A Large-Scale FPGA-Based Trigger and Dead-Time Free DAQ System for the Kaos Spectrometer at MAMI

The Kaos spectrometer is maintained by the A1 collaboration at the Mainz Microtron MAMI with a focus on the study of (e,e'K^+) coincidence reactions. For its electron-arm two vertical planes of fiber arrays, each comprising approximately 10 000 fibers, are operated close to zero degree scattering angle and in close proximity to the electron beam. A nearly dead-time free DAQ system to acquire timing and tracking information has been installed for this spectrometer arm. The signals of 144 multi-anode photomultipliers are collected by 96-channel front-end boards, digitized by double-threshold discriminators and the signal time is picked up by state-of-the-art F1 time-to-digital converter chips. In order to minimize background rates a sophisticated trigger logic was implemented in newly developed Vuprom modules. The trigger performs noise suppression, signal cluster finding, particle tracking, and coincidence timing, and can be expanded for kinematical matching (e'K^+) coincidences. The full system was designed to process more than 4 000 read-out channels and to cope with the high electron flux in the spectrometer and the high count rate requirement of the detectors. It was successfully in-beam tested at MAMI in 2009.Comment: Contributed to 17th IEEE Real Time Conference (RT10), Lisbon, 24-28 May 201

Symptoms and quality of life in late stage Parkinson syndromes: a longitudinal community study of predictive factors

BACKGROUND Palliative care is increasingly offered earlier in the cancer trajectory but rarely in Idiopathic Parkinson's Disease(IPD), Progressive Supranuclear Palsy(PSP) or Multiple System Atrophy(MSA). There is little longitudinal data of people with late stage disease to understand levels of need. We aimed to determine how symptoms and quality of life of these patients change over time; and what demographic and clinical factors predicted changes. METHODS We recruited 82 patients into a longitudinal study, consenting patients with a diagnosis of IPD, MSA or PSP, stages 3-5 Hoehn and Yahr(H&Y). At baseline and then on up to 3 occasions over one year, we collected self-reported demographic, clinical, symptom, palliative and quality of life data, using Parkinson's specific and generic validated scales, including the Palliative care Outcome Scale (POS). We tested for predictors using multivariable analysis, adjusting for confounders. FINDINGS Over two thirds of patients had severe disability, over one third being wheelchair-bound/bedridden. Symptoms were highly prevalent in all conditions - mean (SD) of 10.6(4.0) symptoms. More than 50% of the MSA and PSP patients died over the year. Over the year, half of the patients showed either an upward (worsening, 24/60) or fluctuant (8/60) trajectory for POS and symptoms. The strongest predictors of higher levels of symptoms at the end of follow-up were initial scores on POS (AOR 1.30; 95%CI:1.05-1.60) and being male (AOR 5.18; 95% CI 1.17 to 22.92), both were more predictive than initial H&Y scores. INTERPRETATION The findings point to profound and complex mix of non-motor and motor symptoms in patients with late stage IPD, MSA and PSP. Symptoms are not resolved and half of the patients deteriorate. Palliative problems are predictive of future symptoms, suggesting that an early palliative assessment might help screen for those in need of earlier intervention

Palliative care in urgent need of recognition and development in general practice: the example of Germany

Background: Specialist palliative care is being increasingly recognised and developed to improve end-of-life care in many developed countries. However, only a small proportion of the total number of patients with incurable, progressive diseases actually has direct contact with specialist palliative care practitioners. Using the German situation as an example, the main purpose of this paper is to argue that the emphasis on specialist palliative care services without a similar encouragement of primary palliative care will deliver a constrained service

The Na(+)–H(+ )exchanger-1 induces cytoskeletal changes involving reciprocal RhoA and Rac1 signaling, resulting in motility and invasion in MDA-MB-435 cells

INTRODUCTION: An increasing body of evidence shows that the tumour microenvironment is essential in driving neoplastic progression. The low serum component of this microenvironment stimulates motility/invasion in human breast cancer cells via activation of the Na(+)–H(+ )exchanger (NHE) isoform 1, but the signal transduction systems that underlie this process are still poorly understood. We undertook the present study to elucidate the role and pattern of regulation by the Rho GTPases of this serum deprivation-dependent activation of both NHE1 and subsequent invasive characteristics, such as pseudopodia and invadiopodia protrusion, directed cell motility and penetration of normal tissues. METHODS: The present study was performed in a well characterized human mammary epithelial cell line representing late stage metastatic progression, MDA-MB-435. The activity of RhoA and Rac1 was modified using their dominant negative and constitutively active mutants and the activity of NHE1, cell motility/invasion, F-actin content and cell shape were measured. RESULTS: We show for the first time that serum deprivation induces NHE1-dependent morphological and cytoskeletal changes in metastatic cells via a reciprocal interaction of RhoA and Rac1, resulting in increased chemotaxis and invasion. Deprivation changed cell shape by reducing the amount of F-actin and inducing the formation of leading edge pseudopodia. Serum deprivation inhibited RhoA activity and stimulated Rac1 activity. Rac1 and RhoA were antagonistic regulators of both basal and stimulated tumour cell NHE1 activity. The regulation of NHE1 activity by RhoA and Rac1 in both conditions was mediated by an alteration in intracellular proton affinity of the exchanger. Interestingly, the role of each of these G-proteins was reversed during serum deprivation; basal NHE1 activity was regulated positively by RhoA and negatively by Rac1, whereas RhoA negatively and Rac1 positively directed the stimulation of NHE1 during serum deprivation. Importantly, the same pattern of RhoA and Rac1 regulation found for NHE1 activity was observed in both basal and serum deprivation dependent increases in motility, invasion and actin cytoskeletal organization. CONCLUSION: Our findings suggest that the reported antagonistic roles of RhoA and Rac1 in cell motility/invasion and cytoskeletal organization may be due, in part, to their concerted action on NHE1 activity as a convergence point

Psychological process from hospitalization to death among uninformed terminal liver cancer patients in Japan

BACKGROUND: Although the attitude among doctors toward disclosing a cancer diagnosis is becoming more positive, informing patients of their disease has not yet become a common practice in Japan. We examined the psychological process, from hospitalization until death, among uninformed terminal cancer patients in Japan, and developed a psychological model. METHODS: Terminal cancer patients hospitalized during the recruiting period voluntarily participated in in-depth interviews. The data were analyzed by grounded theory. RESULTS: Of the 87 uninformed participants at the time of hospitalization, 67% (N = 59) died without being informed of their diagnosis. All were male, 51–66 years of age, and all experienced five psychological stages: anxiety and puzzlement, suspicion and denial, certainty, preparation, and acceptance. At the end of each stage, obvious and severe feelings were observed, which were called "gates." During the final acceptance stage, patients spent a peaceful time with family, even talking about their dreams with family members. CONCLUSION: Unlike in other studies, the uninformed patients in this study accepted death peacefully, with no exceptional cases. Despite several limitations, this study showed that almost 70% of the uninformed terminal cancer patients at hospitalization died without being informed, suggesting an urgent need for culturally specific and effective terminal care services for cancer patients in Japan

National strategy for palliative care of severely ill and dying people and their relatives in pandemics (PallPan) in Germany - study protocol of a mixed-methods project

BACKGROUND In the SARS-CoV-2 pandemic, general and specialist Palliative Care (PC) plays an essential role in health care, contributing to symptom control, psycho-social support, and providing support in complex decision making. Numbers of COVID-19 related deaths have recently increased demanding more palliative care input. Also, the pandemic impacts on palliative care for non-COVID-19 patients. Strategies on the care for seriously ill and dying people in pandemic times are lacking. Therefore, the program 'Palliative care in Pandemics' (PallPan) aims to develop and consent a national pandemic plan for the care of seriously ill and dying adults and their informal carers in pandemics including (a) guidance for generalist and specialist palliative care of patients with and without SARS-CoV-2 infections on the micro, meso and macro level, (b) collection and development of information material for an online platform, and (c) identification of variables and research questions on palliative care in pandemics for the national pandemic cohort network (NAPKON). METHODS Mixed-methods project including ten work packages conducting (online) surveys and qualitative interviews to explore and describe i) experiences and burden of patients (with/without SARS-CoV-2 infection) and their relatives, ii) experiences, challenges and potential solutions of health care professionals, stakeholders and decision makers during the SARS-CoV-2 pandemic. The work package results inform the development of a consensus-based guidance. In addition, best practice examples and relevant literature will be collected and variables for data collection identified. DISCUSSION For a future \textquotedblpandemic preparedness\textquotedbl national and international recommendations and concepts for the~care of severely ill and dying people are necessary considering both generalist and specialist palliative care in the home care and inpatient setting

Challenges in supporting lay carers of patients at the end of life: results from focus group discussions with primary healthcare providers

Background: Family caregivers (FCGs) of patients at the end of life (EoL) cared for at home receive support from professional and non-professional care providers. Healthcare providers in general practice play an important role as they coordinate care and establish contacts between the parties concerned. To identify potential intervention targets, this study deals with the challenges healthcare providers in general practice face in EoL care situations including patients, caregivers and networks. Methods: Focus group discussions with general practice teams in Germany were conducted to identify barriers to and enablers of an optimal support for family caregivers. Focus group discussions were analysed using content analysis. Results: Nineteen providers from 11 general practices took part in 4 focus group discussions. Participants identified challenges in communication with patients, caregivers and within the professional network. Communication with patients and caregivers focused on non-verbal messages, communicating at an appropriate time and perceiving patient and caregiver as a unit of care. Practice teams perceive themselves as an important part of the healthcare network, but also report difficulties in communication and cooperation with other healthcare providers. Conclusion: Healthcare providers in general practice identified relational challenges in daily primary palliative care with potential implications for EoL care. Communication and collaboration with patients, caregivers and among healthcare providers give opportunities for improving palliative care with a focus on the patient-caregiver dyad. It is insufficient to demand a (professional) support network; existing structures need to be recognized and included into the care

Recent developments in multiple sclerosis therapeutics

Multiple sclerosis, the most common neurologic disorder of young adults, is traditionally considered to be an inflammatory, autoimmune, demyelinating disease of the central nervous system. Based on this understanding, the initial therapeutic strategies were directed at immune modulation and inflammation control. These approaches, including high-dose corticosteroids for acute relapses and long-term use of parenteral interferon-β, glatiramer acetate or natalizumab for disease modification, are at best moderately effective. Growing evidence supports that, while an inflammatory pathology characterizes the early relapsing stage of multiple sclerosis, neurodegenerative pathology dominates the later progressive stage of the disease. Multiple sclerosis disease-modifying therapies currently in development attempt to specifically target the underlying pathology at each stage of the disease, while avoiding frequent self-injection. These include a variety of oral medications and monoclonal antibodies to reduce inflammation in relapsing multiple sclerosis and agents intended to promote neuroprotection and neurorepair in progressive multiple sclerosis. Although newer therapies for relapsing MS have the potential to be more effective and easier to administer than current therapies, they also carry greater risks. Effective treatments for progressive multiple sclerosis are still being sought