AADC deficiency from infancy to adulthood: Symptoms and developmental outcome in an international cohort of 63 patients

Aromatic l-amino acid decarboxylase deficiency (AADCD) is a rare, autosomal recessive neurodevelopmental disorder characterized by impaired synthesis of dopamine, noradrenaline, adrenaline and serotonin, leading to a complex syndrome of motor, behavioral, and autonomic symptoms. This retrospective study assessed the symptoms and developmental outcome of a large international cohort of patients with AADCD via physician and/or caregiver responses to a detailed, standardized questionnaire. Sixty-three patients (60% female; ages 6 months-36 years, median 7 years; 58 living) from 23 individual countries participated. Common symptoms at onset (median age 3 months, range 0-12 months) were hypotonia, developmental delay, and/or oculogyric crises. Oculogyric crises were present in 97% of patients aged 2 to 12 years, occurred in the majority of patients in all age groups, and tended to be most severe during early childhood. Prominent non-motor symptoms were sleep disturbance, irritable mood, and feeding difficulties. The majority of subjects (70%) had profound motor impairment characterized by absent head control and minimal voluntary movement, while 17% had mild motor impairment and were able to walk independently. Dopamine agonists were the medications most likely to produce some symptomatic benefit, but were associated with dose-limiting side effects (dyskinesia, insomnia, irritability, vomiting) that led to discontinuation 25% of the time. The age distribution of our cohort (70% of subjects under age 13 years) and the observation of a greater proportion of patients with a more severe disease phenotype in the younger compared to the older patients, both suggest a significant mortality risk during childhood for patients with severe disease

Tubular carbonate concretions as hydrocarbon migration pathways? Examples from North Island, New Zealand

Cold seep carbonate deposits are associated with the development on the sea floor of distinctive chemosyn¬thetic animal communities and carbonate minerali¬sation as a consequence of microbially mediated anaerobic oxidation of methane. Several possible sources of the methane exist, identifiable from the carbon isotope values of the carbonate precipitates. In the modern, seep carbonates can occur on the sea floor above petroleum reservoirs where an important origin can be from ascending thermogenic hydrocar¬bons. The character of geological structures marking the ascent pathways from deep in the subsurface to shallow subsurface levels are poorly understood, but one such structure resulting from focused fluid flow may be tubular carbonate concretions. Several mudrock-dominated Cenozoic (especially Miocene) sedimentary formations in the North Island of New Zealand include carbonate concretions having a wide range of tubular morphologies. The concretions are typically oriented at high angles to bedding, and often have a central conduit that is either empty or filled with late stage cements. Stable isotope analyses (δ13C, δ18O) suggest that the carbonate cements in the concretions precipitated mainly from ascending methane, likely sourced from a mixture of deep thermogenic and shallow biogenic sources. A clear link between the tubular concretions and overlying paleo-sea floor seep-carbonate deposits exists at some sites. We suggest that the tubular carbonate concretions mark the subsurface plumbing network of cold seep systems. When exposed and accessible in outcrop, they afford an opportunity to investigate the geochemical evolution of cold seeps, and possibly also the nature of linkages between subsurface and surface portions of such a system. Seep field development has implications for the characterisation of fluid flow in sedimentary basins, for the global carbon cycle, for exerting a biogeochemical influence on the development of marine communities, and for the evaluation of future hydrocarbon resources, recovery, and drilling and production hazards. These matters remain to be fully assessed within a petroleum systems framework for New Zealand’s Cenozoic sedimentary basins

Relationship between children's cognitions and later educational progress in rural South Africa:A longitudinal study

Background: Children in low and middle-income countries (LMIC) who remain in school have better health and employment outcomes. South Africa, like many LMIC, has a secondary school completion rate under 50%, leaving room for improvement if we can identify factors that affect educational attainment. This is the first longitudinal study to examine the effects of childhood mental health and cognitions on educational outcomes in LMIC. Methods: Using the Strengths and Difficulties Questionnaire (SDQ) and Cognitive Triad Inventory for Children (CTI-C), we assessed the psychological functioning and cognition of children aged 10-12 in rural South Africa. We linked that data with measures of educational progress collected five years later and examined associations between educational progress and 1) behavioural and emotional problems and 2) cognitive interpretations, adjusting for possible confounders. Results: Educational data was available for 443 individuals. 92% (n= 408) of individuals had advanced three or fewer grades in seven years. Having more positive cognitions (CTIC-C) was positively associated with progressing at least three grade levels (adjusted OR: 1.43; 95% CI: 1.14-1.79). There was no evidence for an association between emotional and behavioural problems (SDQ) and educational progress (OR: 0.90; 95% CI: 0.72-1.11). Conclusion: If children in LMIC can develop more positive perspectives, they may be able to stay in school longer. Cognitions can be modified, and future studies should test interventions that work to improve cognition in childhood, guided , for example, by principles of cognitive behavioral therapy

Making Good Tenure Decisions

This article provides information on decision making on the granting or denial of tenure to a faculty member. It not only has an effect on the professional life of a colleague, it has a major influence on the direction and long-term quality of the department. The tenure decision in made in the sixth year of a tenure-track faculty appointment. If a faculty member has been on the tenure track at two institutions, the years of service at the first institution usually count toward those six years, unless the faculty member and his of her current institution agree in writing at the time of appointment that they will not or that only a certain number of them will. The sooner the person is terminated or helped to find another position, the better for him or her and for the department

Follicular Delivery of Caffeine from a Shampoo for Hair Retention

A key factor in the prevention of hair loss is the provision of optimal conditions on the scalp. In this regard, reduction of oxidative stress on the scalp is one critical requirement to support the hair follicles to function optimally. Recently, a novel shampoo formulation technology containing anti-oxidants such as piroctone olamine has been demonstrated to improve hair retention based on micellar degradation and coacervation effects. Caffeine has also been shown to exhibit anti-oxidant activity including the ability to inhibit lipid peroxidation. As with piroctone olamine, it is expected that follicular delivery of caffeine will enhance its anti-oxidant activity in a region that will be beneficial for hair retention. In this study, two shampoo formulations as well as a control formulation were applied to the calf area of n = 9 male participants. The technique of differential tape stripping was applied to obtain the caffeine penetrated to the stratum corneum and to the hair follicles. Isotope-dilution liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was performed to demonstrate caffeine follicular delivery from the shampoo formulas. The results showed that the percentage of caffeine recovered in the hair follicles was 8–9% of the caffeine absorbed into the skin and matched an existing caffeine-based shampoo. In conclusion, a novel shampoo formulation technology has been developed that effectively delivers beneficial anti-oxidants to improve hair retention. This new shampoo is expected to be especially useful in the goal of retaining hair during aging

Advancing human capabilities for water security: A relational approach

We argue that a relational water security framework informed by the capabilities approach offers new ways to consider politics and cultures of water. Each dimension allows us to better contextualize water security beyond just an object (H2O) to be secured for a certain population. Instead, the relational perspective demands a fuller consideration of the political structures and processes through which water is secured, with emphasis on the social relations of access as opposed to simply the politics around water supply. We also attend to cultural dimensions, such as the meanings of water and customary practices that are not easily captured by standardized metrics. By including these dimensions, we necessarily broaden analytical space to evaluate water security as a relational and dynamic process tied to lived experience rather than as solely parameterized conditions in relation to access, quality, or availability of water. We first move to explain our broader conceptualization of water security as linked to human capabilities, then explore in more detail the specific engagements with politics and culture in the sections that follow

Autoantibodies to truncated GAD(96-585) antigen stratify risk of early insulin requirement in adult-onset diabetes

We investigated whether characterisation of full-length (f-)GADA responses could identify early insulin requirement in adult-onset diabetes. In 179 f-GADA positive participants diagnosed with type 2 diabetes, we assessed associations of truncated (t-)GADA positivity, f-GADA IgG subclasses, and f-GADA affinity with early insulin requirement (<5 years), type 1 diabetes genetic risk score (T1D GRS), and C-peptide. t-GADA positivity was lower in f-GADA positive without early insulin in comparison to f-GADA positive type 2 diabetes requiring insulin within 5 years, and type 1 diabetes (75% vs. 91% and 95% respectively, p<0.0001). t-GADA positivity (in those f-GADA positive) identified a group with a higher type 1 diabetes genetic susceptibility (mean T1D GRS 0.248 vs. 0.225, p=0.003), lower C-peptide (1156 pmol/L vs. 4289 pmol/L, p=1x10-7), and increased IA-2A positivity (23% vs. 6%, p=0.03). In survival analysis, t-GADA positivity was associated with early insulin requirement compared with those only positive for f-GADA, independently from age of diagnosis, f-GADA titre and duration of diabetes [adjusted HR 5.7 (95% CI 1.4, 23.5), p=0.017]. The testing of t-GADA in f-GADA positive individuals with type 2 diabetes identifies those who have genetic and clinical characteristics comparable to type 1 diabetes and stratifies those at higher risk of early insulin requirement

Projected early spread of COVID-19 in Africa through 1 June 2020.

For 45 African countries/territories already reporting COVID-19 cases before 23 March 2020, we estimate the dates of reporting 1,000 and 10,000 cases. Assuming early epidemic trends without interventions, all 45 were likely to exceed 1,000 confirmed cases by the end of April 2020, with most exceeding 10,000 a few weeks later