. Nephrocerebellar syndrome mapped to 700 kb on chromosome 15, which contained a single novel homozygous frameshift variant (WDR73 c.888delT; p.Phe296Leufs*26). WDR73 protein is expressed in human cerebral cortex, hippocampus, and cultured embryonic kidney cells. It is concentrated at mitotic microtubules and interacts with α-, β-, and γ-tubulin, heat shock proteins 70 and 90 (HSP-70; HSP-90), and the carbamoyl phosphate synthetase 2/aspartate transcarbamylase/dihydroorotase multi-enzyme complex. Recombinant WDR73 p.Phe296Leufs*26 and p.Arg256Profs*18 proteins are truncated, unstable, and show increased interaction with α- and β-tubulin and HSP-70/HSP-90. Fibroblasts from patients homozygous for WDR73 p.Phe296Leufs*26 proliferate poorly in primary culture and senesce early. Our data suggest that in humans, WDR73 interacts with mitotic microtubules to regulate cell cycle progression, proliferation and survival in brain and kidney. We extend the Galloway-Mowat syndrome spectrum with the first description of diencephalic and striatal neuropathology

Management of congestive heart failure: a gender gap may still exist. Observations from a contemporary cohort

BACKGROUND: Unlike other cardiovascular diseases the incidence and prevalence of congestive heart failure (CHF) continues to increase. While gender differences in coronary artery disease have been well described, to date, there has been a relative paucity of similar data in patients with CHF. We conducted a pilot study to evaluate the profile and management of patients with CHF at a tertiary care centre to determine if a gender difference exists. METHODS: A chart review was performed at a tertiary care centre on consecutive patients admitted with a primary diagnosis of CHF between June 1997 and 1998. Co-morbidity, diagnostic investigations, and management of CHF were recorded. Comparisons between male and female patients were conducted. RESULTS: One hundred and forty five patients were reviewed. There were 80 male (M) and 65 female (F) patients of similar age [71.6 vs. 71.3 (M vs. F), p = NS]. Male patients were more likely to have had a previous myocardial infarction (66% vs. 35%, p < 0.01) and revascularization (41% vs. 20%, p < 0.05), and had worse left ventricular ejection fraction (LVEF) than women, [median LVEF 3 vs. 2 (M vs. F), p < 0.01]. Male patients were more likely to have a non-invasive assessment of left ventricular (LV) function [85% vs. 69%, (M vs. F), p < 0.05]. A logistic regression analysis suggests that amongst those without coronary disease, males were more likely to receive non-invasive testing. There were no differences in the use of prescribed medications, in this cohort. CONCLUSIONS: This pilot study demonstrated that there seem to be important gender differences in the profile and management of patients with CHF. Importantly women were less likely to have an evaluation of LV function. As assessment of LV function has significant implications on patient management, this data justifies the need for larger studies to assess gender differences in CHF profile and treatment

‘There is a Time to be Born and a Time to Die’ (Ecclesiastes 3:2a): Jewish Perspectives on Euthanasia

Reviewing the publications of prominent American rabbis who have (extensively) published on Jewish biomedical ethics, this article highlights Orthodox, Conservative and Reform opinions on a most pressing contemporary bioethical issue: euthanasia. Reviewing their opinions against the background of the halachic character of Jewish (biomedical) ethics, this article shows how from one traditional Jewish textual source diverse, even contradictory, opinions emerge through different interpretations. In this way, in the Jewish debate on euthanasia the specific methodology of Jewish (bio)ethical reasoning comes forward as well as a diversity of opinion within Judaism and its branches

Accelerating Policy Decisions to Adopt Haemophilus influenzae Type b Vaccine: A Global, Multivariable Analysis

Jessica Shearer and colleagues analyze data from 147 countries to identify factors that influence the time taken to introduce routine vaccination against Haemophilus influenzae type b (Hib)

Primary and booster vaccination in Latin American children with a DTPw-HBV/Hib combination: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Diphtheria-tetanus-whole-cell pertussis (DTPw)-based combination vaccines are an attractive option to rapidly achieve high coverage and protection against other important pathogens, such as hepatitis B virus (HBV) and <it>Haemophilus influenzae </it>type B (Hib). To ensure adequate antigen supply, GlaxoSmithKline Biologicals has introduced a new DTPw antigen source and developed a new DTPw-HBV/Hib combination vaccine containing a reduced amount of Hib polyribosylribitol phosphate (PRP). This study was undertaken to compare the immunogenicity and reactogenicity of this new DTPw-HBV/Hib vaccine with a licensed DTPw-HBV/Hib vaccine (<it>Tritanrix</it>™-HBV/Hib).</p> <p>Methods</p> <p>This was a randomized, partially-blind, multicenter study in three countries in Latin America (Argentina, Chile and Nicaragua). Healthy children received either the new DTPw-HBV/Hib vaccine (1 of 3 lots; n = 439; double-blind) or Tritanrix™-HBV/Hib (n = 146; single-blind) co-administered with oral poliovirus vaccine (OPV) at 2, 4 and 6 months, with a booster dose at 18-24 months.</p> <p>Results</p> <p>One month after the end of the 3-dose primary vaccination course, the new DTPw-HBV/Hib vaccine was non-inferior to Tritanrix™-HBV/Hib in terms of seroprotection/vaccine response rates for all component antigens; ≥97.3% and ≥93.9% of subjects in the two groups, respectively, had seroprotective levels of antibodies against diphtheria, tetanus, hepatitis B and Hib and a vaccine response to the pertussis component. Persistence of antibodies against all vaccine antigens was comparable between groups, with marked increases in all antibody concentrations after booster administration in both groups. Both vaccines were generally well-tolerated as primary and booster doses.</p> <p>Conclusions</p> <p>Results confirm the suitability of this new DTPw-HBV/Hib vaccine comprising antigens from a new source and a reduced PRP content for inclusion into routine childhood vaccination programs.</p> <p>Trial registration</p> <p><url>http://www.clinicaltrials.gov</url> NCT00332566</p