Background: Currently there are no disease modifying treatment for Synucleinopathies including Parkinson’s disease Dementia (PDD). Carrying a mutation in the GBA gene (beta-glucocerebrosidase/ GCAse) is a leading risk factor for synucleinopathies. Raising activity GCAse lowers α-synuclein levels in cells and animal models. Ambroxol is a pharmacological chaperone for GCAse and can raise GCAse levels. Our goal is to test Ambroxol as a disease-modifying treatment in PDD. Methods: We randomized fifty-five individuals with PDD to Ambroxol 1050mg/day, 525mg/day, or placebo for 52 weeks. Primary outcome measures included safety, Alzheimer’s disease Assessment Scale-cognitive (ADAS-Cog) subscale and the Clinician’s Global Impression of Change (CGIC). Secondary outcomes included pharmacokinetics, cognitive and motor outcomes and and plasma and CSF biomarkers. Results: Ambroxol was well tolerated. There were 7 serious adverse events (SAEs) none deemed related to Ambroxol. GCase activity was increased in white blood cells by ~1.5 fold. There were no differences between groups on primary outcome measures. Patients receiving high dose Ambroxol appeared better on the Neuropsychiatric Inventory. GBA carriers appeared to improve on some cognitive tests. pTau 181 was reduced in CSF. Conclusions: Ambroxol was safe and well-tolerated in PDD. Ambroxol may improve biomarkers and cognitive outcomes in GBA1 mutation carrie.rs Ambroxol improved some biomarkerss. ClinicalTrials.gov NCT02914366

Although human factors are recognized as influential factors affecting the welfare and productivity of farm animals, only limited research has been conducted to identify these important human characteristics and to quantify their effects. During the last 13 years we have studied two apparently important human factors: the attitude and the behaviour of stockpersons towards farm animals.

We have proposed that in intensive animal production systems there are some important sequential relationships between the attitude and behaviour of the stockperson towards farm animals and the behaviour, performance and welfare of farm animals. Basically we have suggested that because a stockperson's behaviour towards animals is largely under volitional control it is strongly influenced by the attitudes and beliefs that the stockperson holds about the animals. Furthermore, the stockperson's behaviour towards animals affects the animals’ fear of humans which, in turn, affects the animals’ productivity and welfare. It is the occurrence of a stress response by animals which are highly fearful of humans which places their productivity and welfare at risk We have published data which strongly support these interrelationships between human attitude and behaviour and animal behaviour, productivity and welfare. This paper reviews this and other research on this subject. The results of research in the pig industry and to a lesser extent, the poultry industries indicate the excellent opportunity which exists to improve animal productivity and welfare by training and selecting stockpersons to have desirable attitudinal and behavioural profiles towards farm animals.

Between 2010 and 2019 the international health care organization Partners In Health (PIH) and its sister organization Zanmi Lasante (ZL) mounted a long-term response to the 2010 Haiti earthquake, focused on mental health. Over that time, implementing a Theory of Change developed in 2012, the organization successfully developed a comprehensive, sustained community mental health system in Haiti's Central Plateau and Artibonite departments, directly serving a catchment area of 1.5 million people through multiple diagnosis-specific care pathways. The resulting ZL mental health system delivered 28 184 patient visits and served 6305 discrete patients at ZL facilities between January 2016 and September 2019. The experience of developing a system of mental health services in Haiti that currently provides ongoing care to thousands of people serves as a case study in major challenges involved in global mental health delivery. The essential components of the effort to develop and sustain this community mental health system are summarized.

Furnished cage housing for laying hens has been introduced in some countries as a ‘welfare-friendly’ alternative to conventional cage systems. Whether this housing system would be acceptable to the public remains unknown. This pilot study aimed to engage the public through online discussions in order to investigate their knowledge, support and perception of laying hen welfare housed in furnished cages. During these discussions, a science-based information statement about furnished cages was introduced. Through a mixed method approach, surveys to assess beliefs and knowledge were administered to participants before and after the online discussion. We qualitatively analysed the online discussion transcripts to determine recurrent themes, and quantitatively measured levels of knowledge and support for furnished cages using pre- and post-forum surveys. Support for the introduction increased from 55% pre-forum to 65% post-forum. Additionally, the participants’ perceived welfare of laying hens in furnished cages and objective knowledge of furnished cages significantly increased after online discussion. These results suggest that engagement with the public combined with the delivery of science-based information may be important factors when considering whether to introduce new farming practices. Trust in industry through transparency and willingness to engage in discussions with the public might also mitigate public concerns.

There is community concern about the treatment of farm animals post-farm gate, particularly animal transport and slaughter. Relationships between lamb behavioural and physiological variables on farm, stockperson, dog and lamb behavioural variables pre-slaughter and plasma cortisol, glucose and lactate in lambs post-slaughter were studied in 400 lambs. The lambs were observed in three behavioural tests, novel arena, flight distance to a human and temperament tests, before transport for slaughter. Closed-circuit television video footage was used to record stockperson, dog and lamb behaviour immediately before slaughter. Blood samples for cortisol, glucose and lactate analyses were collected on farm following the three behavioural tests and immediately post-slaughter. The regression models that best predicted plasma cortisol, glucose and lactate concentrations post-slaughter included a mixture of stockperson and dog behavioural variables as well as lamb variables both on-farm and pre-slaughter. These regression models accounted for 33%, 34% and 44% of the variance in plasma cortisol, glucose and lactate concentrations post-slaughter, respectively. Some of the stockperson and dog behaviours pre-slaughter that were predictive of the stress and metabolic variables post-slaughter included the duration of negative stockperson behaviours such as fast locomotion and lifting/pulling lambs, and the duration of dog behaviours such as lunging and barking at the lamb, while some of the predictive lamb behaviour variables included the durations of jumping and fleeing. Some of the physiological and behavioural responses to the behavioural tests on farm were also predictive of the stress and metabolic variables post-slaughter. These relationships support the well-demonstrated effect of handling on fear and stress responses in livestock, and although not direct evidence of causal relationships, highlight the potential benefits of training stockpeople to reduce fear and stress in sheep at abattoirs.

The dietary inflammatory index (DIITM) is a novel composite score based on a range of nutrients and foods known to be associated with inflammation. DII scores have been linked to the risk of a number of cancers, including oesophageal squamous cell cancer and oesophageal adenocarcinoma (OAC). Given that OAC stems from acid reflux and that the oesophageal epithelium undergoes a metaplasia-dysplasia transition from the resulting inflammation, it is plausible that a high DII score (indicating a pro-inflammatory diet) may exacerbate risk of OAC and its precursor conditions. The aim of this analytical study was to explore the association between energy-adjusted dietary inflammatory index (E-DIITM) in relation to risk of reflux oesophagitis, Barrett’s oesophagus and OAC. Between 2002 and 2005, reflux oesophagitis (n 219), Barrett’s oesophagus (n 220) and OAC (n 224) patients, and population-based controls (n 256), were recruited to the Factors influencing the Barrett’s Adenocarcinoma Relationship study in Northern Ireland and the Republic of Ireland. E-DII scores were derived from a 101-item FFQ. Unconditional logistic regression analysis was applied to determine odds of oesophageal lesions according to E-DII intakes, adjusting for potential confounders. High E-DII scores were associated with borderline increase in odds of reflux oesophagitis (OR 1·87; 95 % CI 0·93, 3·73), and significantly increased odds of Barrett’s oesophagus (OR 2·05; 95 % CI 1·22, 3·47), and OAC (OR 2·29; 95 % CI 1·32, 3·96), when comparing the highest with the lowest tertiles of E-DII scores. In conclusion, a pro-inflammatory diet may exacerbate the risk of the inflammation-metaplasia-adenocarcinoma pathway in oesophageal carcinogenesis.

In the spring of 1995 an extensive global positioning system (GPS) survey was carried out on the Amery Ice Shelf, East Antarctica, providing ground-truth ellipsoidal height measurements for the European remote-sensing satellite (ERS) radar altimeters. GPS- and altimeter-derived surface heights have been compared at the intersecting points of the ERS ground tracks and the GPS survey. The mean and rms height difference for all ERS-1 geodetic-phase tracks across the survey region is 0.0 + 0.1 m and 1.7 m, respectively. The spatial distribution of the height differences is highly correlated with surface topographic variations. Comparisons of GPS-derived surface-elevation profiles along ERS ground tracks show that the ERS altimeters can closely follow the GPS representation of the actual surface.

Evidence suggests a role of Mg and the ratio of Ca:Mg intakes in the prevention of colonic carcinogenesis. The association between these nutrients and oesophageal adenocarcinoma – a tumour with increasing incidence in developed countries and poor survival rates – has yet to be explored. The aim of this investigation was to explore the association between Mg intake and related nutrients and risk of oesophageal adenocarcinoma and its precursor conditions, Barrett’s oesophagus and reflux oesophagitis. This analysis included cases of oesophageal adenocarcinoma (n 218), Barrett’s oesophagus (n 212), reflux oesophagitis (n 208) and population-based controls (n 252) recruited between 2002 and 2005 throughout the island of Ireland. All the subjects completed a 101-item FFQ. Unconditional logistic regression analysis was applied to determine odds of disease according to dietary intakes of Mg, Ca and Ca:Mg ratio. After adjustment for potential confounders, individuals consuming the highest amounts of Mg from foods had significant reductions in the odds of reflux oesophagitis (OR 0·31; 95 % CI 0·11, 0·87) and Barrett’s oesophagus (OR 0·29; 95 % CI 0·12, 0·71) compared with individuals consuming the lowest amounts of Mg. The protective effect of Mg was more apparent in the context of a low Ca:Mg intake ratio. No significant associations were observed for Mg intake and oesophageal adenocarcinoma risk (OR 0·77; 95 % CI 0·30, 1·99 comparing the highest and the lowest tertiles of consumption). In conclusion, dietary Mg intakes were inversely associated with reflux oesophagitis and Barrett’s oesophagus risk in this Irish population.

Direct numerical simulation (DNS) of a time-developing turbulent wake evolving in a stably stratified background is presented. A large initial Froude number is chosen to allow the wake to become fully turbulent and axisymmetric before stratification affects the spreading rate of the mean defect. Turbulence statistics are formed by averaging over the homogeneous streamwise direction of a domain that is larger than earlier stratified-wake simulations in order to reduce the statistical uncertainty. The DNS results are used to cast light on the mechanisms that lead to the various states of this flow – namely the three-dimensional (essentially unstratified), non-equilibrium (or ‘wake-collapse’) and quasi-two-dimensional (or ‘two-component’) regimes, previously observed for wakes embedded in both weakly and strongly stratified backgrounds. For this relatively high-initial-Reynolds- and Froude-number simulation, we find that the signature reduction in the rate of decay of the maximum mean defect velocity during the wake-collapse regime is due to buoyancy-induced alterations of the turbulence structure, which weaken and redistribute the Reynolds shear stresses whose gradients appear in the streamwise mean momentum equation. The change in the rate of decay of the turbulence kinetic energy (TKE) observed during the wake-collapse regime (which occurs well after the mean velocity decay reduction begins) is not caused by transfer of turbulent gravitational potential energy to TKE, as has been previously suggested. The results instead reveal that the reduction in TKE decay – which for this flow, with its relatively weak internal waves, eventually leads to TKE growth, heralding the arrival of the two-component regime – is caused by an increase in the rate of TKE production associated with the wake structure becoming increasingly two-dimensional, such that the lateral Reynolds shear stress, $-\overline{u^{\prime }v^{\prime }}$, becomes dominant. The present results are also compared with those of previous simulations at different Froude and Reynolds numbers, and whose initial conditions contain different turbulence structures. This comparison confirms a strong degree  of commonality in the late-wake behaviour, which lends support to the hypothesis that all wakes in stably stratified environments achieve a universal state in the final stages of decay.

This article provides practical ethical guidance for clinicians making decisions after a nuclear detonation, in advance of the full establishment of a coordinated response. We argue that the utilitarian maxim of the greatest good for the greatest number, interpreted only as “the most lives saved,” needs refinement. We take the philosophical position that utilitarian efficiency should be tempered by the principle of fairness in making decisions about providing lifesaving interventions and palliation. The most practical way to achieve these goals is to mirror the ethical precepts of routine clinical practice, in which 3 factors govern resource allocation: order of presentation, patient's medical need, and effectiveness of an intervention. Although these basic ethical standards do not change, priority is given in a crisis to those at highest need in whom interventions are expected to be effective. If available resources will not be effective in meeting the need, then it is unfair to expend them and they should be allocated to another patient with high need and greater expectation for survival if treated. As shortage becomes critical, thresholds for intervention become more stringent. Although the focus of providers will be on the victims of the event, the needs of patients already receiving care before the detonation also must be considered. Those not allocated intervention must still be provided as much appropriate comfort, assistance, relief of symptoms, and explanations as possible, given the available resources. Reassessment of patients' clinical status and priority for intervention also should be conducted with regularity.

(Disaster Med Public Health Preparedness. 2011;5:S46-S53)

This paper was written by the Derivatives Working Party, a permanent working party of the Life Research Committee of the Institute and Faculty of Actuaries. Our aim is to consider how life assurers may use, or may wish to use, derivatives, and if their use is unduly constrained, e.g. by regulation. This paper focuses on credit derivatives. We provide an overview of the credit derivatives market, and the strong growth in this market over recent years. We then focus on the two main traded credit derivative instruments — Credit Default Swaps (CDSs) and Collateralised Debt Obligations (CDOs). We explain how these instruments work and are priced, and clarify some of the more complex topics involved, such as the settlement of CDSs, basis risk and the relevance of implied correlation in pricing CDOs. We then consider how life insurers could make use of credit derivatives, for example to provide more efficient investment management in taking exposure to credit risk, or to hedge credit exposures, and consider the regulatory implications of so doing. Finally, in the Appendix, we discuss the credit spread puzzle, and the existence or otherwise of a liquidity premium in corporate bond spreads, with implications for the valuation of illiquid liabilities.

Direct numerical simulation is used to study the development of a single laminar vortex ring as it impinges on a free surface directly from below. We consider the limiting case in which the Froude number approaches zero and the surface can be modelled with a stress-free rigid and impermeable boundary. We find that as the ring expands in the radial direction close to the surface, the natural Tsai–Widnall–Moore–Saffman (TWMS) instability is superseded by the development of the Crow instability. The Crow instability is able to further amplify the residual perturbations left by the TWMS instability despite being of differing radial structure and alignment. This occurs through realignment of the instability structure and shedding of a portion of its outer vorticity profile. As a result, the dominant wavenumber of the Crow instability reflects that of the TWMS instability, and is dependent upon the initial slenderness ratio of the ring. At higher Reynolds number a short-wavelength instability develops on the long-wavelength Crow instability. The wavelength of the short waves is found to vary around the ring dependent on the local displacement of the long waves.

This paper reports a qualitative study that used narrative analysis to explore how social support helps many armed-services veterans cope with traumatic memories. The analysis was carried out on two levels, that of narrative form (level of narrative coherence), argued to be indicative of reconciliation, and narrative content (themes of social support), which allowed exploration of the types of social support experienced by veterans with coherent, reconciled and incoherent narratives. Ten British male Second World War veterans were interviewed regarding their war experiences, presence of traumatic memories, and experiences of social support from comrades, family and society. Different patterns of support were qualitatively related to coherent, reconciled and incoherent narratives. Veterans with coherent narratives were no less likely to have experienced traumatic events than those with reconciled or incoherent narratives, but they reported more positive perceptions of their war experience and of the war's outcomes, more positive experiences of communication with family in later life, and more positive perceptions of societal opinion. The results are discussed in relation to how veterans can be supported by family and friends to reconcile their traumatic memories, thus to lessen the burden in later life when vital support resources may be unavailable.

Serum and cervical secretions were collected from patients with cervical dysplasia, carcinoma-in-situ (CIS), squamous cell carcinoma (cervical SCC), and controls with normal cervices, attending clinics within the West Lambeth Health District, London. Enzyme-linked immunosorbent assays were used to examine cervical secretory IgA (sIgA) and serum IgG and IgA antibodies to herpes simplex virus (HSV). Sexual and demographic factors were considered during data analysis, which involved fitting multiple linear or multiple logistic regressions to HSV antibody levels. Prevalence of sIgA-HSV and levels of serum antibodies to HSV in all groups were compared with those of gynaecology controls. Caucasian women with mild dysplasia had a significantly higher prevalence of sIgA-HSV. Serum IgG levels to HSV (IgG-HSV) were significantly elevated in women with mild dysplasia and severe dysplasia/ClS. Serum IgA levels to HSV1 (IgG-HSV1) were significantly higher in women with cervical SCC (after adjusting for smoking habits) and other genital tumours. Significantly higher levels of serum IgA to HSV2 (IgA-HSV2) were also found among Caucasian women with cervical SCC. The possible role of HSV as a co-factor in cervical carcinogenesis is discussed.

Although a variety of research projects have been conducted on the benefits of religious coping in older adults, no direct comparison between atheism and religious faith has been published. The study reported in this paper tackled this issue by interviewing two matched groups of people aged over 60 years living in southern England, one of 11 informants with strong atheistic beliefs, and the other of eight informants with strong religious beliefs. Five paired comparisons were undertaken to examine the role of the content of the belief system itself in coping with different negative stresses and losses commonly associated with ageing and old age. The pairs were matched for the nature of the loss or stress that the two people had experienced, but the two individuals had opposed atheistic and religious beliefs. The analyses showed that all the study participants – regardless of their beliefs – were coping well, and suggested that a strong atheistic belief system can fulfil the same role as a strong religious belief system in providing support, explanation, consolation and inspiration. It is postulated that the strength of people's beliefs and how those beliefs are used might have more influence on the efficacy of coping than the specific nature of the beliefs. Further research into the strength of belief systems, including atheism, is required to test and elaborate this hypothesis.