Psychosocial challenges of children with disabilities in Sekhukhune District, Limpopo province of South Africa: Towards a responsive integrated disability strategy.

Background: Disability, and everything it encompasses, presents major challenges to individuals, families and communities worldwide. Children with disabilities (CWD) are marginalised and excluded in most societies. Discrimination and prejudice towards CWD are compounded by poverty, lack of essential services and support and sometimes a hostile and inaccessible environment. Objectives: The study sought to examine the psychosocial challenges experienced by CWD in the Sekhukhune district of Limpopo province, South Africa. Based on the identified, articulated and expressed challenges, the study sought to recommend improvement of the existing Integrated National Disability Strategy (INDS) for greater responsiveness to the needs of CWD at both provincial and local levels. Method: The interpretivist qualitative mode of enquiry was the chosen methodology for this study. Phenomenology and descriptive research designs guided the study. Purposive sampling was employed, and data were collected from 36 participants using three triangulated methods: individual in-depth interviews, focus group discussions and key informant interviews. Thematic data analysis was used to analyse data. Results: The findings revealed that CWD in Sekhukhune experienced numerous challenges which affected their social functioning, development and general well-being. Aggravating factors included stigma, labelling and discrimination; disability-specific discrimination and bullying; exclusive education; sexual exploitation; lack of governmental support and poor implementation of disability-specific policies, amongst others. Conclusion: The provisions of the INDS to promote inclusion, integration, mainstreaming and equitable access to resources and services remained an ideal rather than a reality for CWD in Sekhukhune.

Direct observation of ultrafast exciton localization in an organic semiconductor with soft X-ray transient absorption spectroscopy.

The localization dynamics of excitons in organic semiconductors influence the efficiency of charge transfer and separation in these materials. Here we apply time-resolved X-ray absorption spectroscopy to track photoinduced dynamics of a paradigmatic crystalline conjugated polymer: poly(3-hexylthiophene) (P3HT) commonly used in solar cell devices. The π→π* transition, the first step of solar energy conversion, is pumped with a 15 fs optical pulse and the dynamics are probed by an attosecond soft X-ray pulse at the carbon K-edge. We observe X-ray spectroscopic signatures of the initially hot excitonic state, indicating that it is delocalized over multiple polymer chains. This undergoes a rapid evolution on a sub 50 fs timescale which can be directly associated with cooling and localization to form either a localized exciton or polaron pair.

Psychosocial challenges of children with disabilities in Sekhukhune District, Limpopo province of South Africa: Towards a responsive integrated disability strategy

Disability, and everything it encompasses, presents major challenges to individuals, families and communities worldwide. Children with disabilities (CWD) are marginalised and excluded in most societies. Discrimination and prejudice towards CWD are compounded by poverty, lack of essential services and support and sometimes a hostile and inaccessible environment. Objectives: The study sought to examine the psychosocial challenges experienced by CWD in the Sekhukhune district of Limpopo province, South Africa. Based on the identified, articulated and expressed challenges, the study sought to recommend improvement of the existing Integrated National Disability Strategy (INDS) for greater responsiveness to the needs of CWD at both provincial and local levels. Method: The interpretivist qualitative mode of enquiry was the chosen methodology for this study. Phenomenology and descriptive research designs guided the study. Purposive sampling was employed, and data were collected from 36 participants using three triangulated methods: individual in-depth interviews, focus group discussions and key informant interviews. Thematic data analysis was used to analyze data. Results: The findings revealed that CWD in Sekhukhune experienced numerous challenges which affected their social functioning, development and general well-being. Aggravating factors included stigma, labelling and discrimination; disability-specific discrimination and bullying; exclusive education; sexual exploitation; lack of governmental support and poor implementation of disability-specific policies, amongst others. Conclusion: The provisions of the INDS to promote inclusion, integration, mainstreaming and equitable access to resources and services remained an ideal rather than a reality for CWD in Sekhukhune.

Dual PARP and RAD51 Inhibitory Drug Conjugates Show Synergistic and Selective Effects on Breast Cancer Cells.

The genetic principle of synthetic lethality has most successfully been exploited in therapies engaging Poly-ADP-ribose-polymerase (PARP) inhibitors to treat patients with homologous recombination (HR)-defective tumors. In this work, we went a step further following the idea of a local molecular cooperation and designed hybrid compounds M1-M3. The drug conjugates M1-M3 combine Olaparib, the first PARP inhibitor approved for clinical use, with Cpd 1, an inhibitor of RAD51 that blocks its HR functions and yet permits RAD51 nucleoprotein filament formation on single-stranded DNA. While in M2 and M3, the parental drugs are linked by -CO-(CH2)n-CO-spacers (n = 2 and 4, respectively), they are directly merged omitting the piperazine ring of Olaparib in M1. Monitoring anti-survival effects of M1-M3 in six breast cancer cell lines of different molecular subtypes showed that in each cell line, at least one of the drug conjugates decreased viability by one to two orders of magnitude compared with parental drugs. While triple-negative breast cancer (TNBC) cells with frequent BRCA1 pathway dysfunction were sensitive to spacer-linked hybrid compounds M1 and M2 regardless of their HR capacities, non-TNBC cells were responsive to the merged drug conjugate M1 only, suggesting different spatial requirements for dual inhibition in these two groups of cell lines. These results demonstrate that, depending on chemical linkage, dual PARP1-RAD51 inhibitory drugs can either sensitize non-TNBC and re-sensitize TNBC cells, or discriminate between these groups of cells.

Does the application of Opsite⋄ Flexigrid⋄ occlude the oxygen saturation readings in healthy individuals using the moorVMS-OXY machine?

BACKGROUND: A proportion of people who have been diagnosed with peripheral arterial disease and diabetes mellitus will be susceptible to chronic wounds. Oxygen is vital for wound healing, so oxygen measurements should to be taken as predictive values for wound healing in patients. When measuring oxygen at the wound bed, there is potentially a risk of cross-infection if no protective barrier is used; and skin stripping if an adhesive barrier is used on the wound bed. This cross sectional within subject repeated measures pilot study, aims to determine if the application of opsite film, as an infection control measure, in one or two layers, impacts on tissue oxygenation readings obtained when using the MoorVMS-OXY. METHODS: Mean oxygen saturation percentages were measured from 29 limbs of 18 healthy participants. Oxygen saturation was measured for 20 s and analysed at the first metatarsophalangeal joint using no film, one and two layers using the MoorVMS-OXY. A one-way repeated ANOVA with a Bonferroni post hoc test was performed to test for statistically significant differences between the values of the three parameters and multiple pairwise comparisons was completed. RESULTS: Amongst the three layers, there was a statistically significant difference in oxygen saturation between the two layers of Opsite Flexigrid and none; and also between the two layers of Flexigrid and single layer (p < 0.05). It was also established that there was no statistically significant difference between the single layer of Opsite Flexigrid and no Flexigrid layer (p > 0.05). CONCLUSIONS: The results imply that one layer of Opsite Flexigrid is a suitable protective barrier to use when establishing capillary bed oxygen perfusion with the MoorVMS-OXY. However, the application of two Opsite Flexigrid layers, to prevent skin stripping, decreases the recorded values of oxygen saturation percentages significantly, therefore providing inaccurate results. Indicating that a double layer cannot be used over ulceration sites if measuring oxygen levels at the wound bed.

Toward indicators of the performance of US Infrastructures under climate change risks.

Built infrastructures are increasingly disrupted by climate-related extreme events. Being able to monitor what climate change implies for US infrastructures is of considerable importance to all levels of decision-makers. A capacity to develop cross-cutting, widely applicable indicators for more than a dozen different kinds of infrastructure, however, is severely limited at present. The development of such indicators must be considered an ongoing activity that will require expansion and refinement. A number of recent consensus reports suggest four priorities for indicators that portray the impacts of climate change, climate-related extreme events, and other driving forces on infrastructure. These are changes in the reliability of infrastructure services and the implications for costs; changes in the resilience of infrastructures to climate and other stresses; impacts due to the interdependencies of infrastructures; and ongoing adaptation in infrastructures.

Dynamics of secondary contamination from the interaction of high-power laser pulses with metal particles attached on the input surface of optical components.

We investigate the interaction of 355-nm and 1064-nm nanosecond laser pulses with nominally spherical metallic particles dispersed on the input surface of transparent substrates or high-reflectivity (HR) multilayer dielectric coatings, respectively. The objective is to elucidate the interaction mechanisms associated with contaminant-induced degradation and damage of transparent and reflective optical elements for high-power laser systems. The experiments involve time-resolved imaging capturing the dynamics of the interaction pathway, which includes plasma formation, particle ejection, and secondary contamination by droplets originating from the liquefied layer of the particle. The results suggest that HR coatings are more susceptible to secondary contamination by liquid droplets produced by the particles because of the different geometry of excitation and the location of plasma initiation. Modeling results focus on better understanding the melting of the particle surface, leading to ejections of liquid droplets and the pressure applied to the substrate, leading to mechanical damage.

Randomized Comparison of Hypochlorous Acid With 5% Sulfamylon Solution as Topical Therapy Following Skin Grafting.

Objective: Infections are a serious complication of thermal injury. Excision and grafting have led to a decrease in incidence, but to ensure successful skin grafting, antimicrobial irrigants are frequently utilized to prevent infection. A safe, efficacious, and cost-effective irrigant capable of preventing infections would be a valuable adjunctive therapy. The objectives of this study were to determine whether the test article was noninferior to current therapy in controlling infection and reducing postoperative pain in patients with skin graft. Methods: Patients with burns requiring skin grafting were randomized to hypochlorous acid or 5% Sulfamylon solution as topical dressings postoperatively. Inclusion criteria included thermal injury 20% or more total body surface area requiring excision and autografting, and age 18 years or more. Exclusion criteria included pregnant females, chlorine sensitivity, and electrical/chemical/cold injuries. The following outcomes were assessed: patient demographics, graft viability, infection, pain score, narcotic usage, adverse events, and cost. Results: Treatment groups were demographically equivalent. There were no differences in adverse or serious adverse events between the 2 groups. Graft viability and infection rate were equivalent between the 2 groups. In addition, pain scores and narcotic usage were similar. Hypochlorous acid was significantly less expensive than 5% Sulfamylon solution. Conclusions: Hypochlorous acid demonstrated equivalent efficacy and safety compared with 5% Sulfamylon when used as the postoperative topical dressing for skin grafts. Hypochlorous acid was more cost-effective. This pilot study was limited by its small sample size. However, hypochlorous acid shows promise as a topical wound dressing and further study with larger groups is warranted.

Femtosecond Laser Filaments for Use in Sub-Diffraction-Limited Imaging and Remote Sensing.

Probing remote matter with laser light is a ubiquitous technique used in circumstances as diverse as laser-induced breakdown spectroscopy and barcode scanners. In classical optics, the intensity that can be brought to bear on a remote target is limited by the spot size of the laser at the distance of the target. This spot size has a lower bound determined by the diffraction limit of classical optics. However, amplified femtosecond laser pulses generate intensity sufficient to modify the refractive index of the ambient air and undergo self-focusing. This self-focusing effect leads to the generation of highly intense laser filaments which maintain their intensity and small sub-millimeter diameter size at distances well beyond the classical Rayleigh length. Such intensity provides the capability of remote scanning, imaging, sensing, and spectroscopy with enhanced spatial resolution. We describe a technique for generating filaments with a femtosecond regenerative chirped-pulse amplifier, and for using the resulting filament to conduct imaging and spectroscopic measurements at remote distances of at least several meters.

The professionalism of psychiatry registrars as perceived by patients and various health practitioners at Weskoppies Psychiatric Hospital, Pretoria.

OBJECTIVES: Amidst calls for improved professionalism, this study examined the professionalism of psychiatry registrars at Weskoppies Hospital as evaluated by their patients, themselves, their consultants and other health practitioners. The second objective was to examine the perceived importance of aspects of professionalism and compare these descriptively among the various health practitioners and patients. METHOD: Participants completed the Professionalism Mini-Evaluation Exercise Questionnaire in evaluating the professionalism of the registrar. The number of questionnaires completed by patients, allied health practitioners, consultant psychiatrists and psychiatry registrars were, respectively, 100, 50, 25 and 20; thus, 195 in total. This previously validated questionnaire consists of 21 items that enquire about doctor-patient relationship skills, reflective skills, time management and interprofessional relationship skills. Participants also ranked the three items of the questionnaire that they considered most important. RESULTS: Highly statistically significant differences among four groups emerged for both the total and all four subscale scores, with patients generally rating the professionalism of registrars as lower, and not meeting with expectations. All four groups ranked 'listened actively to patient' and 'showed interest in patient as person' highly. Patients and allied health practitioners ranked the attribute 'was on time' highly, while consultants and registrars did not. CONCLUSION: Improving professionalism requires that the attributes 'listening actively to patient' and 'recognising and meeting patient needs' are taken seriously. Doing so requires that patients also evaluate the professionalism of registrars, rather than relying merely on the evaluation by consultants as being sufficient.

Development of a hydrogen cyanide inhalation exposure system and determination of the inhaled median lethal dose in the swine model.

OBJECTIVE: Cyanide is a highly toxic chemical, and acute exposure depletes cells and tissue of oxygen, depressing the respiratory, cardiovascular and neurological systems and potentially leading to death. Cyanide has been used as a weapon since ancient Rome and continues to pose a potential threat today. A well-characterized animal model is necessary for the development of novel methods of rapid detection and treatment. This manuscript describes the development of an inhalation exposure system designed to evaluate the lethality of acute cyanide inhalation in the porcine model. MATERIALS AND METHODS: A custom designed hydrogen cyanide (HCN) inhalation exposure system provided stable cyanide concentrations to un-anesthetized swine while monitoring respiratory parameters. Real-time respiratory monitoring, cyanide concentration and body weight were used to calculate inhaled doses. RESULTS: The inhalation exposure system generated controlled HCN ranging from 260 to 986 ppm to achieve inhaled doses between 1.78 and 3.97 mg/kg. Based on survival outcomes, the median lethal dose was determined to be 2.21 mg/kg, and the median lethal exposure level was 5893 mg min/m3. DISCUSSION: The ability of the HCN inhalation exposure system to deliver target inhaled doses and the determination of the inhaled median lethal dose in swine support the use of the exposure system and animal model for the evaluation of medical countermeasures of acute inhaled HCN toxicity.

The professionalism of psychiatry registrars as perceived by patients and various health practitioners at Weskoppies Psychiatric Hospital, Pretoria

Objectives: Amidst calls for improved professionalism, this study examined the professionalism of psychiatry registrars at Weskoppies Hospital as evaluated by their patients, themselves, their consultants and other health practitioners. The second objective was to examine the perceived importance of aspects of professionalism and compare these descriptively among the various health practitioners and patients. Method: Participants completed the Professionalism Mini-Evaluation Exercise Questionnaire in evaluating the professionalism of the registrar. The number of questionnaires completed by patients, allied health practitioners, consultant psychiatrists and psychiatry registrars were, respectively, 100, 50, 25 and 20; thus, 195 in total. This previously validated questionnaire consists of 21 items that enquire about doctor-patient relationship skills, reflective skills, time management and interprofessional relationship skills. Participants also ranked the three items of the questionnaire that they considered most important. Results: Highly statistically significant differences among four groups emerged for both the total and all four subscale scores, with patients generally rating the professionalism of registrars as lower, and not meeting with expectations. All four groups ranked 'listened actively to patient' and 'showed interest in patient as person' highly. Patients and allied health practitioners ranked the attribute 'was on time' highly, while consultants and registrars did not. Conclusion: Improving professionalism requires that the attributes 'listening actively to patient' and 'recognising and meeting patient needs' are taken seriously. Doing so requires that patients also evaluate the professionalism of registrars, rather than relying merely on the evaluation by consultants as being sufficien

Particle damage sources for fused silica optics and their mitigation on high energy laser systems.

High energy laser systems are ultimately limited by laser-induced damage to their critical components. This is especially true of damage to critical fused silica optics, which grows rapidly upon exposure to additional laser pulses. Much progress has been made in eliminating damage precursors in as-processed fused silica optics (the advanced mitigation process, AMP3), and very high damage resistance has been demonstrated in laboratory studies. However, the full potential of these improvements has not yet been realized in actual laser systems. In this work, we explore the importance of additional damage sources-in particular, particle contamination-for fused silica optics fielded in a high-performance laser environment, the National Ignition Facility (NIF) laser system. We demonstrate that the most dangerous sources of particle contamination in a system-level environment are laser-driven particle sources. In the specific case of the NIF laser, we have identified the two important particle sources which account for nearly all the damage observed on AMP3 optics during full laser operation and present mitigations for these particle sources. Finally, with the elimination of these laser-driven particle sources, we demonstrate essentially damage free operation of AMP3 fused silica for ten large optics (a total of 12,000 cm2 of beam area) for shots from 8.6 J/cm2 to 9.5 J/cm2 of 351 nm light (3 ns Gaussian pulse shapes). Potentially many other pulsed high energy laser systems have similar particle sources, and given the insight provided by this study, their identification and elimination should be possible. The mitigations demonstrated here are currently being employed for all large UV silica optics on the National Ignition Facility.

Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis: Subgroup analysis of Latin American patients in the phase 3 randomized UNCOVER-3 study / Comparación de ixekizumab y etanercept o placebo en la psoriasis de moderada a grave: análisis del subgrupo de pacientes latinoamericanos de la fase 3 del estudio aleatorizado UNCOVER-3

Background and objectives: Ixekizumab demonstrated greater efficacy than placebo and etanercept in UNCOVER-3. Subgroup analysis of Latin American patients was performed. We report 12-week and 60-week data. Patients and methods: Analysis included 102 Latin American patients randomized to receive placebo (n = 14), etanercept 50 mg twice weekly (n=30), or ixekizumab 160-mg starting dose followed by 80 mg every 2 weeks (Q2W; n = 29) or every 4 weeks (Q4W; n = 29). At week 12, patients maintaining efficacy response and adequate overall safety were assigned, at the discretion of the investigator, to long-term extension with ixekizumab Q4W. Results: At week 12, Psoriasis Area and Severity Index (PASI) 100 scores were 0%, 20.0% (p = 0.075 vs placebo), 62.1% (p < 0.001 vs placebo; p = 0.001 vs etanercept), and 48.3% (p = 0.002 vs placebo; p = 0.023 vs etanercept) for placebo, etanercept, ixekizumab Q2W, and ixekizumab Q4W, respectively. Among patients who continued therapy up to week 60 (n = 97), PASI 100 scores were 71.4%, 60.0%, 77.8%, and 57.7% for patients who received induction placebo, etanercept, ixekizumab Q2W, and ixekizumab Q4W, respectively (non-responder imputation). By week 60, ≥1 serious adverse event was experienced by 7.1% (n = 1/14), 3.3% (n = 1/30), 14.8% (n = 4/27), and 0% (n = 0/26) of patients who received induction placebo, etanercept, ixekizumab Q2W, and ixekizumab Q4W, respectively. There were no cases of active tuberculosis with ixekizumab treatment through 60 weeks. Conclusions: In Latin American patients, both ixekizumab dosing regimens demonstrated greater efficacy than etanercept for treating psoriasis over 12 weeks. The safety profile of ixekizumab through 60 weeks was well tolerated and consistent with the overall profile (AU)

Antecedentes y objetivos: Ixekizumab demostró una mayor eficacia que el placebo y etanercept en el estudio UNCOVER-3. Tras realizar un análisis del subgrupo de pacientes latinoamericanos, se presentan los resultados transcurridas 12 y 60 semanas. Pacientes y métodos: El análisis incluyó a 102 pacientes latinoamericanos aleatorizados para la administración de placebo (n=14), etanercept 50 mg 2 veces por semana (n = 30), o ixekizumab 160mg como dosis inicial y 80mg cada 2 semanas (Q2W; n=29) o 4 semanas (Q4W; n = 29). A la semana 12 los pacientes con buena respuesta de eficacia y ausencia de efectos adversos fueron asignados al tratamiento de ampliación a largo plazo con ixekizumab Q4W, a discreción del investigador. Resultados: A las 12 semanas las puntuaciones del PASI fueron del 0%, 20% (p = 0,075 vs placebo), 62,1% (p < 0,001 vs placebo; p = 0,001 vs etanercept) y 48,3% (p = 0,002 vs placebo; p = 0,023 vs etanercept) para placebo, etanercept, ixekizumab Q2W, e ixekizumab Q4W, respectivamente. Entre los pacientes que prosiguieron la terapia hasta la semana 60 (n = 97) las puntuaciones PASI 100 fueron del 71,4%, 60%, 77,8%, y 57,7% para los pacientes a quienes se administró placebo de inducción, etanercept, ixekizumab Q2W e ixekizumab Q4W, respectivamente (imputación del no respondedor). En la semana 60 ≥1 presentaron reacción adversa grave el 7,1% (n = 1/14), 3,3% (n = 1/30), 14,8% (n = 4/27) y 0% (n = 0/26) de los pacientes a quienes se administró placebo, etanercept, ixekizumab Q2W e ixekizumab Q4W, respectivamente. No se produjeron casos de tuberculosis activa con el tratamiento de ixekizumab a lo largo de las 60 semanas. Conclusiones: En los pacientes latinoamericanos ambos regímenes de dosificación de ixekizumab demostraron mayor eficacia que etanercept para el tratamiento de la psoriasis durante 12 semanas. En cuanto al perfil de seguridad, ixekizumab a lo largo de 60 semanas fue bien tolerado y consistente con el perfil general (AU)

Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis: Subgroup analysis of Latin American patients in the phase 3 randomized UNCOVER-3 study.

BACKGROUND AND OBJECTIVES: Ixekizumab demonstrated greater efficacy than placebo and etanercept in UNCOVER-3. Subgroup analysis of Latin American patients was performed. We report 12-week and 60-week data. PATIENTS AND METHODS: Analysis included 102 Latin American patients randomized to receive placebo (n=14), etanercept 50mg twice weekly (n=30), or ixekizumab 160-mg starting dose followed by 80mg every 2 weeks (Q2W; n=29) or every 4 weeks (Q4W; n=29). At week 12, patients maintaining efficacy response and adequate overall safety were assigned, at the discretion of the investigator, to long-term extension with ixekizumab Q4W. RESULTS: At week 12, Psoriasis Area and Severity Index (PASI) 100 scores were 0%, 20.0% (p=0.075 vs placebo), 62.1% (p<0.001 vs placebo; p=0.001 vs etanercept), and 48.3% (p=0.002 vs placebo; p=0.023 vs etanercept) for placebo, etanercept, ixekizumab Q2W, and ixekizumab Q4W, respectively. Among patients who continued therapy up to week 60 (n=97), PASI 100 scores were 71.4%, 60.0%, 77.8%, and 57.7% for patients who received induction placebo, etanercept, ixekizumab Q2W, and ixekizumab Q4W, respectively (non-responder imputation). By week 60, ≥1 serious adverse event was experienced by 7.1% (n=1/14), 3.3% (n=1/30), 14.8% (n=4/27), and 0% (n=0/26) of patients who received induction placebo, etanercept, ixekizumab Q2W, and ixekizumab Q4W, respectively. There were no cases of active tuberculosis with ixekizumab treatment through 60 weeks. CONCLUSIONS: In Latin American patients, both ixekizumab dosing regimens demonstrated greater efficacy than etanercept for treating psoriasis over 12 weeks. The safety profile of ixekizumab through 60 weeks was well tolerated and consistent with the overall profile.