Capitalism, politics, and railroads in Prussia, 1830-1870

(print) xi, 273 p. ; 24 cmPreface -- Capital and political authority in German history. p.1 -- Private or state owned? The railroad question, 1830-1848. p.22 -- The search for mutual accommodation, 1848-1857. p.53 -- The conflict over night trains. p.75 -- Banking and the business class. p.87 -- The Railroad Fund, 1842-1859. p.107 -- The juste milieu, 1857-1870. p.135 -- Conclusion. p.165 -- List of abbreviations. p.177 -- Notes. p.179 -- Bibliography. p.247 -- Index. p.26

The potential interaction between clopidogrel and proton pump inhibitors: a systematic review

<p>Abstract</p> <p>Background</p> <p>Recently, several publications have investigated a possible drug interaction between clopidogrel and proton pump inhibitors (PPIs), and regulatory agencies have issued warnings despite discordant study results. In an attempt to clarify the situation, we performed a systematic review with a critical analysis of study methodologies to determine whether varying study quality (that is, bias) could explain the discordant results.</p> <p>Methods</p> <p>A systematic review of all studies reporting clinical outcomes was performed using an electronic literature search of the MEDLINE and EMBASE databases, abstracts from the major cardiology conferences and a hand-search of bibliographies from identified articles. Each study was evaluated for its risk of bias according to a prespecified quality measure scale.</p> <p>Results</p> <p>A total of 18 studies were identified. Ten of 13 studies judged to be of low scientific quality reported a statistically positive interaction between clopidogrel and the general class of PPIs, and each concluded this was likely a clinically meaningful effect. None of the five studies judged to be of moderate or high quality reported a statistically significant association. Multiple sources of heterogeneity (that is, different populations, outcomes assessed, drug exposure methods and study quality) prevented a formal quantitative analysis of all studies. An increased risk of bias was observed in the positive studies, resulting in an inverse correlation between study quality and a reported statistically positive interaction (10/13 versus 0/5; <it>P </it>= p = 0.007). There was also no clinical evidence for a positive interaction according to specific PPIs.</p> <p>Conclusion</p> <p>The observed association between clopidogrel and PPIs is found uniquely in studies judged to be of low quality and with an increased risk of bias. High-quality evidence supporting a clinically significant clopidogrel/PPI interaction is presently lacking.</p

Risk of acute myocardial infarction with NSAIDs in real world use : bayesian meta-analysis of individual patient data

OBJECTIVE To characterise the determinants, time course, and risks of acute myocardial infarction associated with use of oral non-steroidal anti-inflammatory drugs (NSAIDs). DESIGN Systematic review followed by a one stage bayesian individual patient data meta-analysis. DATA SOURCES Studies from Canadian and European healthcare databases. REVIEW METHODS Eligible studies were sourced from computerised drug prescription or medical databases, conducted in the general or an elderly population, documented acute myocardial infarction as specific outcome, studied selective cyclo-oxygenase-2 inhibitors (including rofecoxib) and traditional NSAIDs, compared risk of acute myocardial infarction in NSAID users with non-users, allowed for time dependent analyses, and minimised effects of confounding and misclassification bias. EXPOSURE AND OUTCOMES Drug exposure was modelled as an indicator variable incorporating the specific NSAID, its recency, duration of use, and dose. The outcome measures were the summary adjusted odds ratios of first acute myocardial infarction after study entry for each category of NSAID use at index date (date of acute myocardial infarction for cases, matched date for controls) versus non-use in the preceding year and the posterior probability of acute myocardial infarction. RESULTS A cohort of 446 763 individuals including 61 460 with acute myocardial infarction was acquired. Taking any dose of NSAIDs for one week, one month, or more than a month was associated with an increased risk of myocardial infarction. With use for one to seven days the probability of increased myocardial infarction risk (posterior probability of odds ratio >1.0) was 92% for celecoxib, 97% for ibuprofen, and 99% for diclofenac, naproxen, and rofecoxib. The corresponding odds ratios (95% credible intervals) were 1.24 (0.91 to 1.82) for celecoxib, 1.48 (1.00 to 2.26) for ibuprofen, 1.50 (1.06 to 2.04) for diclofenac, 1.53 (1.07 to 2.33) for naproxen, and 1.58 (1.07 to 2.17) for rofecoxib. Greater risk of myocardial infarction was documented for higher dose of NSAIDs. With use for longer than one month, risks did not appear to exceed those associated with shorter durations. CONCLUSIONS All NSAIDs, including naproxen, were found to be associated with an increased risk of acute myocardial infarction. Risk of myocardial infarction with celecoxib was comparable to that of traditional NSAIDS and was lower than for rofecoxib. Risk was greatest during the first month of NSAID use and with higher doses.Peer reviewe

Towards delineating functions within the fasciola secreted cathepsin L protease family by integrating in vivo based sub-proteomics and phylogenetics

BACKGROUND: Fasciola hepatica, along with Fasciola gigantica, is the causative agent of fasciolosis, a foodborne zoonotic disease affecting grazing animals and humans worldwide. Pathology is directly related to the release of parasite proteins that facilitate establishment within the host. The dominant components of these excretory-secretory (ES) products are also the most promising vaccine candidates, the cathepsin L (Cat L) protease family. METHODOLOGY/PRINCIPAL FINDINGS: The sub-proteome of Cat L proteases from adult F. hepatica ES products derived from in vitro culture and in vivo from ovine host bile were compared by 2-DE. The individual Cat L proteases were identified by tandem mass spectrometry with the support of an in-house translated liver fluke EST database. The study reveals plasticity within the CL1 clade of Cat L proteases; highlighted by the identification of a novel isoform and CL1 sub-clade, resulting in a new Cat L phylogenetic analysis including representatives from other adult Cat L phylogenetic clades. Additionally, for the first time, mass spectrometry was shown to be sufficiently sensitive to reveal single amino acid polymorphisms in a resolved 2-DE protein spot derived from pooled population samples. CONCLUSIONS/SIGNIFICANCE: We have investigated the sub-proteome at the population level of a vaccine target family using the Cat L proteases from F. hepatica as a case study. We have confirmed that F. hepatica exhibits more plasticity in the expression of the secreted CL1 clade of Cat L proteases at the protein level than previously realised. We recommend that superfamily based vaccine discovery programmes should screen parasite populations from different host populations and, if required, different host species via sub-proteomic assay in order to confirm the relative expression at the protein level prior to the vaccine development phase

Sex Ratio Changes as Sentinel Health Events of Endocrine Disruption

The production and widespread use of synthetic chemicals since the 1940s have resulted in ubiquitous contamination of fish, wildlife and human populations. Since the 1960s, observers have documented major damage to wildlife reproduction across the globe, and subsequently, damage to reproductive health in exposed humans as well. The sex ratio in human communities and populations can be readily measured to ascertain whether reproductive effects, such as subtle birth defects of the reproductive tract caused by exposures to chemicals, might be occurring. Male to femalesex ratios appear to be declining in populations in several parts of the globe, possibly as a result of prenatal exposures to chemicals. Sex ratio data for communitieswith unusual occupational or environmental exposures can be compiled using traditional epidemiological techniques in pursuit of environmental justice. Local, regional and national population health researchers and occupational hygienists can use health statistics toexamine sex ratios as sentinel health events that might portend patterns of subtle structural birth defects of the reproductive tract and functional deficits in neurodevelopment

Occupational Histories of Cancer Patients in a Canadian Cancer Treatment Centre and the Generated Hypothesis Regarding Breast Cancer and Farming

Occupational exposures increase cancer risks. The Windsor Regional Cancer Centre in Windsor, Ontario, was the first Canadian cancer treatment center to collect the work histories of its patients, which were recorded using a computer-based questionnaire. Breast cancer cases represented the largest respondent group. The lifetime occupational histories of 299 women with newly diagnosed breast cancers were compared with those of 237 women with other cancers. Odds ratios (ORs) were calculated using logistic regression, adjusting for age, social class, and education. The OR for women £ 55 years of age with breast cancer who had ever farmed, compared with women of the same age with other cancers, was 9.05 (95% CI 1.06, 77.43). Patients’ occupational histories can help to inform understanding of cancer etiology and prevention. This effort points to a need for investigation of the possible association between breast cancer and agricultural hazards such as pesticides

Experimental Evaluation of Russian Anode Layer Thrusters

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76973/1/AIAA-1994-3010-800.pd

Sacrificed: Ontario Healthcare Workers in the Time of COVID-19

Healthcare workers (HCWs) in Ontario, Canada have faced unprecedented risks during the COVID-19 pandemic. They have been infected at an elevated rate compared to the general public. HCWs have argued for better protections with minimal success. A worldwide shortage of N95s and comparable respirators appears to have influenced guidelines for protection, which stand at odds with increasing scientific evidence. In-depth interviews were conducted with ten frontline HCWs about their concerns. They reported that the risk of contracting COVID-19 and infecting family members has created intense anxiety. This, in conjunction with understaffing and an increased workload, has resulted in exhaustion and burnout. HCWs feel abandoned by their governments, which failed to prepare for an inevitable epidemic, despite recommendations. The knowledge that they are at increased risk of infection due to lack of protection has resulted in anger, frustration, fear, and a sense of violation that may have long-lasting implications

Outcomes after angiography with sodium bicarbonate and acetylcysteine

Background: Intravenous sodium bicarbonate and oral acetylcysteine are widely used to prevent acute kidney injury and associated adverse outcomes after angiography without definitive evidence of their efficacy. Methods: Using a 2-by-2 factorial design, we randomly assigned 5177 patients at high risk for renal complications who were scheduled for angiography to receive intravenous 1.26% sodium bicarbonate or intravenous 0.9% sodium chloride and 5 days of oral acetylcysteine or oral placebo; of these patients, 4993 were included in the modified intention-to-treat analysis. The primary end point was a composite of death, the need for dialysis, or a persistent increase of at least 50% from baseline in the serum creatinine level at 90 days. Contrast-associated acute kidney injury was a secondary end point. Results: The sponsor stopped the trial after a prespecified interim analysis. There was no interaction between sodium bicarbonate and acetylcysteine with respect to the primary end point (P=0.33). The primary end point occurred in 110 of 2511 patients (4.4%) in the sodium bicarbonate group as compared with 116 of 2482 (4.7%) in the sodium chloride group (odds ratio, 0.93; 95% confidence interval [CI], 0.72 to 1.22; P=0.62) and in 114 of 2495 patients (4.6%) in the acetylcysteine group as compared with 112 of 2498 (4.5%) in the placebo group (odds ratio, 1.02; 95% CI, 0.78 to 1.33; P=0.88). There were no significant between-group differences in the rates of contrast-associated acute kidney injury. Conclusions: Among patients at high risk for renal complications who were undergoing angiography, there was no benefit of intravenous sodium bicarbonate over intravenous sodium chloride or of oral acetylcysteine over placebo for the prevention of death, need for dialysis, or persistent decline in kidney function at 90 days or for the prevention of contrast-associated acute kidney injury. (Funded by the U.S. Department of Veterans Affairs Office of Research and Development and the National Health and Medical Research Council of Australia; PRESERVE ClinicalTrials.gov number, NCT01467466.