The Samoa Hurricane, 15-16 March 1889

Analysing historical weather extremes such as the tropical cyclone in Samoa in March 1889 could add to our understanding of extreme events. However, up to now the availability of suitable data was limiting the analysis of historical extremes, particularly in remote regions. The new “Twentieth Century Reanalysis” (20CR), which provides six-hourly, three-dimensional data for the entire globe back to 1871, might provide the means to study this and other early events. While its suitability for studying historical extremes has been analysed for events in the northern extratropics (see other papers in this volume), the representation of tropical cyclones, especially in early times, remains unknown. The aim of this paper is to study to the hurricane that struck Samoa on 15-16 March 1889. We analyse the event in 20CR as well as in contemporary observations. We find that the event is not reproduced in the ensemble mean of 20CR, nor is it within the ensemble spread. We argue that this is due to the paucity of data assimilated into 20CR. A preliminary compilation of historical observations from ships for that period, in contrast, provides a relatively consistent picture of the event. This shows that more observations would be available and implies that future versions of surface-based reanalyses might profit from digitizing further observations in the tropical region.

Sphingosine 1-phosphate (S1P) induces COX-2 expression and PGE2 formation via S1P receptor 2 in renal mesangial cells

Understanding the mechanisms of sphingosine 1-phosphate (S1P)-induced cyclooxygenase (COX)-2 expression and prostaglandin E2 (PGE2) formation in renal mesangial cells may provide potential therapeutic targets to treat inflammatory glomerular diseases. Thus, we evaluated the S1P-dependent signaling mechanisms which are responsible for enhanced COX-2 expression and PGE2 formation in rat mesangial cells under basal conditions. Furthermore, we investigated whether these mechanisms are operative in the presence of angiotensin II (Ang II) and of the pro-inflammatory cytokine interleukin-1β (IL-1β). Treatment of rat and human mesangial cells with S1P led to concentration-dependent enhanced expression of COX-2. Pharmacological and molecular biology approaches revealed that the S1P-dependent increase of COX-2 mRNA and protein expression was mediated via activation of S1P receptor 2 (S1P2). Further, inhibition of Gi and p42/p44 MAPK signaling, both downstream of S1P2, abolished the S1P-induced COX-2 expression. In addition, S1P/S1P2-dependent upregulation of COX-2 led to significantly elevated PGE2 levels, which were further potentiated in the presence of Ang II and IL-1β. A functional consequence downstream of S1P/S1P2 signaling is mesangial cell migration that is stimulated by S1P. Interestingly, inhibition of COX-2 by celecoxib and SC-236 completely abolished the migratory response. Overall, our results demonstrate that extracellular S1P induces COX-2 expression via activation of S1P2 and subsequent Gi and p42/p44 MAPK-dependent signaling in renal mesangial cells leading to enhanced PGE2 formation and cell migration that essentially requires COX-2. Thus, targeting S1P/S1P2 signaling pathways might be a novel strategy to treat renal inflammatory diseases.

Relative Energy Balance, CKD, and Risk of Cardiovascular and All-Cause Mortality.

BACKGROUND Mortality risk for people with chronic kidney disease is substantially greater than that for the general population, increasing to a 7-fold greater risk for those on dialysis therapy. Higher body mass index, generally due to higher energy intake, appears protective for people on dialysis therapy, but the relationship between energy intake and survival in those with reduced kidney function is unknown. STUDY DESIGN Prospective cohort study with a median follow-up of 14.5 (IQR, 11.2-15.2) years. SETTING & PARTICIPANTS Blue Mountains Area, west of Sydney, Australia. Participants in the general community enrolled in the Blue Mountains Eye Study (n=2,664) who underwent a detailed interview, food frequency questionnaire, and physical examination including body weight, height, blood pressure, and laboratory tests. PREDICTORS Relative energy intake, food components (carbohydrates, total sugars, fat, protein, and water), and estimated glomerular filtration rate (eGFR). Relative energy intake was dichotomized at 100%, and eGFR, at 60mL/min/1.73m(2). OUTCOMES All-cause and cardiovascular mortality. MEASUREMENTS All-cause and cardiovascular mortality using unadjusted and adjusted Cox proportional regression models. RESULTS 949 people died during follow-up, 318 of cardiovascular events. In people with eGFR<60mL/min/1.73m(2) (n=852), there was an increased risk of all-cause mortality (HR, 1.48; P=0.03), but no increased risk of cardiovascular mortality (HR, 1.59; P=0.1) among those with higher relative energy intake compared with those with lower relative energy intake. Increasing intake of carbohydrates (HR per 100g/d, 1.50; P=0.04) and total sugars (HR per 100g/d, 1.62; P=0.03) was associated significantly with increased risk of cardiovascular mortality. LIMITATIONS Under-reporting of energy intake, baseline laboratory and food intake values only, white population. CONCLUSIONS Increasing relative energy intake was associated with increased all-cause mortality in patients with eGFR<60mL/min/1.73m(2). This effect may be mediated by increasing total sugars intake on subsequent cardiovascular events.

Fluid intake and all-cause mortality, cardiovascular mortality, and kidney function: a population-based longitudinal cohort study

BACKGROUND Drinking eight glasses of fluid or water each day is widely believed to improve health, but evidence is sparse and conflicting. We aimed to investigate the association between fluid consumption and long-term mortality and kidney function. METHODS We conducted a longitudinal analysis within a prospective, population-based cohort study of 3858 men and women aged 49 years or older residing in Australia. Daily fluid intake from food and beverages not including water was measured using a food frequency questionnaire. We did multivariable adjusted Cox proportional hazard models for all-cause and cardiovascular mortality and a boot-strapping procedure for estimated glomerular filtration rate (eGFR). RESULTS Upper and lower quartiles of daily fluid intake corresponded to >3 L and <2 L, respectively. During a median follow-up of 13.1 years (total 43 093 years at risk), 1127 deaths (26.1 per 1000 years at risk) including 580 cardiovascular deaths (13.5 per 1000 years at risk) occurred. Daily fluid intake (per 250 mL increase) was not associated with all-cause [adjusted hazard ratio (HR) 0.99 (95% CI 0.98-1.01)] or cardiovascular mortality [HR 0.98 (95% CI 0.95-1.01)]. Overall, eGFR reduced by 2.2 mL/min per 1.73 m(2) (SD 10.9) in the 1207 (31%) participants who had repeat creatinine measurements and this was not associated with fluid intake [adjusted regression coefficient 0.06 mL/min/1.73 m(2) per 250 mL increase (95% CI -0.03 to 0.14)]. CONCLUSIONS Fluid intake from food and beverages excluding water is not associated with improved kidney function or reduced mortality.

Ein Forschungsreisender als Notbehelf: Hermann von Wissmann und der erste Überseeeinsatz des Deutschen Reichs (1889-1891)

When the German government faced for the first time an irregular war in German East Africa in 1888, it realised that it did not have the necessary means for such a conflict. Hermann Wissmann, an explorer, was therefore given the mandate to form and lead a force of mercenaries that was bound to him personally on the basis of contracts. Although Wissmann was successful in crushing the disturbances, the government of the Reich refused to give him a leading administrative position in the new formed protectorate subordinate directly to the Kaiser. It feared that the entrepreneur of violence, which had up to then been backed up, would not accept the regulations of colonial rule that should be implemented. Soon, however, it became clear that due to entrenched local views on sovereignty and legitimacy it would be difficult to transfer the western European concept of the monopoly of the state on violence to Africa.

The IFNL3/4 ΔG variant increases susceptibility to cytomegalovirus retinitis among HIV-infected patients.

BACKGROUND Cytomegalovirus (CMV) retinitis is a major cause of visual impairment and blindness among patients with uncontrolled HIV infections. Whereas polymorphisms in interferon-lambda 3 (IFNL3, previously named IL28B) strongly influence the clinical course of hepatitis C, few studies examined the role of such polymorphisms in infections due to viruses other than hepatitis C virus. OBJECTIVES To analyze the association of newly identified IFNL3/4 variant rs368234815 with susceptibility to CMV-associated retinitis in a cohort of HIV-infected patients. DESIGN AND METHODS This retrospective longitudinal study included 4884 white patients from the Swiss HIV Cohort Study, among whom 1134 were at risk to develop CMV retinitis (CD4 nadir <100 /μl and positive CMV serology). The association of CMV-associated retinitis with rs368234815 was assessed by cumulative incidence curves and multivariate Cox regression models, using the estimated date of HIV infection as a starting point, with censoring at death and/or lost follow-up. RESULTS A total of 40 individuals among 1134 patients at risk developed CMV retinitis. The minor allele of rs368234815 was associated with a higher risk of CMV retinitis (log-rank test P = 0.007, recessive mode of inheritance). The association was still significant in a multivariate Cox regression model (hazard ratio 2.31, 95% confidence interval 1.09-4.92, P = 0.03), after adjustment for CD4 nadir and slope, HAART and HIV-risk groups. CONCLUSION We reported for the first time an association between an IFNL3/4 polymorphism and susceptibility to AIDS-related CMV retinitis. IFNL3/4 may influence immunity against viruses other than HCV.

Usefulness of electrocardiographic parameters for risk prediction in arrhythmogenic right ventricular dysplasia

The value of electrocardiographic findings predicting adverse outcome in patients with arrhythmogenic right ventricular dysplasia (ARVD) is not well known. We hypothesized that ventricular depolarization and repolarization abnormalities on the 12-lead surface electrocardiogram (ECG) predict adverse outcome in patients with ARVD. ECGs of 111 patients screened for the 2010 ARVD Task Force Criteria from 3 Swiss tertiary care centers were digitized and analyzed with a digital caliper by 2 independent observers blinded to the outcome. ECGs were compared in 2 patient groups: (1) patients with major adverse cardiovascular events (MACE: a composite of cardiac death, heart transplantation, survived sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia, or arrhythmic syncope) and (2) all remaining patients. A total of 51 patients (46%) experienced MACE during a follow-up period with median of 4.6 years (interquartile range 1.8 to 10.0). Kaplan-Meier analysis revealed reduced times to MACE for patients with repolarization abnormalities according to Task Force Criteria (p = 0.009), a precordial QRS amplitude ratio (∑QRS mV V1 to V3/∑QRS mV V1 to V6) of ≤ 0.48 (p = 0.019), and QRS fragmentation (p = 0.045). In multivariable Cox regression, a precordial QRS amplitude ratio of ≤ 0.48 (hazard ratio [HR] 2.92, 95% confidence interval [CI] 1.39 to 6.15, p = 0.005), inferior leads T-wave inversions (HR 2.44, 95% CI 1.15 to 5.18, p = 0.020), and QRS fragmentation (HR 2.65, 95% CI 1.1 to 6.34, p = 0.029) remained as independent predictors of MACE. In conclusion, in this multicenter, observational, long-term study, electrocardiographic findings were useful for risk stratification in patients with ARVD, with repolarization criteria, inferior leads TWI, a precordial QRS amplitude ratio of ≤ 0.48, and QRS fragmentation constituting valuable variables to predict adverse outcome.