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In this Review (Part I), we investigate the scientific evidence that multiple sclerosis (MS) is caused by the death of oligodendrocytes, the cells that synthesize myelin, due to a lack of biochemical and nutritional factors involved in mitochondrial energy production in these cells. In MS, damage to the myelin sheaths surrounding nerve axons causes disruption of signal transmission from the brain to peripheral organs, which may lead to disability. However, the extent of disability is not deterred by the use of MS medication, which is based on the autoimmune hypothesis of MS. Rather, disability is associated with the loss of brain volume, which is related to the loss of grey and white matter. A pathology-supported genetic testing (PSGT) method, developed for personalized assessment and treatment to prevent brain volume loss and disability progression in MS is discussed. This involves identification of MS-related pathogenic pathways underpinned by genetic variation and lifestyle risk factors that may converge into biochemical abnormalities associated with adverse expanded disability status scale (EDSS) outcomes and magnetic resonance imaging (MRI) findings during patient follow-up. A Metabolic Model is presented which hypothesizes that disability may be prevented or reversed when oligodendrocytes are protected by nutritional reserve. Evidence for the validity of the Metabolic Model may be evaluated in consecutive test cases following the PSGT method. In Part II of this Review, two cases are presented that describe the PSGT procedures and the clinical outcomes of these individuals diagnosed with MS.

In Part I of this Review we evaluated the scientific evidence for a Metabolic Model of multiple sclerosis (MS). Part II outlines the implementation of an adaptive pathology-supported genetic testing (PSGT) algorithm aimed at preventing/reversing disability in two illustrative MS cases, starting with a questionnaire-based risk assessment, including family history and lifestyle factors. Measurement of iron, vitamin B12, vitamin D, cholesterol and homocysteine levels identified biochemical deficits in both cases. Case 1, after following the PSGT program for 15 years, had an expanded disability status scale (EDSS) of 2.0 (no neurological sequelae) together with preserved brain volume on magnetic resonance imaging (MRI). A novel form of iron deficiency was identified in Case 1, as biochemical testing at each hospital submission due to MS symptoms showed low serum iron, ferritin and transferrin saturation, while hematological status and erythrocyte sedimentation rate measurement of systemic inflammation remained normal. Case 2 was unable to walk unaided until her EDSS improved from 6.5 to 4.0 over 12 months after implementation of the PSGT program, with amelioration of her suboptimal biochemical markers and changes to her diet and lifestyle, allowing her to regain independence. Genotype-phenotype correlation using a pathway panel of functional single nucleotide variants (SNVs) to facilitate clinical interpretation of whole exome sequencing (WES), elucidated the underlying metabolic pathways related to the biochemical deficits. A cure for MS will remain an elusive goal if separated from nutritional support required for production and maintenance of myelin, which can only be achieved by a lifelong investment in wellness.

This paper reports the results of an investigation of thermal cycles and microstructural development in 5182-H111 aluminium alloy during low speed (0.2 m/min) and high speed (1.5 m/min) friction stir welding (FSW), using quenched pin-break specimens. The results show that welds made at both speeds have excellent mechanical properties, although these derive from different thermomechanical mechanisms. For the low speed weld thermal conductivity plays the most significant role in the development of microstructure, while in the case of high speed welding it is the high strain rate plastic deformation that is the dominant mechanism. The yield strength in the stir zone of both the 0.2 m/min and 1.5 m/min welds could be explained through the Hall–Petch relationship, leading to an observable increase in the case of the 1.5 m/min weld. By contrast, an increase in yield strength beneath the shoulder of the 1.5 m/min weld was driven by strain hardening.

Background Antipsychotic polypharmacy ("polypharmacy") is the concurrent prescribing of more than one antipsychotic. It is widely practised, as reported in the literature, and is known to increase the risk of adverse outcomes for patients. Objective To quantify the prevalence and magnitude of polypharmacy in patients with schizophrenia or schizoaffective disorder and identify potential factors contributing to this practice. Setting Armadale Mental Health Service (a public inpatient and outpatient psychiatric facility in Perth, Western Australia). Method A retrospective, cross-sectional study was conducted, evaluating the medical records of adult (18-64 years old) patients fulfilling the established inclusion criteria in the period between August and December 2016. Data collected included the number and doses of antipsychotic(s) prescribed and documented rationale for polypharmacy. Defined daily doses and proportions of maximum licensed daily doses were calculated for all regularly prescribed antipsychotics and were evaluated as measures of antipsychotic load. Main Outcome Measure The percentage prevalence of antipsychotic polypharmacy; defined daily antipsychotic doses and proportions of maximum licensed daily doses. Results Seventy-seven patients were assessed, with a polypharmacy prevalence of 39.0%. Total defined daily doses ranged from 0.9 to 5.9 and maximum licensed daily doses from 0.4 to 2.3. Documented rationales for polypharmacy included poor symptom control, patient's preference, hesitancy to amend other prescribers' management plans, off-label antipsychotic indications and medication cross-titration. Conclusion Antipsychotic polypharmacy occurred in more than one-third of patients. Individual antipsychotics were typically prescribed at doses within the licensed range, however, the total proportion of combined maximum licensed doses and combined daily defined doses often exceeded 100%. Due to suboptimal documentation, prescribing rationale was unclear in the majority of cases. The magnitude of polypharmacy aims to foster a greater appreciation of the prescribed antipsychotic load, increasing clinician self-awareness of prescribing practices and facilitating future opportunities to optimise prescribing.

Globally, universities make use of peer physical examination (PPE) in health professions students’ teaching of physical examination skills. PPE has many educational benefits, such as teaching normal anatomy and function, development of compassion and empathy, to feel what it is like to be examined from a patient’s perspective, improvement of communication skills, correcting errors in technique and improve confidence. The benefits for patients include protection from repeated examinations by unskilled students. The aim of the study was to investigate health sciences students’ perceptions of the ethical aspects of PPE. A qualitative investigation, which included two focus group interviews with students and one with lecturers, was used for data collection. Most students and lecturers regarded PPE as beneficial, as it provides a safe environment for students in the health sciences to improve their clinical competence and confidence, without fear of embarrassment or failure. Students stated that PPE promoted the development of empathy with and respect for their patients. It was suggested that in a culturally diverse society, guidelines specifically related to religious customs and convictions should be provided to give students an indication of appropriate and acceptable behaviour towards fellow students when practising PPE. The use of PPE in the training of students in the health professions should support the ethical principles of Beauchamp and Childress, namely beneficence, non-maleficence, autonomy and justice/fairness.

Background Ethical reasoning informs decision making and professional judgement, is guided by codes of ethics and conduct, and requires navigation through a regulatory framework. Ethical reasoning should evolve throughout the pharmacy internship year and prepare interns for independent practice. Objective To explore the ethical reasoning and processes of Australian pharmacists and pharmacy interns. Setting Queensland community pharmacists and interns. Method A survey to determine use of resources to guide ethical decisions, management of ethical dilemmas, and exposure to potential practice privacy breaches. Participants were recruited at pharmacy intern training events, a pharmacist education session and through telephone contact of randomised community pharmacies. Main outcome measure Comparison between pharmacist and intern responses using 5-point Likert scales, listings and prioritising. Results In total 218 completed surveys were analysed: 121 pharmacy interns and 97 pharmacists. The Code of Ethics was identified as the resource most frequently consulted when faced with ethical dilemmas. Interns were more likely to consult legislation and regulatory authorities whereas pharmacists with colleagues. Responses to ethical vignette scenarios and exposure to privacy breaches varied between interns and pharmacists, with some scenarios revealing significant differences. Most participants had been exposed to a variety of potential privacy breaches in practice. Conclusion Interns focussed on legislation and guidelines when presented with hypothetical ethical dilemmas. In contrast to this positivist approach, pharmacists reported using a social constructionist approach with peers as a reference. Pharmacists avoided ethical scenario options that required complex management. Interns reported more exposure to potential practice privacy breaches.

E-textbooks are often considered as having several advantages over printed textbooks. However, research shows conflicting results regarding school learners’ satisfaction with e-textbooks. In South Africa a particular e-book platform, EduBook for e-textbooks, is currently used in 170 schools across the country. In this study the satisfaction and continuance intention of 10 learners from a South African high school where cross-subject implementation of the EduBook platform was piloted, were considered. In this mixed method study, a control group of 7 non e-textbooks users from other schools were used to compare the findings. Guided by the adapted ECM model of Baker-Eveleth and Stone (2015), quantitative data was collected through eye tracking tests and qualitative data was collected through individual interviews and a focus group discussion. The findings confirm the influence of usability, expectations and perceived usefulness on satisfaction and continuance intention to use the e-textbook platform. In addition, it highlights post-adoption expectations created by cross-subject implementation and its influence on learners’ satisfaction. The important role played by the way in which teachers use the platform is emphasised and learners provided useful suggestions on how teachers can be prepared and assisted in the use of the platform.

Background Practising pharmacists continuously develop their ethical reasoning skills, which evolve with practice experience and exposure to challenging scenarios. Considering the recent expansion of the roles of pharmacists and the paradigm shift in pharmacy practice, it is timely to explore community pharmacists' attitudes regarding the importance of ethics and their ethical reasoning. Objective To explore underlying factors influencing community pharmacists' and pharmacy students' ethical reasoning and attitudes towards pharmacy ethics, ethical reasoning processes and perceived current dilemmas. Setting Practising registered community pharmacists, pharmacists with provisional registration (interns) and final year pharmacy students in Australia. Method Two focus group discussions and two interviews were conducted with 16 Western Australian community pharmacists, interns and students. Participants were purposively selected for gender, background, practice setting, and practice experience. Main outcome measure Emerging themes embracing important influences on community pharmacists', interns' and students' ethical reasoning and perceived current ethical dilemmas and challenges. Results Two major themes embraced participants' ethical reasoning processes and conduct: (1) fundamental underpinning, from personal values and practice exposure, and (2) paradigm influenced, such as the changing healthcare landscape, expansion of roles, management of dilemmas, and competence. Increased frequency and complexity of ethical dilemmas related to role expansion. Rural pharmacists experienced unique ethical dilemmas in relation to practice isolation, privacy and confidentiality. Conclusion Changes in the community pharmacy practice environment has increasingly exposed pharmacists to more complex ethical dilemmas. Pharmacists practising in rural communities experience unique challenges. Structured and sound ethical reasoning skills are essential as pharmacists are faced with contemporary challenges.

Elsinoe punicae was shown to be responsible for a new disease on pomegranates in South Africa. This disease has been found in three of the pomegranate production areas in the Cape provinces, and is characterised by scab-like symptoms on the fruit and brown spots on the leaves. Representative isolates were characterised by morphology, cultural growth and sequencing of the ITS. Additionally, the LSU, rpb2 and TEF1-α gene regions were also sequenced for one representative isolate from pomegranate. Phylogenetic analyses of the four loci confirmed the isolates as E. punicae. RAPD analyses were also performed with three primers on 19 isolates of E. punicae. The analyses showed that E. punicae isolates clustered together with high support apart from the reference isolates of E. australis, E. fawcetti and E. australis pathotype jojoba. Pathogenicity tests were conducted with E. punicae and two reference isolates (E. australis, E. fawcetti - Citrus pathogens) on whole plant leaves and detached leaves of pomegranate and different citrus types [grapefruit, rough lemon, navels, Valencias and mandarins] in official quarantine facilities. The results confirmed E. punicae as a pathogen of pomegranate and not citrus.

The relatively new severe plastic deformation method, friction stir processing (FSP), is a cutting-edge process to synthesize surface and bulk metal matrix composites. The present work is focused to produce Cu/TiC copper matrix composites (CMCs) and investigate the microstructure and sliding wear behavior at room temperature without lubrication. In the beginning of the process, TiC particulates were pressed in a machined groove on the surface of copper plates. The dimensions of the groove were altered to produce four different volume fractions of TiC particulates (0, 6, 12, and 18 vol%). FSP was accomplished by an optimized set of process parameters. The microstructure was observed using optical microscopy, scanning electron microscopy, and electron back-scattered diffraction. The microstructures showed a consistent dispersion of TiC particulates in the copper matrix irrespective of the volume fraction. The dispersion was observed to be uniform across the whole stir zone region. The interfacial bonding with the copper was proper. The reinforcement of TiC particulates enhanced the microhardness and led to a reduction in the wear rate of the composite remarkably. TiC particulates changed the wear mechanism and the geometry of wear debris. Highest hardness and lowest wear rate were observed in Cu/18 vol% TiC CMC.

Multiple sclerosis (MS) is a disorder related to myelin damage, which can be investigated by neuroimaging techniques such as fractional anisotropy (FA), a measure of microstructural white matter properties. The objectives of this study were to investigate (1) the relationship between FA and disability using an extremes of outcome approach, and (2) whether blood iron parameters were associated with FA and/or disability. Patients diagnosed with MS (n = 107; 14 males and 93 females) had iron parameter tests and disability determinations using the Expanded Disability Status Scale (EDSS). FA was recorded in 48 white matter tracts in 11 of the female patients with MS and 12 female controls. Results: In patients with high disability scores the mean FA was significantly lower (0.34 ± 0.067) than in the control group (0.45 ± 0.036; p = 0.04), while patients with low disability had mean FA values (0.44 ± 0.014) similar to controls (p = 0.5). Positive associations were found between FA and the iron parameters serum iron, ferritin and percentage transferrin saturation (%Tfsat) in all the white matter tracts. For % Tfsat, the associations were highly significant in 14 tracts (p

The global distribution of citrus black spot (CBS) disease, caused by Phyllosticta citricarpa, is climatically constrained, which is evident from its occurrence in citrus growing areas with warm, summer rainfall and its absence from areas with cooler, Mediterranean-type winter rainfall. Various epidemiological and modelling studies have supported this observation, predominantly estimating unsuitability for P. citricarpa in Mediterranean type climates, with no more than marginal suitability estimated at a few localities within some regions with Mediterranean type climates. The study by Martinez-Minaya et al. (European Journal of Plant Pathology, 143, 69–83, 2015), describes an historic sequence of recorded CBS occurrence in parts of South Africa, conducts an autocorrelation analysis and a correlative analysis with Koppen-Geiger climate zones and makes observations about the occurrence of certain Koppen-Geiger climate zones in the European Union. The study suggests that significant portions of the European Union and the broader Mediterranean basin are climatically similar to warm, summer rainfall areas in South Africa where P. citricarpa persists and causes CBS disease and concludes that the potential distribution of P. citricarpa is less constrained by climatic factors than spatial contagion. However, in this critique we expose methodological shortcomings in the Martinez-Minaya et al. (European Journal of Plant Pathology, 143, 69–83, 2015) study and conclude that the study grossly overestimated the extent of the geographical area that could support P. citricarpa, thereby rendering the findings scientifically unreliable.

This study describes the process undertaken to develop, implement and evaluate a simulation-based training package focused on medication management and reconciliation processes for final year pharmacy students about a patient’s hospital journey. A five module training package was developed following a literature review and consultation with stakeholders. The simulation-based package immersed students in a real-life scenario and was delivered to final year pharmacy students over a six-week period in 2016. Data on knowledge, skills and confidence was collected via a survey in the week preceding engagement with the online training package and 1 week post completion of the training. The mean score was compared across four student categories: three categories incorporated students who had not completed a hospital pharmacy placement and one category comprised students who had completed a hospital placement. Qualitative feedback was collected via an online survey at the conclusion of the training program. Of the 79 participants, 44 (55.7%) completed both the pre and post- test surveys that showed the change in score was statistically significant. There was a significant positive change in mean test scores across all four student categories for the domains of skills, knowledge and confidence. Assessment of students’ confidence according to 16 ranking statements also improved markedly post-training. Thirty-one students provided qualitative feedback that was generally positive. The positive outcomes reinforce the rationale to include online simulation-based methodologies as part of pharmacy education programs. The model provides a reproducible framework for online simulated learning activities that could be applied within various professions and educational environments.

The induced path number $$\rho (G)$$?(G) of a graph G is defined as the minimum number of subsets into which the vertex set of G can be partitioned so that each subset induces a path. A product Nordhaus---Gaddum-type result is a bound on the product of a parameter of a graph and its complement. Hattingh et al. (Util Math 94:275---285, 2014) showed that if G is a graph of order n, then $$\lceil \frac{n}{4} \rceil \le \rho (G) \rho (\overline{G}) \le n \lceil \frac{n}{2} \rceil $$?n4?≤?(G)?(G¯)≤n?n2?, where these bounds are best possible. It was also noted that the upper bound is achieved when either G or $$\overline{G}$$G¯ is a graph consisting of n isolated vertices. In this paper, we determine best possible upper and lower bounds for $$\rho (G) \rho (\overline{G})$$?(G)?(G¯) when either both G and $$\overline{G}$$G¯ are connected or neither G nor $$\overline{G}$$G¯ has isolated vertices.

South Africa is one of the largest ferrochromium (FeCr) producers. Most FeCr is exported to developed countries. Therefore the impact of this industry is of national and international importance. Cr(VI) and conductivity of surface water in four case study areas, near five FeCr smelters were monitored for approximately 1 year. Results indicated that FeCr production in three case study areas had a negative influence on the Cr(VI) concentration and/or the conductivity of surface waters. In the remaining case study areas, drinking water, originating from groundwater, was severely polluted with Cr(VI). The main factors causing pollution were surface run-off and/or seepage, while atmospheric deposition did not seem to contribute significantly. The extinction of diatoms during a severe Cr(VI) surface water pollution event (concentrations up to 216 lg/L) in one of the case study areas was also observed, which clearly indicates the ecological impact of such surface water pollution events http://link.springer.com/article/10.1007/s11663-015-0395-x DOI: 10.1007/s11663-015-0395-x

The discovery of the exotic fruit fly pest Bactrocera dorsalis (Diptera: Tephritidae), previously recognized as Bactrocera invadens, on the African continent in 2003 raised biosecurity concerns in South Africa where agriculture is of major socio-economic importance. This prompted the development of a nationally coordinated system to prevent introduction of this pest into the country. A steering committee was constituted to provide a platform for multi-stakeholder cooperation. A national action plan on B. dorsalis was developed. A surveillance network was initiated to provide for early detection of B. dorsalis. The first B. dorsalis eradication campaign was launched in 2010 following the detection of the pest in the northern border region of South Africa. Multiple point incursions were detected thereafter in the northern parts of the country and for the first 2 years all of these were considered successfully eradicated. However, the rate and geographic spread of incursions increased over time. In March 2013 the pest was declared present in the Vhembe district, Limpopo Province. All areas affected by B. dorsalis were placed under quarantine and eradication actions are still ongoing in areas other than the Vhembe district. The national control strategy on B. dorsalis continues to be focussed on preventing further incursions, slowing the spread of the pest and monitoring the extent of its distribution within South Africa.

A Late Pleistocene hominin tracksite has been identified in coastal aeolianite rocks on the Cape south coast of South Africa, an area of great significance for the emergence of modern humans. The tracks are in the form of natural casts and occur on the ceiling and side walls of a ten-metre long cave. Preservation of tracks is of variable quality. Up to forty hominin tracks are evident. Up to thirty-five hominin tracks occur on a single bedding plane, with potential for the exposure of further tracks. Five tracks are apparent on a second hominin track-bearing bedding plane. A number of individuals made the tracks while moving down a dune surface. A geological investigation at the site and stratigraphic comparison to published geochronological studies from this area suggest that the tracks are ~90 ka in age. If this is the case, the shoreline at the time would have been approximately 2 km distant. This is the first reported hominin tracksite from this time period. It adds to the relatively sparse global record of early hominin tracks, and represents the largest and best preserved archive of Late Pleistocene hominin tracks found to date. The tracks were probably made by Homo sapiens.

Let $$G=(V,E)$$G=(V,E) be a graph. A set $$S\subseteq V$$S⊆V is a restrained dominating set if every vertex in $$V-S$$V-S is adjacent to a vertex in $$S$$S and to a vertex in $$V-S$$V-S. The restrained domination number of $$G$$G, denoted $$\gamma _{r}(G)$$?r(G), is the smallest cardinality of a restrained dominating set of $$G$$G. The best possible upper bound $$q(n,k)$$q(n,k) is established in Joubert (Discrete Appl Math 161:829---837, 2013) on the size $$m(G)$$m(G) of a graph $$G$$G with a given order $$n \ge 5$$n?5 and restrained domination number $$k \in \{3, \ldots , n-2\}$$k?{3,?,n-2}. We extend this result to include the cases $$k=1,2,n$$k=1,2,n, and characterize graphs $$G$$G of order $$n \ge 1$$n?1 and restrained domination number $$k \in \{1,\dots , n-2,n\}$$k?{1,?,n-2,n} for which $$m(G)=q(n,k)$$m(G)=q(n,k).