1,271 research outputs found
The family law act 1996 in context
Full details of the published version of the book can be viewed at the link below. This chapter is available here with the permission of the publishers
Changing divorce
Full details of the published version of the book can be viewed at the link below. This chapter is available here with the permission of the publishers
The development of a classification system for inland aquatic ecosystems in South Africa
A classification system is described that was developed for inland aquatic ecosystems in South Africa, including wetlands. The six-tiered classification system is based on a top-down, hierarchical classification of aquatic ecosystems, following the functionally-oriented hydrogeomorphic (HGM) approach to classification but incorporating structural attributes at the lower levels of the hierarchy. At Level 1, a distinction is made between inland, estuarine and shallow marine systems using the degree of connectivity to the open ocean as the key discriminator. Inland systems are characterised by the complete absence of marine exchange and/or tidal influence. At Level 2, inland systems are grouped according to the most appropriate spatial framework for the particular application. At Level 3, four primary Landscape Units are distinguished (Valley floor, Slope, Plain, Bench) on the basis of the topographic position within which a particular inland aquatic ecosystem is situated, in recognition of the influence that the landscape setting has over hydrological and hydrodynamic processes acting within an aquatic ecosystem. Level 4 identifies HGM Units, defined primarily according to landform, hydrological characteristics and hydrodynamics. The following primary HGM Units (or HGM Types), which represent the main units of analysis for the classification system, are distinguished at Level 4A: (1) River; (2) Floodplain Wetland; (3) Channelled Valley-Bottom Wetland; (4) Unchannelled Valley-Bottom Wetland; (5) Depression; (6) Seep; (7) Wetland Flat. Secondary discriminators are applied at Level 5 to classify the hydrological regime of an HGM Unit, and Descriptors at Level 6 to categorise a range of biophysical attributes. The HGM Unit at Level 4 and the Hydrological Regime at Level 5 together constitute a Functional Unit, which represents the focal point of the classification system. The utility of the classification system is ultimately dependent on the level to which ecosystem units are classified, which is in turn constrained by the type and extent of information available.Keywords: freshwater ecosystems, hydrogeomorphic (HGM) units, inland water ecosystems, wetlands, wetland classification syste
Timed inhibition of CDC7 increases CRISPR-Cas9 mediated templated repair.
Repair of double strand DNA breaks (DSBs) can result in gene disruption or gene modification via homology directed repair (HDR) from donor DNA. Altering cellular responses to DSBs may rebalance editing outcomes towards HDR and away from other repair outcomes. Here, we utilize a pooled CRISPR screen to define host cell involvement in HDR between a Cas9 DSB and a plasmid double stranded donor DNA (dsDonor). We find that the Fanconi Anemia (FA) pathway is required for dsDonor HDR and that other genes act to repress HDR. Small molecule inhibition of one of these repressors, CDC7, by XL413 and other inhibitors increases the efficiency of HDR by up to 3.5 fold in many contexts, including primary T cells. XL413 stimulates HDR during a reversible slowing of S-phase that is unexplored for Cas9-induced HDR. We anticipate that XL413 and other such rationally developed inhibitors will be useful tools for gene modification
Prolonged dopamine signalling in striatum signals proximity and value of distant rewards
Predictions about future rewarding events have a powerful influence on behaviour. The phasic spike activity of dopamine-containing neurons, and corresponding dopamine transients in the striatum, are thought to underlie these predictions, encoding positive and negative reward prediction errors. However, many behaviours are directed towards distant goals, for which transient signals may fail to provide sustained drive. Here we report an extended mode of reward-predictive dopamine signalling in the striatum that emerged as rats moved towards distant goals. These dopamine signals, which were detected with fast-scan cyclic voltammetry (FSCV), gradually increased or—in rare instances—decreased as the animals navigated mazes to reach remote rewards, rather than having phasic or steady tonic profiles. These dopamine increases (ramps) scaled flexibly with both the distance and size of the rewards. During learning, these dopamine signals showed spatial preferences for goals in different locations and readily changed in magnitude to reflect changing values of the distant rewards. Such prolonged dopamine signalling could provide sustained motivational drive, a control mechanism that may be important for normal behaviour and that can be impaired in a range of neurologic and neuropsychiatric disorders.National Institutes of Health (U.S.) (Grant R01 MH060379)National Parkinson Foundation (U.S.)Cure Huntington’s Disease Initiative, Inc. (Grant A-5552)Stanley H. and Sheila G. Sydney Fun
A Single-Arm, Proof-Of-Concept Trial of Lopimune (Lopinavir/Ritonavir) as a Treatment for HPV-Related Pre-Invasive Cervical Disease
BACKGROUND:
Cervical cancer is the most common female malignancy in the developing nations and the third most common cancer in women globally. An effective, inexpensive and self-applied topical treatment would be an ideal solution for treatment of screen-detected, pre-invasive cervical disease in low resource settings.
METHODS:
Between 01/03/2013 and 01/08/2013, women attending Kenyatta National Hospital's Family Planning and Gynaecology Outpatients clinics were tested for HIV, HPV (Cervista®) and liquid based cervical cytology (LBC -ThinPrep®). HIV negative women diagnosed as high-risk HPV positive with high grade squamous intraepithelial lesions (HSIL) were examined by colposcopy and given a 2 week course of 1 capsule of Lopimune (CIPLA) twice daily, to be self-applied as a vaginal pessary. Colposcopy, HPV testing and LBC were repeated at 4 and 12 weeks post-start of treatment with a final punch biopsy at 3 months for histology. Primary outcome measures were acceptability of treatment with efficacy as a secondary consideration.
RESULTS:
A total of 23 women with HSIL were treated with Lopimune during which time no adverse reactions were reported. A maximum concentration of 10 ng/ml of lopinavir was detected in patient plasma 1 week after starting treatment. HPV was no longer detected in 12/23 (52.2%, 95%CI: 30.6-73.2%). Post-treatment cytology at 12 weeks on women with HSIL, showed 14/22 (63.6%, 95%CI: 40.6-82.8%) had no dysplasia and 4/22 (18.2%, 95%CI: 9.9-65.1%) were now low grade demonstrating a combined positive response in 81.8% of women of which 77.8% was confirmed by histology. These data are supported by colposcopic images, which show regression of cervical lesions.
CONCLUSIONS:
These results demonstrate the potential of Lopimune as a self-applied therapy for HPV infection and related cervical lesions. Since there were no serious adverse events or detectable post-treatment morbidity, this study indicates that further trials are clearly justified to define optimal regimes and the overall benefit of this therapy.
TRIAL REGISTRATION:
ISRCTN Registry 48776874
Dynamic Crystallization Pathways of Polymorphic Pharmaceuticals Revealed in Segmented Flow with Inline Powder X-ray Diffraction
Understanding the transitions between polymorphs is essential in the development of strategies for manufacturing and maximizing the efficiency of pharmaceuticals. However, this can be extremely challenging: crystallization can be influenced by subtle changes in environment, such as temperature and mixing intensity or even imperfections in the crystallizer walls. Here, we highlight the importance of in situ measurements in understanding crystallization mechanisms, where a segmented flow crystallizer was used to study the crystallization of the pharmaceuticals urea: barbituric acid (UBA) and carbamazepine (CBZ). The reactor provides highly reproducible reaction conditions, while in situ synchrotron powder X-ray diffraction (PXRD) enables us to monitor the evolution of this system. UBA has two polymorphs of almost equivalent free-energy and so is typically obtained as a polymorphic mixture. In situ PXRD analysis uncovered a progression of polymorphs from UBA III to the thermodynamic polymorph UBA I, where different positions along the length of the tubular flow crystallizer correspond to different reaction times. Addition of UBA I seed crystals modified this pathway such that only UBA I was observed throughout, while transformation from UBA III into UBA I still occurred in the presence of UBA III seeds. Information regarding the mixing-dependent kinetics of the CBZ form II to III transformation was also uncovered in a series of seeded and unseeded flow crystallization runs, despite atypical habit expression. These results illustrate the importance of coupling controlled reaction environments with in situ XRD to study the phase relationships in polymorphic materials
Demographic and circumstantial accounts of burn mortality in Cape Town, South Africa, 2001-2004: An observational register based study
<p>Abstract</p> <p>Background</p> <p>Burns are a persisting public health problem in low- and middle-income countries; however, epidemiologic data for these settings is scarce. South Africa is no exception although there is an emerging knowledge base, especially for paediatric burns. The current study describes the epidemiology of burn mortality across the lifespan in Cape Town (2.9 million inhabitants in 2001), one of the six South African metropolitan centres.</p> <p>Methods</p> <p>The distribution of burn mortality across socio-demographic groups and also their circumstances of occurrence were investigated using four year (2001 to 2004) surveillance data from the National Injury Mortality Surveillance System (n = 1024 cases).</p> <p>Results</p> <p>Burn mortality occurred at a rate of 7.9 per 100 000 person-years (95% CI: 7.3-8.3). Males sustained fatal rates 2.2 times more than that for females (p < 0.001), with rates significantly higher in the 25 to 38 and 39 to 50 age groups than at other ages (p < 0.001). The greatest difference between male and female deaths was observed in the 25 to 38 year age group, when almost three male deaths occurred for every female one. The vast majority of fatal burns were registered as accidental and occurred in the home, either over the cold and wet months or during recreational periods over weekends and across the year. Alcohol intoxication was reported for the majority of those adults whose alcohol blood levels were tested (i.e. 52.6% of cases aged 16+ years).</p> <p>Conclusion</p> <p>Besides paediatric burns, the high prevalence and circumstances of occurrence of burns among middle age men are a source of concern. There are reasons to believe that this over-representation is a reflection of detrimental living conditions, life-style and poor socio-economic status. It is recommended that there be greater prioritisation of prevention activities that involve the control or management of kerosene heat sources, the provision of alternatives to flammable housing materials, and the implementation of strategies to reduce harmful drinking practices.</p
Spirituality as an Essential Determinant for the Good Life, its Importance Relative to Self-Determinant Psychological Needs
This study focuses on the relevance of spirituality as an essential element for the Good Life. Despite spirituality’s prominence in people’s lives and cultures, it has been mostly neglected in psychological needs theories. This paper investigates the value of spirituality compared to that of the three basic psychological needs of self-determination theory: relatedness, competence and autonomy. In a scenario study design, participants in two samples (students and train passengers) were asked to judge a survey on the personal well-being of an imaginary person. The results show that spirituality positively contributes to the qualification of a good life, in terms of desirability and moral goodness. In addition, the crucial role of relatedness was confirmed
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