The basic income grant in Namibia: resource book

In recent months, the Basic Income Grant proposal has generated an overwhelming response in Namibia, and the launch of the Basic Income Grant Coalition has added further public debate. This resource book is compiled in order to inform policy makers and civil society role players about the background and the details of the proposal for a Basic Income Grant in Namibia. In addition, it provides the results of research of the social, economic and financial implications of a BIG in Namibia. The first section of the book documents the launch of the Basic Income Grant Coalition. The Council of Churches, the National Union of Namibian Workers, the National NGO Forum, the Namibian Network of AIDS Service Organisations, the Legal Assistance Centre, and the Labour, Resource and Research Institute committed themselves to the common platform on April 27th 2005. The platform of the coalition as well as the speeches at the launch of Bishop Dr. Z. Kameeta (Evangelical Lutheran Church in the Republic of Namibia (ELCRN) and Vice President of the Council of Churches in Namibia (CCN)), Mr. P. Naholo, Acting General Secretary of the National Union of Namibian Workers (NUNW), and Mr. S. Tjaronda, Chairperson of the Namibian NGO Forum (NANGOF), are published in this first section. This resource book is compiled in order to inform policy makers and civil society role players about the background and the details of the proposal for a Basic Income Grant in Namibia. The second section explains the underlying concept of the Basic Income Grant. Crucial questions of understanding and clarification are addressed in order to form the basis for an informed debate about the concept. The third section introduces the key passages of the findings and recommendations made by the Government appointed Namibia Tax Consortium (NAMTAX). In 2002 the tax consortium “found that by far the best method of addressing poverty and inequality would be a universal income grant [= Basic Income Grantf (NAMTAX, 2002:60). This research is crucial as it lays the foundation on the basis of which the churches, unions, NGOs and AIDS Service organisations have now formed the coalition to join hands with Government to see that this proposal can be implemented effectively. The fourth and fifth sections provide relevant results stemming from social and economic analysis. The fourth section by Dr. C. and Dr. D. Haarmann is based on a Microsimulation Model modelling the developmental impact of a Basic Income Grant on poverty and inequality. The fifth and final section by Prof. M. Samson and Ms. I. van Niekerk calculates the costs of the Basic Income Grant and its various financing options. Based on a comparative international Tax Effort Analysis, the affordability given Namibia’s current economic capacity is assessed. This section concludes by looking at likely second round effects on Namibia’s economy if a Basic Income Grant is to be introduced

The feasibility and acceptability of short-term, individual existential behavioural therapy for informal caregivers of patients recruited in a specialist palliative care unit

Background: Existential behavioural therapy ( EBT) is a recently developed intervention to support informal caregivers of patients in a specialist palliative care unit and was initially established as a six-session group programme. This pilot study aimed to test the feasibility and acceptability of an adapted short-term, individual approach of EBT in preparation for a randomized controlled trial ( RCT). Methods: The study was conducted in a prospective, mixed methods design including four quantitiative assessments with embedded qualitative interviews at one assessment. The intervention offered two one-hour therapeutic sessions focusing on ( 1) mindfulness and ( 2) existential meaning-in-life as a source of strength provided by a trained psychotherapist. To test the feasibility of the intervention, doubling of the participation rate, compared to the previous group study ( 13,6 %) as well as an attrition rate of less than 30 % were set as thresholds. To test the acceptability of the intervention, self-rated usefulness of individual aspects of the intervention and the frequency of implementing therapeutic elements by the carers were set as criteria. Acceptability testing also included the number of participants who completed both sessions, where we expected more than 75 % as a criterion for acceptability. Return rates of quantitative questionnaires were set as criteria for the feasibility of data collection (<33 % loss expected within the study period). Qualitative interviews were used to collect additional data on feasibililty and acceptability and to explore potential harms and benefits of the intervention. Results: 44/102 ( 43,1 %) of eligible informal caregivers agreed to participate in the study. Due to attrition of 13 caregivers ( attrition rate: 29,5 %), 31 caregivers were included in the trial. Self-rated usefulness showed sufficiant results for all but one individual aspect. Frequency of implementing therapeutic elements showed wide inter-item as well as inter-participant ranges and decreased over the study period. All participants completed both sessions. Return rates of the questionnaires were within the expected range. According to the interviews, the intervention was associated with several participant-identified benefits. No severe adverse effects were observed. Conclusions: Findings suggest that the short-term, individual EBT proved feasible and mostly acceptable

State-of-the-Art Automated Patch Clamp Devices: Heat Activation, Action Potentials, and High Throughput in Ion Channel Screening

Ion channels are essential in a wide range of cellular functions and their malfunction underlies many disease states making them important targets in drug discovery. The availability of standardized cell lines expressing ion channels of interest lead to the development of diverse automated patch clamp (APC) systems with high-throughput capabilities. These systems are now available for drug screening, but there are limitations in the application range. However, further development of existing devices and introduction of new systems widen the range of possible experiments and increase throughput. The addition of well controlled and fast solution exchange, temperature control and the availability of the current clamp mode are required to analyze standard cell lines and excitable cells such as stem cell-derived cardiomyocytes in a more physiologically relevant environment. Here we describe two systems with different areas of applications that meet the needs of drug discovery researchers and basic researchers alike. The here utilized medium throughput APC device is a planar patch clamp system capable of recording up to eight cells simultaneously. Features such as temperature control and recordings in the current clamp mode are described here. Standard cell lines and excitable cells such as stem cell-derived cardiomyocytes have been used in the voltage clamp and current clamp modes with the view to finding new drug candidates and safety testing methods in a more physiologically relevant environment. The high-throughput system used here is a planar patch clamp screening platform capable of recording from 96 cells in parallel and offers a throughput of 5000 data points per day. Full dose response curves can be acquired from individual cells reducing the cost per data point. The data provided reveals the suitability and relevance of both APC platforms for drug discovery, ion channel research, and safety testing

Effects of inserting fluorescent proteins into the α1S II–III loop: insights into excitation–contraction coupling

In skeletal muscle, intermolecular communication between the 1,4-dihydropyridine receptor (DHPR) and RYR1 is bidirectional: orthograde coupling (skeletal excitation–contraction coupling) is observed as depolarization-induced Ca2+ release via RYR1, and retrograde coupling is manifested by increased L-type Ca2+ current via DHPR. A critical domain (residues 720–765) of the DHPR α1S II–III loop plays an important but poorly understood role in bidirectional coupling with RYR1. In this study, we examine the consequences of fluorescent protein insertion into different positions within the α1S II–III loop. In four constructs, a cyan fluorescent protein (CFP)–yellow fluorescent protein (YFP) tandem was introduced in place of residues 672–685 (the peptide A region). All four constructs supported efficient bidirectional coupling as determined by the measurement of L-type current and myoplasmic Ca2+ transients. In contrast, insertion of a CFP–YFP tandem within the N-terminal portion of the critical domain (between residues 726 and 727) abolished bidirectional signaling. Bidirectional coupling was partially preserved when only a single YFP was inserted between residues 726 and 727. However, insertion of YFP near the C-terminal boundary of the critical domain (between residues 760 and 761) or in the conserved C-terminal portion of the α1S II–III loop (between residues 785 and 786) eliminated bidirectional coupling. None of the fluorescent protein insertions, even those that interfered with signaling, significantly altered membrane expression or targeting. Thus, bidirectional signaling is ablated by insertions at two different sites in the C-terminal portion of the α1S II–III loop. Significantly, our results indicate that the conserved portion of the α1S II–III loop C terminal to the critical domain plays an important role in bidirectional coupling either by conveying conformational changes to the critical domain from other regions of the DHPR or by serving as a site of interaction with other junctional proteins such as RYR1

The feasibility and acceptability of short-term, individual existential behavioural therapy for informal caregivers of patients recruited in a specialist palliative care unit

Background: Existential behavioural therapy ( EBT) is a recently developed intervention to support informal caregivers of patients in a specialist palliative care unit and was initially established as a six-session group programme. This pilot study aimed to test the feasibility and acceptability of an adapted short-term, individual approach of EBT in preparation for a randomized controlled trial ( RCT). Methods: The study was conducted in a prospective, mixed methods design including four quantitiative assessments with embedded qualitative interviews at one assessment. The intervention offered two one-hour therapeutic sessions focusing on ( 1) mindfulness and ( 2) existential meaning-in-life as a source of strength provided by a trained psychotherapist. To test the feasibility of the intervention, doubling of the participation rate, compared to the previous group study ( 13,6 %) as well as an attrition rate of less than 30 % were set as thresholds. To test the acceptability of the intervention, self-rated usefulness of individual aspects of the intervention and the frequency of implementing therapeutic elements by the carers were set as criteria. Acceptability testing also included the number of participants who completed both sessions, where we expected more than 75 % as a criterion for acceptability. Return rates of quantitative questionnaires were set as criteria for the feasibility of data collection (<33 % loss expected within the study period). Qualitative interviews were used to collect additional data on feasibililty and acceptability and to explore potential harms and benefits of the intervention. Results: 44/102 ( 43,1 %) of eligible informal caregivers agreed to participate in the study. Due to attrition of 13 caregivers ( attrition rate: 29,5 %), 31 caregivers were included in the trial. Self-rated usefulness showed sufficiant results for all but one individual aspect. Frequency of implementing therapeutic elements showed wide inter-item as well as inter-participant ranges and decreased over the study period. All participants completed both sessions. Return rates of the questionnaires were within the expected range. According to the interviews, the intervention was associated with several participant-identified benefits. No severe adverse effects were observed. Conclusions: Findings suggest that the short-term, individual EBT proved feasible and mostly acceptable

Oxidation and Reduction of Pig Skeletal Muscle Ryanodine Receptors

Time-dependent effects of cysteine modification were compared in skeletal ryanodine receptors (RyRs) from normal pigs and RyR(MH) (Arg615 to Cys615) from pigs susceptible to malignant hyperthermia, using the oxidizing reagents 4,4'-dithiodipyridine (4,4'-DTDP) and 5,5'-dithio-bis(2- nitrobenzoic acid) (DTNB) or the reducing agent dithiothreitol (DTT). Normal and RyR(MH) channels responded similarly to all reagents. DTNB (1 mM), either cytoplasmic (cis) or luminal (trans), or 1 mM 4,4'-DTDP (cis) activated RyRs, introducing an additional long open time constant. 4,4'-DTDP (cis), but not DTNB, inhibited channels after >5 min. Activation and inhibition were relieved by DTT (1-10 mM). DTT (10 mM, cytoplasmic or luminal), without oxidants, activated RyRs, and activation reversed with 1 mM DTNB. Control RyR activity was maintained with 1 mM DTNB and 10 mM DTT present on the same or opposite sides of the bilayer. We suggest that 1) 4,4'-DTDP and DTNB covalently modify RyRs by oxidizing activating or inhibiting thiol groups; 2) a modified thiol depresses mammalian skeletal RyR activity under control conditions; 3) both the activating thiols and the modified thiols, accessible from either cytoplasm or lumen, reside in the transmembrane region; 4) some cardiac sulfhydryls are unavailable in skeletal RyRs; and 5) Cys615 in RyR(MH) is functionally unimportant in redox cycling

How Many Cysteine Residues Regulate Ryanodine Receptor Channel Activity

RyRs contain 80-100 cysteine residues per subunit, of which ~25% are free for covalent modification, while the remainder are either modified or form intraprotein disulfides. Oxidizing and nitrosylating reagents have several effects on single RyR channel activity, which depend on the type of modifying reagent, the isoform of the RyR, and ligands bound to the channel. We present evidence here for four major classes of functional cysteine residues associated with RyR channels, i.e., two classes with free -SH groups that either activate or inhibit channels when covalently modified and two classes, with endogenous modification, that either inhibit or activate. Single-channel characteristics provide evidence for four discrete responses within the first activating class, two responses within the second inhibiting class and two types of response within the third endogenously modified class. All but one of these changes in channel properties depend on residues located on the cytoplasmic or membrane-associated domains of the RyR; the remaining response is confined to the luminal domain. If it is assumed that each type of response depends on a separate subclass of cysteine residue and that each subclass contains a minimum of one cysteine per subunit, our results suggest that there are at least nine cysteine residues per subunit with functional connections to the gating mechanism of RyR channels. These cysteine residues may be selectively modified under physiological and pathological conditions to regulate Ca2+ release from the sarcoplasmic reticulum and contraction