Harvest Shortfalls, Grain prices, and Famines in Preindustrial England

The frequency of bad harvests and price elasticity of demand are measured using new data on English grain yields 1268–1480 and 1750–1850 and a revised price series. The analysis shows that major harvest shortfalls were a significant component of most historical subsistence crises, as back-to-back shortfalls were of the worst famines. Although serious harvest shortfalls long remained an unavoidable fact of economic life, by c.1800 yields had become less variable and prices less harvest sensitive. By the eve of the Industrial Revolution, England had become effectively famine-free.

Quality of life in screen-detected and typical coeliac disease and the effect of excluding dietary gluten

It is widely recognized that 'asymptomatic' patients with coeliac disease often feel better after commencing a gluten-free diet. The aim of this study was to determine a measure of the quality of life in patients diagnosed as having coeliac disease detected both by screening and those with typical clinical symptoms.

Intragastric bile acid concentrations are unrelated to symptoms of flatulent dyspepsia in patients with and without gallbladder disease and postcholecystectomy

It has been proposed that duodenogastric reflux may be the basic underlying mechanism which gives rise to symptoms of flatulent dyspepsia. Fasting and postprandial gastric juice bile acid concentrations were measured in patients with flatulent dyspepsia with and without gall bladder disease and postcholecystectomy. There were 13 patients with gall bladder disease, 12 with normal gall bladders and 13 postcholecystectomy. Gastric juice was obtained by intubation. Bile acid concentrations were compared with 21 controls and 15 asymptomatic subjects with gall bladder disease. For 21 patients with gall bladder disease who underwent cholecystectomy, levels were again assessed postoperatively to allow correlation with outcome. The occurrence of reflux and the resultant gastric juice bile acids did not correlate with symptoms. Concentrations postcholecystectomy, including asymptomatic subjects were significantly higher than controls (p less than 0.01). It is concluded that limited duodenogastric reflux is common and need not be associated with symptoms even when the resultant intra-gastric concentrations are higher than normal.

Cognitive, global, and functional benefits of donepezil in Alzheimer's disease and vascular dementia:results from large-scale clinical trials

Alzheimer's disease (AD) and vascular dementia (VaD) are both associated with deficits in cholinergic neurotransmission that are amenable to therapeutic intervention. The cholinesterase inhibitor, donepezil, is clinically effective in both AD and VaD. Results from a 10-study metaanalysis of donepezil (5 or 10 mg/day) in AD and a two-study combined analysis of donepezil (5 or 10 mg/day) in VaD are presented to compare patient characteristics and donepezil treatment outcomes. The analyzed studies were randomized, placebo-controlled, and of up to 24 weeks duration. In both AD and VaD, donepezil provided significant benefits compared with placebo on measures of cognition and global function. Placebo-treated AD patients showed a decline in cognition and global function, whereas placebo-treated VaD patients remained stable, suggesting treatment effects of donepezil in VaD were driven by improvement rather than stabilization or reduced decline. More VaD patients than AD patients received concomitant medications. Cardiovascular adverse events were more common in VaD than AD patients but were not increased by donepezil. In conclusion, although there are differences between AD and VaD patients in comorbid conditions and concomitant medications, donepezil is effective and well tolerated in both types of dementia.

Plasma somatostatin and gastrointestinal peptides in Alzheimer's disease and vascular dementia

Few markers distinguish between different dementia types. As dementia affects many body systems outside the central nervous system, we investigated gastrointestinal regulatory peptides as possible disease markers in Alzheimer's Disease (AD) and vascular dementia (VaD). Subjects with mild-to-moderate dementia were diagnosed as probable AD and VaD according to defined criteria. Gastrointestinal peptides were stimulated using a standardized meal test, administered after an overnight fast to 58 dementia patients (40 AD, 18 VaD) and 47 controls matched for age and sex. Blood samples were taken at designated time intervals, and basal and stimulated plasma concentrations of eleven peptides were determined by radio-immunoassay. Results were analysed using the Kruskal-Wallis one-way analysis of variance; the Mann-Whitney U test was used in post hoc analysis where appropriate. There were significant differences in somatostatin levels but in none of the other peptides. Basal somatostatin was significantly increased in VaD compared to controls (p

Alzheimer's disease and age-related macular degeneration have different genetic models for complement gene variation

Alzheimer's disease (AD) and age-related macular degeneration (AMD) are both neurodegenerative disorders which share common pathological and biochemical features of the complement pathway. The aim of this study was to investigate whether there is an association between well replicated AMD genetic risk factors and AD. A large cohort of AD (n = 3898) patients and controls were genotyped for single nucleotide polymorphisms (SNPs) in the complement factor H (CFH), the Age-related maculopathy susceptibility protein 2 (ARMS2) the complement component 2 (C2), the complement factor B (CFB), and the complement component 3 (C3) genes. While significant but modest associations were identified between the complement factor H, the age-related maculopathy susceptibility protein 2, and the complement component 3 single nucleotide polymorphisms and AD, these were different in direction or genetic model to that observed in AMD. In addition the multilocus genetic model that predicts around a half of the sibling risk for AMD does not predict risk for AD. Our study provides further support to the hypothesis that while activation of the alternative complement pathway is central to AMD pathogenesis, it is less involved in AD.

The alterations of Ca2+/Calmodulin/CaMKII/CaV1.2 signaling in experimental models of Alzheimer's disease and vascular dementia

The two critical forms of dementia are Alzheimer's disease (AD) and vascular dementia (VD).The alterations of Ca2+/calmodulin/CaMKII/CaV1.2 signaling in AD and VD have not been well elucidated. Here we have demonstrated changes in the levels of CaV1.2, calmodulin, p-CaMKII, p-CREB and BDNF proteins by Western blot analysis and the co-localization of p-CaMKII/CaV1.2 by double-labeling immunofluorescence in the hippocampus of APP/PS1 mice and VD gerbils. Additionally, expression of these proteins and intracellular calcium levels were examined in cultured neurons treated with Aß1–42. The expression of CaV1.2 protein was increased in VD gerbils and in cultured neurons but decreased in APP/PS1 mice; the expression of calmodulin protein was increased in APP/PS1 mice and VD gerbils; levels of p-CaMKII, p-CREB and BDNF proteins were decreased in AD and VD models. The number of neurons in which p-CaMKII and CaV1.2 were co-localized, was decreased in the CA1 and CA3 regions in two models. Intracellular calcium was increased in the cultured neurons treated with Aß1–42. Collectively, our results suggest that the alterations in CaV1.2, calmodulin, p-CaMKII, p-CREB and BDNF can be reflective of an involvement in the impairment in memory and cognition in AD and VD models.

The experiences of palliative care health service provision for people with non-malignant respiratory disease and their caregivers: an all-Ireland study

Aim: To explore the perception of palliative care provision for people with non-malignant respiratory disease from the perspective of bereaved caregivers.

Background: It is recognized that the majority of patients diagnosed with a malignant disease will have access to palliative care provision. However, it is less clear if the same standards of palliative care are available to those with non-malignant respiratory disease in Northern Ireland and the Republic of Ireland.

Design: A qualitative study based on broad interpretivism.

Methods: This research is a PhD study funded by the Department of Education and Learning in Northern Ireland (awarded February 2011). Data collection will consist of two stages; interviews with 20 bereaved caregivers of people who have died 3–18 months previously with a diagnosis of non-malignant respiratory disease and four focus groups with healthcare professionals involved in the care of this client group. This study will be carried out at four healthcare sites across the Island of Ireland. The data will be analysed using thematic content analysis. Research Ethics committee approval was obtained (March 2012).

Discussion: This research will explore the experiences of patients with Chronic Obstructive Pulmonary Disease, Interstitial Lung Disease and Bronchiectasis and their caregivers from the perspective of the bereaved caregiver. The outcomes of this study will provide a critical first step in the development of more responsive palliative care for this client group and have important implications for future practice and policy in the palliative care provided to this client group.

Desire for hastened death in patients with advanced disease and the evidence base of clinical guidelines:a systematic review

Patients' desire for hastened death within the context of advanced disease and palliative care is a controversial topic, frequently discussed in the international literature. Much of the discussion has focused on opinion and debate about ethical matters related to hastened death. Not many research studies seem to have specifically targeted why palliative care patients may desire hastened death, and few have focused on clinical guidelines for responding to such requests.

How well do family caregivers cope after caring for a relative with advanced disease and how can health professionals enhance their support?

Support for families during a person's advanced disease and also into the bereavement period is a major component of palliative care. However, because of the gaps in bereavement research in this area, there is a lack of evidence-based direction for health professionals.

A literature review of end-stage renal disease and cachexia:Understanding experience to inform evidence-based healthcare

Introduction: Cachexia is a major cause of morbidity and mortality in people who have end-stage renal disease (ESRD). The majority of research into cachexia in ESRD has focused on the biological aspects of the syndrome and potential treatment modalities. While this research is necessary, it predominately focuses on the physical impact of cachexia in ESRD. The multi-dimensional psychosocial ramifications of this syndrome have been highlighted in other end-stage illness trajectories, but have not been systematically explored in persons who have ESRD. Aim: This paper discusses why this research is necessary, alongside further studies to help define the pathophysiology of this syndrome. Conclusion: The rich insightful data gained from understanding the patients' illness experience will positively contribute to the limited knowledge base available and inform future holistic patient-centred care delivery which recognises and responds to not only the biological but also the psychosocial impact of cachexia. © 2013 European Dialysis and Transplant Nurses Association/European Renal Care Association.

Multiple Regulatory Pathways Associated with High-Level Ciprofloxacin and Multidrug Resistance in Salmonella enterica Serovar Enteritidis: Involvement of ramA and Other Global Regulators

Mechanisms of antibiotic resistance were examined in nalidixic acid-resistant Salmonella enterica serovar Enteritidis field isolates displaying decreased susceptibility to ciprofloxacin and in in vitro-derived ciprofloxacin-resistant mutants (104-cip and 5408-cip). All field isolates harbored a single gyrA mutation (D87Y). Deletion of acrB and complementation with wild-type gyrA increased quinolone susceptibility. Selection for ciprofloxacin resistance was associated with the development of an additional gyrA (S83F) mutation in 104-cip, novel gyrB (E466D) and parE (V461G) mutations in 5408-cip, overexpression of acrB and decreased susceptibility to nonquinolone antibiotics in both mutants, and decreased OmpF production and altered lipopoly- saccharide in 104-cip. Complementation of mutated gyrA and gyrB with wild-type alleles restored susceptibility to quinolones in 104-cip and significantly decreased the ciprofloxacin MIC in 5408-cip. Complementation of parE had no effect on quinolone MICs. Deletion of acrB restored susceptibility to ciprofloxacin and other antibiotics tested. Both soxS and marA were overexpressed in 104-cip, and ramA was overexpressed in 5408-cip. Inactivation of each of these global regulators lowered ciprofloxacin MICs, decreased expression of acrB, and restored susceptibility to other antibiotics. Mutations were found in soxR (R20H) and in soxS (E52K) in 104-cip and in ramR (G25A) in 5408-cip. In conclusion, both efflux activity and a single gyrA mutation contribute to nalidixic acid resistance and reduced ciprofloxacin sensitivity. Ciprofloxacin resistance and decreased susceptibility to multiple antibiotics can result from different genetic events leading to development of target gene mutations, increased efflux activity resulting from differential expression of global regulators associated with mutations in their regulatory genes, and possible altered membrane permeability.

Survival in dialysis patients is different between patients with diabetes as primary renal disease and patients with diabetes as a co-morbid condition.

AIMS/HYPOTHESIS:

A previous study in Dutch dialysis patients showed no survival difference between patients with diabetes as primary renal disease and those with diabetes as a co-morbid condition. As this was not in line with our hypothesis, we aimed to verify these results in a larger international cohort of dialysis patients.

METHODS:

For the present prospective study, we used data from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry. Incident dialysis patients with data on co-morbidities (n?=?15,419) were monitored until kidney transplantation, death or end of the study period (5 years). Cox regression was performed to compare survival for patients with diabetes as primary renal disease, patients with diabetes as a co-morbid condition and non-diabetic patients.

RESULTS:

Of the study population, 3,624 patients (24%) had diabetes as primary renal disease and 1,193 (11%) had diabetes as a co-morbid condition whereas the majority had no diabetes (n?=?10,602). During follow-up, 7,584 (49%) patients died. In both groups of diabetic patients mortality was higher compared with the non-diabetic patients. Mortality was higher in patients with diabetes as primary renal disease than in patients with diabetes as a co-morbid condition, adjusted for age, sex, country and malignancy (HR 1.20, 95% CI 1.10, 1.30). An analysis stratified by dialysis modality yielded similar results.

CONCLUSIONS/INTERPRETATION:

Overall mortality was significantly higher in patients with diabetes as primary renal disease compared with those with diabetes as a co-morbid condition. This suggests that survival in diabetic dialysis patients is affected by the extent to which diabetes has induced organ damage.