Alfred Russel Wallace and the Antivaccination Movement in Victorian England

Historical analysis can play a major role in public health policy

Outcomes of Sphincter of Oddi Manometry When Performed in Low Volumes

Background. Sphincter of Oddi manometry is a highly specialized procedure associated with an increased risk of procedural complications. Published studies have typically been performed in large volume manometry centers. Objective. To examine the outcomes and complication rate of SOM when performed in small volumes. Design. Retrospective analysis at a tertiary care referral hospital that infrequently performs Sphincter of Oddi manometry. Patient records were reviewed for procedural details, patient outcomes, and complications after sphincter of Oddi manometry. Results. 36 patients, 23 (23 type II sphincter of Oddi dysfunction (SOD), 13 type III SOD) underwent sphincter of Oddi manometry and were followed up for mean of 16 months. Nine Type II patients (90%) with elevated basal sphincter pressures noted symptom improvement after sphincterotomy compared with only 3 patients (43%) of the patients with normal basal pressures. In type III SOD, 7 patients had elevated basal SO pressure and underwent sphincterotomy. Three patients (43%) improved. There were six (16%) procedure-related complications. There were four cases of post ERCP pancreatitis (11%), all of which were mild. Conclusion. In low numbers, sphincter of Oddi manometry can be performed successfully and safely by experienced biliary endoscopists with results that are comparable to large volume centers

Patent Litigation in Europe

We compare patent litigation cases across four European jurisdictions—Germany, the UK (England and Wales), France, The Netherlands—using case-level data gathered from cases filed in the four jurisdictions during the period 2000–2008. Overall, we find substantial differences across jurisdictions in terms of caseloads—notably, courts in Germany hear by far the largest number of cases, not only in absolute terms, but also when taking macro-economic indicators into account—and we further find important cross-country variances in terms of case outcomes. Moreover, we show empirically that a considerable number of patents are litigated across multiple European jurisdictions; and further, that in the majority of these cases divergent case outcomes are reached across the different jurisdictions, suggesting that the long-suspected problem of inconsistency of decision-making in European patent litigation is in fact real. Finally, we note that the coming into force of the Unified Patent Court in Europe may, in the long term, help to alleviate this inconsistency problem

Longitudinal Analysis of Quality of Life, Clinical, Radiographic, Echocardiographic, and Laboratory Variables in Dogs with Preclinical Myxomatous Mitral Valve Disease Receiving Pimobendan or Placebo: The EPIC Study

Background: Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and cardiomegaly have not been described. Objectives: To investigate the effect of pimobendan on clinical variables and the relationship between a change in heart size and the time to congestive heart failure (CHF) or cardiac-related death (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan-treated dogs differ from dogs receiving placebo at onset of CHF. Animals: Three hundred and fifty-four dogs with MMVD and cardiomegaly. Materials and Methods: Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4-0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart-size variables in both groups were measured and compared at different time points (day 35 and onset of CHF) and over the study duration. Relationships between short-term changes in echocardiographic variables and time to CHF or CRD were explored. Results: At day 35, heart size had reduced in the pimobendan group:median change in (Delta) LVIDDN -0.06 (IQR:-0.15 to + 0.02), P < 0.0001, and LA:Ao -0.08 (IQR:-0.23 to + 0.03), P < 0.0001. Reduction in heart size was associated with increased time to CHF or CRD. Hazard ratio for a 0.1 increase in Delta LVIDDN was 1.26, P = 0.0003. Hazard ratio for a 0.1 increase in Delta LA:Ao was 1.14, P = 0.0002. At onset of CHF, groups were similar. Conclusions and Clinical Importance: Pimobendan treatment reduces heart size. Reduced heart size is associated with improved outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable from those receiving placebo

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study - A Randomized Clinical Trial

Background: Pimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown. Hypothesis/Objectives: Administration of pimobendan (0.4-0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac-related death, or euthanasia. Animals: 360 client-owned dogs with MMVD with left atrial-to-aortic ratio >= 1.6, normalized left ventricular internal diameter in diastole >= 1.7, and vertebral heart sum >10.5. Methods: Prospective, randomized, placebo-controlled, blinded, multicenter clinical trial. Primary outcome variable was time to a composite of the onset of CHF, cardiac-related death, or euthanasia. Results: Median time to primary endpoint was 1228 days (95% CI: 856-NA) in the pimobendan group and 766 days (95% CI: 667-875) in the placebo group (P = .0038). Hazard ratio for the pimobendan group was 0.64 (95% CI: 0.47-0.87) compared with the placebo group. The benefit persisted after adjustment for other variables. Adverse events were not different between treatment groups. Dogs in the pimobendan group lived longer (median survival time was 1059 days (95% CI: 952-NA) in the pimobendan group and 902 days (95% CI: 747-1061) in the placebo group) (P = .012). Conclusions and Clinical Importance: Administration of pimobendan to dogs with MMVD and echocardiographic and radiographic evidence of cardiomegaly results in prolongation of preclinical period and is safe and well tolerated. Prolongation of preclinical period by approximately 15 months represents substantial clinical benefit

Why do only some people who support parties actually join them? Evidence from Britain

What makes people join a political party is one of the most commonly studied questions in research on party members. Nearly all this research, however, is based on talking to people who have actually joined parties. This article simultaneously analyses surveys of members of political parties in Britain and surveys of non-member supporters of those same parties. This uniquely enables us to model the decision to join parties. The results suggest that most of the elements that constitute the influential ‘General Incentives Model’ are significant. But it also reveals that, while party supporters imagine that selective benefits, social norms and opposing rival parties’ policies are key factors in members’ decisions to join a party, those who actually do so are more likely to say they are motivated by attachments to their party’s values, policies and leaders, as well as by an altruistic desire to support democracy more generally

Contracting on litigation

Two risk‐averse litigants with different subjective beliefs negotiate in the shadow of a pending trial. Through contingent contracts, the litigants can mitigate risk and/or speculate on the trial outcome. Contingent contracting decreases the settlement rate and increases the volume and costs of litigation. These contingent contracts mimic the services provided by third‐party investors, including litigation funders and insurance companies. The litigants (weakly) prefer to contract with risk‐neutral third parties when the capital market is transaction‐cost free. However, contracting with third parties further decreases the settlement rate, increases the costs of litigation, and may increase the aggregate cost of risk bearing.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149242/1/rand12274.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149242/2/rand12274_am.pd

Magnetic Fluffy Dark Matter

We explore extensions of inelastic Dark Matter and Magnetic inelastic Dark Matter where the WIMP can scatter to a tower of heavier states. We assume a WIMP mass $m_\chi \sim \mathcal{O}(1-100)$ GeV and a constant splitting between successive states $\delta \sim\mathcal{O}(1 - 100)$ keV. For the spin-independent scattering scenario we find that the direct experiments CDMS and XENON strongly constrain most of the DAMA/LIBRA preferred parameter space, while for WIMPs that interact with nuclei via their magnetic moment a region of parameter space corresponding to $m_{\chi}\sim 11$ GeV and $\delta < 15$ keV is allowed by all the present direct detection constraints.Comment: 16 pages, 6 figures, added comments about magnetic moment form factor to Sec 3.1.2 and results to Sec 3.2.2, final version to be published in JHE

Low-level APC mutational mosaicism is the underlying cause in a substantial fraction of unexplained colorectal adenomatous polyposis cases

BACKGROUND: In 30-50% of patients with colorectal adenomatous polyposis, no germline mutation in the known genes APC, causing familial adenomatous polyposis, MUTYH, causing MUTYH-associated polyposis, or POLE or POLD1, causing polymerase-proofreading-associated polyposis can be identified, although a hereditary aetiology is likely. This study aimed to explore the impact of APC mutational mosaicism in unexplained polyposis. METHODS: To comprehensively screen for somatic low-level APC mosaicism, high-coverage next-generation sequencing of the APC gene was performed using DNA from leucocytes and a total of 53 colorectal tumours from 20 unrelated patients with unexplained sporadic adenomatous polyposis. APC mosaicism was assumed if the same loss-of-function APC mutation was present in ≥2 anatomically separated colorectal adenomas/carcinomas per patient. All mutations were validated using diverse methods. RESULTS: In 25% (5/20) of patients, somatic mosaicism of a pathogenic APC mutation was identified as underlying cause of the disease. In 2/5 cases, the mosaic level in leucocyte DNA was slightly below the sensitivity threshold of Sanger sequencing; while in 3/5 cases, the allelic fraction was either very low (0.1-1%) or no mutations were detectable. The majority of mosaic mutations were located outside the somatic mutation cluster region of the gene. CONCLUSIONS: The present data indicate a high prevalence of pathogenic mosaic APC mutations below the detection thresholds of routine diagnostics in adenomatous polyposis, even if high-coverage sequencing of leucocyte DNA alone is taken into account. This has important implications for both routine work-up and strategies to identify new causative genes in this patient group