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Supervision has been identified as an important factor in the success of postgraduate students, even as the most significant variable and a large number of studies have been conducted to identify factors that contribute to supervision success. However the dependent variable in these studies--supervision success--has been an elusive one to define. The aim of this article is to investigate one aspect of supervision success, namely throughput success. We isolate two factors (gender and home language) pertaining to the student profile and one factor (multiplicity) pertaining to supervision practice and then investigate the association between the factors and throughput success. Multiplicity is a term defined here to distinguish the practice of solo supervision (one supervisor) from that of having co-supervision. The methodology includes both quantitative and qualitative strategies with a survey and interviews as the data capturing methods. The main contribution is to highlight the impact of multiplicity on throughput success. This research should be of interest to researchers, supervisors and academic planners. (Contains 6 tables and 2 figures.)

A three-dimensional proton treatment planning system called PROXELPLAN has been used at the National Accelerator Centre (NAC) since October 1994. This system is entirely based on the VOXELPLAN planning system, developed at the Deutches Krebsforschungszentrum (DKFZ), Heidelberg, Germany. The VOXELPLAN system provides the treatment planning infrastructure while the proton dose distributions are calculated using a software module that was initially developed at the Royal Marsden Hospital, UK. The proton module has been extensively modified and refined. It uses a rayline-tracing algorithm which is suitable for planning current treatments but is not sufficiently dynamic to accommodate the use of compensators. A sophisticated pencil beam algorithm is currently under development. [ABSTRACT FROM AUTHOR]

The 200 MeV cyclotron facility at the National Accelerator Centre has been operational since 1987. Between September 1988 and December 1997 a total of 973 patients (26,916 fields) had been treated on the 66 MeV p+Be isocentric neutron therapy system. Patients are currently being treated according to several protocols, including tumors of the head and neck, salivary gland and breast and soft tissue sarcomas, uterine sarcomas and paranasal sinuses. A multiblade post-collimator trimmer has recently being installed. This device provides improved neutron beam shaping capability. Between September 1993 and December 1997 a total of 243 patients (4008 fields) had been treated (mainly intracranial stereotactic irradiations) on the fixed horizontal 200 MeV proton therapy facility. The facility incorporates an innovative automatic patient positioning system. Two new fixed beam lines for proton therapy are presently being designed (horizontal and 30 degrees to the vertical) for an existing unused treatment vault. Spot scanning systems will be developed for both beam lines. [ABSTRACT FROM AUTHOR]

There is a growing international trend towards the protection of freshwater resources from pollution by imposing instream guidelines and specified waste-discharge conditions. Current methods for devising freshwater quality guidelines are based on species sensitivity distributions (SSDs) that are used to identify pollutant concentrations, ensuring the protection of a modelled percentage of species (95% protection is a common goal). SSDs are derived from the toxicity test results of as many taxa as possible for each polluting substance. Waste-discharge licences can be for single substances, specified in terms of chemical concentrations, and derived in conjunction with instream guidelines; or for complex mixtures, specified in terms of toxic units. In both cases toxicity test results are the core data used. The emphasis on SSDs calls into question the species constituting the test populations. It is likely that SSDs based in part on the responses of local organisms will achieve superior site-specific ecological protection. Until the early 1990s, there were very few data on the tolerances of South African freshwater organisms. In the intervening decade, the Unilever Centre for Environmental Water Quality at Rhodes University has developed a toxicity database that, to date, records the responses of 21 South African freshwater taxa to 26 single-substance pollutants or mixtures. This is the most comprehensive database of South African toxicity responses available and has been used in the drawing up of methods and guidelines to protect water resources. This paper aims to make these data available and to describe applications of the data using selected case studies. [ABSTRACT FROM AUTHOR]

Proton therapy is of great interest to pediatric cancer patients because of its optimal depth dose distribution. In view of healthy tissue damage and the increased risk of secondary cancers, we investigated DNA damage induction and repair of radiosensitive hematopoietic stem and progenitor cells (HSPCs) exposed to therapeutic proton and photon irradiation due to their role in radiation-induced leukemia. Human CD34 + HSPCs were exposed to 6 MV X-rays, mid- and distal spread-out Bragg peak (SOBP) protons at doses ranging from 0.5 to 2 Gy. Persistent chromosomal damage was assessed with the micronucleus assay, while DNA damage induction and repair were analyzed with the γ-H2AX foci assay. No differences were found in induction and disappearance of γ-H2AX foci between 6 MV X-rays, mid- and distal SOBP protons at 1 Gy. A significantly higher number of micronuclei was found for distal SOBP protons compared to 6 MV X-rays and mid- SOBP protons at 0.5 and 1 Gy, while no significant differences in micronuclei were found at 2 Gy. In HSPCs, mid-SOBP protons are as damaging as conventional X-rays. Distal SOBP protons showed a higher number of micronuclei in HSPCs depending on the radiation dose, indicating possible changes of the in vivo biological response., (© 2023. Springer Nature Limited.)

Objective: To update the state of the art regarding the acquisition of spinal high-velocity low-amplitude psychomotor skills competency among chiropractors and chiropractic students., Methods: Available electronic articles from 5 databases, published between June 2015 and August 2020, were obtained. Eligible studies underwent methodological quality assessments using the Joanna Briggs Institute Critical Appraisal Checklists and Cochrane Collaboration's Risk of Bias Tools., Results: Fourteen critically appraised studies were identified, including 10 cohort studies and 4 randomized controlled trials. There was no literature excluded due to high risk of bias. The type of augmented devices included a mannequin on a force platform, a computer-connected device, a human analogue mannequin, and a 3-dimensional electrogoniometer with an instrumented spatial linkage., Conclusion: The use of augmented feedback devices such as human analogue mannequins with force-sensing table technology and computer-connected devices is potentially beneficial in the chiropractic curricula and may facilitate student learning and improvement of spinal manipulation. More studies are required to determine whether psychomotor skill aids translate directly into raised competency levels in novice clinicians., (© 2023 Association of Chiropractic Colleges.)

The radiosensitivity of haematopoietic stem and progenitor cells (HSPCs) to neutron radiation remains largely underexplored, notwithstanding their potential role as target cells for radiation-induced leukemogenesis. New insights are required for radiation protection purposes, particularly for aviation, space missions, nuclear accidents and even particle therapy. In this study, HSPCs (CD34 + CD38 + cells) were isolated from umbilical cord blood and irradiated with 60 Co γ-rays (photons) and high energy p(66)/Be(40) neutrons. At 2 h post-irradiation, a significantly higher number of 1.28 ± 0.12 γ-H2AX foci/cell was observed after 0.5 Gy neutrons compared to 0.84 ± 0.14 foci/cell for photons, but this decreased to similar levels for both radiation qualities after 18 h. However, a significant difference in late apoptosis was observed with Annexin-V + /PI + assay between photon and neutron irradiation at 18 h, 43.17 ± 6.10% versus 55.55 ± 4.87%, respectively. A significant increase in MN frequency was observed after both 0.5 and 1 Gy neutron irradiation compared to photons illustrating higher levels of neutron-induced cytogenetic damage, while there was no difference in the nuclear division index between both radiation qualities. The results point towards a higher induction of DNA damage after neutron irradiation in HSPCs followed by error-prone DNA repair, which contributes to genomic instability and a higher risk of leukemogenesis., (© 2021. The Author(s).)

Background: Tuberculosis remains a global health challenge, with early diagnosis key to its reduction. Face-mask sampling detects exhaled Mycobacterium tuberculosis. We aimed to investigate bacillary output from patients with pulmonary tuberculosis and to assess the potential of face-mask sampling as a diagnostic method in active case-finding., Methods: We did a 24-h longitudinal study in patients from three hospitals in Pretoria, South Africa, with microbiologically confirmed pulmonary tuberculosis. Patients underwent 1 h of face-mask sampling eight times over a 24-h period, with contemporaneous sputum sampling. M tuberculosis was detected by quantitative PCR. We also did an active case-finding pilot study in inhabitants of an informal settlement near Pretoria. We enrolled individuals with symptoms of tuberculosis on the WHO screening questionnaire. Participants provided sputum and face-mask samples that were tested with the molecular assay Xpert MTB/RIF Ultra. Sputum-negative and face-mask-positive individuals were followed up prospectively for 20 weeks by bronchoscopy, PET-CT, and further sputum analysis to validate the diagnosis., Findings: Between Sept 22, 2015, and Dec 3, 2015, 78 patients with pulmonary tuberculosis were screened for the longitudinal study, of whom 24 completed the study (20 had HIV co-infection). M tuberculosis was detected in 166 (86%) of 192 face-mask samples and 38 (21%) of 184 assessable sputum samples obtained over a 24-h period. Exhaled M tuberculosis output showed no diurnal pattern and did not associate with cough frequency, sputum bacillary content, or chest radiographic disease severity. On May 16, 2018, 45 individuals were screened for the prospective active case-finding pilot study, of whom 20 had tuberculosis symptoms and were willing to take part. Eight participants were diagnosed prospectively with pulmonary tuberculosis, of whom six were exclusively face-mask positive at screening. Four of these participants (three of whom were HIV-positive) had normal findings on chest radiography but had treatment-responsive early tuberculosis-compatible lesions on PET-CT scans, with Xpert-positive sputum samples after 6 weeks., Interpretation: Face-mask sampling offers a highly efficient and non-invasive method for detecting exhaled M tuberculosis, informing the presence of active infection both with greater consistency and at an earlier disease stage than with sputum samples. The approach shows potential for diagnosis and screening, particularly in difficult-to-reach communities., Funding: Wellcome Trust, CARA (Council for At-Risk Academics), University of Leicester, the UK Medical Research Council, and the National Institute for Health Research. VIDEO ABSTRACT., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The lack of information on how biological systems respond to low-dose and low dose-rate exposures makes it difficult to accurately assess the carcinogenic risks. This is of critical importance to space radiation, which remains a serious concern for long-term manned space exploration. In this study, the γ-H2AX foci assay was used to follow DNA double-strand break (DSB) induction and repair following exposure to neutron irradiation, which is produced as secondary radiation in the space environment. Human lymphocytes were exposed to high dose-rate (HDR: 0.400 Gy/min) and low dose-rate (LDR: 0.015 Gy/min) p (66)/Be(40) neutrons. DNA DSB induction was investigated 30 min post exposure to neutron doses ranging from 0.125 to 2 Gy. Repair kinetics was studied at different time points after a 1 Gy neutron dose. Our results indicated that γ-H2AX foci formation was 40% higher at HDR exposure compared to LDR exposure. The maximum γ-H2AX foci levels decreased gradually to 1.65 ± 0.64 foci/cell (LDR) and 1.29 ± 0.45 (HDR) at 24 h postirradiation, remaining significantly higher than background levels. This illustrates a significant effect of dose rate on neutron-induced DNA damage. While no significant difference was observed in residual DNA damage after 24 h, the DSB repair half-life of LDR exposure was slower than that of HDR exposure. The results give a first indication that the dose rate should be taken into account for cancer risk estimations related to neutrons.

In the last 40 years only one new antitubercular drug has been approved, whilst resistance to current drugs, including rifampicin, is spreading. Here, we used the model organism Mycobacterium smegmatis to study mechanisms of phenotypic mycobacterial resistance, employing quantitative mass spectrometry-based proteomics to investigate the temporal effects of sub-lethal concentrations of rifampicin on the mycobacterial proteome at time-points corresponding to early response, onset of bacteriostasis and early recovery. Across 18 samples, a total of 3,218 proteins were identified from 31,846 distinct peptides averaging 16,250 identified peptides per sample. We found evidence that two component signal transduction systems (e.g. MprA/MprB) play a major role during initial mycobacterial adaptive responses to sub-lethal rifampicin and that, after dampening an initial SOS response, the bacteria supress the DevR (DosR) regulon and also upregulate their transcriptional and translational machineries. Furthermore, we found a co-ordinated dysregulation in haeme and mycobactin synthesis. Finally, gradual upregulation of the M. smegmatis-specific rifampin ADP-ribosyl transferase was observed which, together with upregulation of transcriptional and translational machinery, likely explains recovery of normal growth. Overall, our data indicates that in mycobacteria, sub-lethal rifampicin triggers a concerted phenotypic response that contrasts significantly with that observed at higher antimicrobial doses.

The Mycobacterium tuberculosis bacillus has a number of unique features that make it a particularly effective human pathogen. Although genomic analysis has added to our current understanding of the molecular basis by which M. tuberculosis damages its host, proteomics may be better suited to describe the dynamic interactions between mycobacterial and host systems that underpin this disease. The M. tuberculosis proteome has been investigated using proteomics for over a decade, with increasingly sophisticated mass spectrometry technology and sensitive methods for comparative proteomic profiling. Deeper coverage of the M. tuberculosis proteome has led to the identification of hundreds of putative virulence determinants, as well as an unsurpassed coverage of post-translational modifications. Proteomics is therefore uniquely poised to contribute to our understanding of this pathogen, which may ultimately lead to better management of the disease.

Background and Purpose: To evaluate the outcome of malignant salivary gland tumours treated with neutron therapy to assess the potential for other high linear energy transfer (LET) beams., Materials and Methods: Neutrons at iThemba LABS are produced by the reaction of 66MeV protons on a beryllium target. A median dose 20.4Gy, in 12 fractions in 4weeks or 15 fractions in 5weeks, was given to 335 patients with 176 irresectable, 104 macroscopically residual and 55 unresected tumours., Results: Locoregional control was 60.6% at 5years and 39.1% at 10years and DSS was 66.8% and 53.7% at 5 and 10years respectively. In the univariate analysis T4, >4cm, high grade, squamous carcinoma, unresected and irresectable tumours, and positive nodes were significantly worse for LRC. In the multivariate analysis tumours >6cm, squamous carcinoma, irresectable tumours and nodes were significantly worse for LRC. Tumours >6cm, high grade, squamous carcinoma and nodes were significantly worse for DSS. Neither LRC nor DSS was influenced by age, sex, site, dose, fractionation or for initial or recurrent disease., Conclusions: Neutron therapy appears to be the treatment of choice for macroscopically incompletely excised and irresectable salivary gland tumours with improved survival rates. Further improvement may be achieved with other high LET modalities with a superior dose profile, such as carbon ions., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Tuberculosis (TB) remains a major cause of illness and death worldwide, making a new TB vaccine an urgent public health priority. Purified protein derivative (PPD)-negative adults (n = 50) were equally randomized to receive 3 doses at 1-month intervals (at 0, 1, and 2 months) of one of the following vaccines: Mtb72F/AS02(A) (10 or 40 μg antigen), Mtb72F/saline (10 or 40 μg antigen), or AS02(A). Mtb72F/AS02(A) recipients received an additional dose 1 year after the first dose to evaluate if the elicited immune response could be boosted. Mtb72F/AS02(A) vaccines were locally reactogenic but clinically well tolerated, with transient adverse events (usually lasting between 1 and 4 days) that resolved without sequelae being observed. No vaccine-related serious adverse events were reported. Vaccination with Mtb72F/AS02(A) induced a strong Mtb72F-specific humoral response and a robust Mtb72F-specific CD4(+) T-cell response, both of which persisted at 9 months after primary immunization and for 1 year after the booster immunization. There was no significant difference between the magnitude of the CD4(+) T-cell response induced by the 10-μg and 40-μg Mtb72F/AS02(A) vaccines. The Mtb72F-specific CD4(+) T cells predominantly expressed CD40L; CD40L and interleukin-2 (IL-2); CD40L and tumor necrosis factor alpha (TNF-α); CD40L, IL-2, and TNF-α; and CD40L, IL-2, TNF-α, and gamma interferon (IFN-γ). Serum IFN-γ, but not TNF-α, was detected 1 day after doses 2 and 3 for the Mtb72F/AS02(A) vaccine but did not persist. Vaccine-induced CD8(+) T-cell responses were not detected, and no immune responses were elicited with AS02(A) alone. In conclusion, Mtb72F/AS02(A) is clinically well tolerated and is highly immunogenic in TB-naïve adults. The 10- and 40-μg Mtb72F/AS02(A) vaccines show comparable safety and immunogenicity profiles.

Tuberculosis (TB) remains uncontrolled in many parts of the world and the development of an effective vaccine against TB represents a high priority unmet medical need. Healthy PPD (tuberculin purified protein derivative)-negative adult volunteers, aged 18-40 years received three doses of the candidate Mtb72F/AS02A vaccine according to a 0-1-2 months schedule in an open-label Phase I study (NCT00730795). Solicited, unsolicited and serious adverse events (AEs), hematological and biochemical laboratory parameters were assessed. Mtb72F-specific humoral responses were assessed by ELISA and cell-mediated immune (CMI) responses by intracellular cytokine staining (ICS) and short-term ELISPOT assays. CMI responses to the component peptides (Mtb39a and the Mtb32a C- and N-terminal antigen domains, Mtb32C and Mtb32N) were also assessed by ICS. The Mtb72F/AS02A vaccine appeared to be mainly locally reactogenic but this was considered acceptable, since these AEs were usually transient and resolved within 1-2 days. Most AEs reported were mild in intensity, no serious AEs occurred, no medically significant biochemical or hematological abnormalities related to vaccination were measured and all AEs resolved without sequelae. The vaccine induced statistically significant changes in humoral and CMI response measures. The Mtb72F antigen induced good production of IL-2 and IFNgamma in the ELISPOT assay and CD4(+) T cells expressing at least two activation markers (mainly CD40-L and IL-2) were observed with ICS. A similar CMI profile was observed with Mtb39a and Mtb32N. The induced CMI responses persisted for at least 6 months post-vaccination. All subjects were seropositive for anti-Mtb72F antibodies one month post-dose 2 and 6 months post-dose 3. This first trial in humans found Mtb72F/AS02A to have an acceptable tolerability, to be immunogenic in healthy adults and warrants further development of the vaccine.

We report the first safety and immunogenicity trial of the Plasmodium falciparum vaccine candidate FMP2.1/AS02A, a recombinant E. coli-expressed protein based upon the apical membrane antigen-1 (AMA-1) of the 3D7 clone formulated with the AS02A adjuvant. We conducted an open-label, staggered-start, dose-escalating Phase I trial in 23 malaria-naïve volunteers who received 8, 20 or 40microg of FMP2.1 in a fixed volume of 0.5mL of AS02A on a 0, 1, and 2 month schedule. Nineteen of 23 volunteers received all three scheduled immunizations. The most frequent solicited local and systemic adverse events associated with immunization were injection site pain (68%) and headache (29%). There were no significant laboratory abnormalities or vaccine-related serious adverse events. All volunteers seroconverted after second immunization as determined by ELISA. Immune sera recognized sporozoites and merozoites by immunofluorescence assay (IFA), and exhibited both growth inhibition and processing inhibition activity against homologous (3D7) asexual stage parasites. Post-immunization, peripheral blood mononuculear cells exhibited FMP2.1-specific lymphoproliferation and IFN-gamma and IL-5 ELISPOT assay responses. This is the first PfAMA-1-based vaccine shown to elicit both potent humoral and cellular immunity in humans. Encouraged by the potential of FMP1/AS02A to target host immunity against PfAMA-1 that is known to be expressed by sporozoite, hepatic and erythrocytic stages, we have initiated field trials of FMP2.1/AS02A in an endemic population in the Republic of Mali.