Research capacity training for surveillance and response in the Indo-Pacific: a case study of implementation.

SETTING: Surveillance and response workforce in the Indo-Pacific region, including Papua New Guinea (PNG), Solomon Islands, Fiji, Eastern Indonesia and Timor-Leste. OBJECTIVE: To evaluate the implementation of a modified WHO SORT IT research training programme which included a workplace-based research project. The training was designed for surveillance and response frontline workforce in the Indo-Pacific region. DESIGN: This was a programme evaluation using mixed methods. Fifty-three health and biosecurity workers from Fiji, Indonesia, PNG, Solomon Islands and Timor-Leste participated in the research training programme. RESULTS: Implementation of the programme was modified to reflect the context of participant countries. Work-place research projects focused on priority issues identified by local policy makers and in-country stakeholders. Self-reported research skills showed a significant increase (P < 0.01) after the completion of training. Participants reported high scores for satisfaction with training. CONCLUSIONS: This case study provides lessons learnt for future research training, and demonstrates that the SORT IT model can be modified to reflect the context of implementation without compromising purpose or outcomes.

CONTEXTE: Personnel de surveillance et d'intervention dans la région Indo-Pacifique incluant la Papouasie-Nouvelle-Guinée (PNG), les îles Salomon, les Fiji, l'Est de l'Indonesia et Timor-Leste. OBJECTIF: Évaluer la mise en œuvre d'un programme de formation modifiée WHO SORT-IT incluant un projet de recherche sur les lieux de travail. La formation était conçue pour le personnel de surveillance et d'intervention de première ligne dans la région Indo-Pacifique. SCHÉMA: Evaluation de programme utilisant des méthodes mixtes. Cinquante-trois travailleurs en matière de santé et de biosécurité venant des Fiji, d'Indonesie, de PNG, des îles Salomon et du Timor-Leste ont participé au programme de formation à la recherche. RÉSULTATS: La mise en œuvre du programme a été modifiée pour refléter le contexte des pays participants. Les projets de recherche sur les lieux de travail se sont focalisés sur les problèmes prioritaires identifiés par les responsables de la politique locale et les parties prenantes du pays. Les capacités de recherche rapportées par les participants ont montré une augmentation significative (P < 0,01) après la fin de la formation. Les participants ont exprimé de hauts scores de satisfaction à propos de la formation. CONCLUSION: Cette étude de cas fournit des leçons pour les formations en recherche à venir et démontré que le modèle SORT IT pouvait être modifié pour refléter le contexte de sa mise en œuvre sans compromettre le but ni les résultats.

Pleomorphic dermal sarcoma: a clinical and histological review of 49 cases.

Pleomorphic dermal sarcoma (PDS) is a rare mesenchymal neoplasm that shares histopathological features with atypical fibroxanthoma (AFX), but has additional features of deep invasion of the superficial subcutis, tumour necrosis, and vascular and perineural invasion, which confers a risk of local recurrence and metastases. To study the clinical and pathological spectrum more comprehensively, we retrieved 49 cases of pleomorphic dermal sarcoma from our departmental files. There was a strong male predominance (n=45). The mean (range) age at presentation was 80 (47-97) years. The tumours had a median (range) maximum dimension of 23.5 (5-75) mm. There was a strong predilection for the head and face (n=47), with the scalp (n=32) being the most common site. Ulceration was observed in 21 patients, tumour necrosis in seven, perineural infiltration in six, and lymphovascular invasion in two. CD10 was expressed in all cases. Smooth muscle actin was expressed in 15 and CD68 in 14. Follow up was available in 41 cases (mean (range) 22.4 (2-90) months). Six patients had local recurrences, despite all having originally undergone primary surgical resections and having reports of clear margins. Progressive metastatic disease was observed in one patient who died from their disease. Based on the Kaplan Meier method, median overall survival was 70.8 (8.4-133.1) months. Although AFX and PDS may be part of a spectrum, distinction is important to emphasise the potential for malignant behaviour in PDS.

Transgressive women don't deserve protection: young men's narratives of sexual violence against women in rural Papua New Guinea.

Sexual violence against women and girls is commonplace in Papua New Guinea (PNG). While the experiences of women are rightly given central place in institutional responses to sexual violence, the men who perpetrate violence are often overlooked, an oversight that undermines the effectiveness of prevention efforts. This paper draws on interviews conducted with young men as part of a qualitative longitudinal study of masculinity and male sexuality in a rural highland area of PNG. It explores one aspect of male sexuality: men's narratives of sexual violence. Most striking from the data is that the collective enactment of sexual violence against women and girls is reported as an everyday and accepted practice amongst young men. However, not all women and girls were described as equally at risk, with those who transgress gender roles and roles inscribed and reinforced by patriarchal structures, at greater risk. To address this situation, efforts to reduce sexual violence against women and girls require an increased focus on male-centred intervention to critically engage with the forms of patriarchal authority that give license to sexual violence. Understanding the perceptions and experiences of men as perpetrators of sexual violence is a critical first step in the process of changing normative perceptions of gender, a task crucial to reducing sexual violence in countries such as PNG.

Marking sutures to orientate specimens of basal cell carcinoma: do they really make a difference?

Traditionally, marking sutures have been used to orientate specimens of non-melanomatous skin cancers, and they provide an identifiable point as a reference for monitoring and further treatment. For histopathological purposes, the orientated specimen is marked with different inks, which enables measurement to the nearest lateral and deep margins, and if invaded, guides further excision. We retrospectively analysed 688 specimens of basal cell carcinoma (BCC) from the head and neck from two separate years: 2010 and 2012. Marking sutures were used in 663 (96%) cases. There were 21 invaded margins (3%), 17 (81%) at the lateral margin and 4 (19%) at the deep margin. Of the 17 with invaded lateral margins, 10 were from the nose, and the remaining 7 from other sites including the ear (n=2), and neck, forehead, temple, eyelid, and cheek (n=1 each). Of the 663 marked specimens, the marking stitch was useful in only one patient who needed another operation (0.2%). We suggest that routine orientation of BCC, even from high risk areas, is not necessary. If the operating surgeon questions the size of the margin when a lesion is ill-defined or of a high-risk histological subtype, then excision with monitored en-face margins should be considered with traditional Mohs surgery or a reliable modified version.

Environmental factors that affect the Fukuda stepping test in normal participants.

BACKGROUND: The Fukuda stepping test is commonly used to assess peripheral vestibular function. It has, however, been suggested that its maximal sensitivity and specificity are 70 per cent and 50 per cent, respectively. This study was undertaken to evaluate environmental factors that may influence the reliability of this assessment and hence to 'sharpen' its use in a clinical setting. METHODS: Forty-four participants aged between 20 and 43 years were asked to perform the Fukuda stepping test in both a standard clinic room and a soundproofed room under the following conditions in a randomised order: on the floor versus on foam; with and without a sound-localising source; and with and without ear defenders. RESULTS: Significant differences in the extent of rotation were found when comparing the results obtained in several settings, including standing on the floor in a standard room versus a soundproofed room (p = 0.036), and standing on foam in a standard room versus a soundproofed room (p = 0.015). CONCLUSION: Our results suggest that certain alterations to the test environment may improve the sensitivity of this clinical examination.

Assessing the Unterberger test: introduction of a novel smartphone application.

BACKGROUND: Peripheral vestibular function is commonly assessed using the Unterberger test. Patients are asked to march on the spot and their extent of rotation is recorded. The sensitivity of this test depends on an assessor accurately estimating the degree of rotation. This study therefore aimed to compare observer estimates with a smartphone application (DplusR Balance) that accurately records rotation. METHOD: Twenty-five participants were asked to estimate the degree of rotation in 10 successive Unterberger tests performed by a volunteer. RESULTS: The average difference between estimated and application recorded extent of rotation was 30°. CONCLUSION: Assessors poorly estimate the degree of rotation in this clinical test, to an extent sufficient to affect clinical interpretation and diagnosis. We recommend the use of this application or alternative methods to record the degree of rotation in patients.

Hearing outcomes following primary malleostapedial rotation ossiculoplasty in patients undergoing modified radical mastoidectomy.

INTRODUCTION: Treatment of cholesteatoma consists of either excision or exteriorisation of disease. Approaches have traditionally included a radical or modified radical mastoidectomy and combined approach tympanoplasty. Hearing thresholds following a modified radical mastoidectomy alone have been reported as poor. We assessed hearing outcomes in patients undergoing a primary malleostapedial reconstruction combined with their open cavity surgery. METHODS: All patients undergoing open cavity mastoidectomy with primary malleostapedial rotation ossiculoplasty between 2009 and 2013 were identified. Case notes were reviewed, and demographic data, recurrence rate and audiometry were recorded. RESULTS: Twenty-one patients were identified. The age range was 10-65 years. There was no evidence of recurrence of cholesteatoma. The mean postoperative air-bone gap was 20dBHL, 23dBHL, 10dBHL and 27dBHL at 0.5kHz, 1kHz, 2kHz and 4kHz respectively. Excluding cases consistent with a postoperative ossicular discontinuity (n=3), the mean postoperative air-bone gap was 15dBHL, 19dBHL, 8dBHL and 26dBHL at 0.5kHz, 1kHz, 2kHz and 4kHz respectively. CONCLUSIONS: The improvement in hearing thresholds demonstrated in this cohort of patients supports the use of this form of ossiculoplasty in those undergoing open cavity procedures. This would also suggest that the subsequent use of hearing aids in these patients would require less amplification and therefore provide superior hearing outcomes. As hearing loss remains a significant concern following modified radical mastoidectomy, we suggest an open cavity with primary malleostapedial rotation ossiculoplasty as a viable alternative to modified radical mastoidectomy alone, in selected cases.

Hydrophobically-associating cationic polymers as micro-bubble surface modifiers in dissolved air flotation for cyanobacteria cell separation.

Dissolved air flotation (DAF), an effective treatment method for clarifying algae/cyanobacteria-laden water, is highly dependent on coagulation-flocculation. Treatment of algae can be problematic due to unpredictable coagulant demand during blooms. To eliminate the need for coagulation-flocculation, the use of commercial polymers or surfactants to alter bubble charge in DAF has shown potential, termed the PosiDAF process. When using surfactants, poor removal was obtained but good bubble adherence was observed. Conversely, when using polymers, effective cell removal was obtained, attributed to polymer bridging, but polymers did not adhere well to the bubble surface, resulting in a cationic clarified effluent that was indicative of high polymer concentrations. In order to combine the attributes of both polymers (bridging ability) and surfactants (hydrophobicity), in this study, a commercially-available cationic polymer, poly(dimethylaminoethyl methacrylate) (polyDMAEMA), was functionalised with hydrophobic pendant groups of various carbon chain lengths to improve adherence of polymer to a bubble surface. Its performance in PosiDAF was contrasted against commercially-available poly(diallyl dimethyl ammonium chloride) (polyDADMAC). All synthesised polymers used for bubble surface modification were found to produce positively charged bubbles. When applying these cationic micro-bubbles in PosiDAF, in the absence of coagulation-flocculation, cell removals in excess of 90% were obtained, reaching a maximum of 99% cell removal and thus demonstrating process viability. Of the synthesised polymers, the polymer containing the largest hydrophobic functionality resulted in highly anionic treated effluent, suggesting stronger adherence of polymers to bubble surfaces and reduced residual polymer concentrations.

Metal-binding hydrogel particles alleviate soil toxicity and facilitate healthy plant establishment of the native metallophyte grass Astrebla lappacea in mine waste rock and tailings.

Soil contaminants are potentially a major threat to human and ecosystem health and sustainable production of food and energy where mineral processing wastes are discharged into the environment. In extreme conditions, metal concentrations in wastes often exceed even the metal tolerance thresholds of metallophytes (metal-tolerant plants) and sites remain barren with high risks of contaminant leaching and dispersion into the environment via erosion. A novel soil amendment based on micron-size thiol functional cross-linked acrylamide polymer hydrogel particles (X3) binds toxic soluble metals irreversibly and significantly reduces their concentrations in the soil solution to below the phytotoxicity thresholds. X3 mixed into the top 50mm of phytotoxic mine waste materials in pots in glasshouse conditions reduced total soluble concentrations of toxic contaminants by 90.3-98.7% in waste rock, and 88.6-96.4% in tailings immediately after application. After 61 days, quality of unamended bottom layer of X3-treated pots was also significantly improved in both wastes. Combination of X3 and metallophytes was more efficient at improving soil solution quality than X3 alone. Addition of X3 to substrates increased substrate water retention and water availability to plants by up to 108% and 98% for waste rock and tailings respectively. Soil quality improvement by X3 allowed successful early establishment of the native metallophyte grass Astrebla lappacea on both wastes where plants failed to establish otherwise.

Micron-size metal-binding hydrogel particles improve germination and radicle elongation of Australian metallophyte grasses in mine waste rock and tailings.

Metal contamination of landscapes as a result of mining and other industrial activities is a pervasive problem worldwide. Metal contaminated soils often lack effective vegetation cover and are prone to contaminant leaching and dispersion through erosion, leading to contamination of the environment. Metal-binding hydrogel particle amendments could ameliorate mine wastes prior to planting and enhance seedling emergence. In this study, micron-size thiol functional cross-linked acrylamide polymer hydrogel particles (X3) were synthesised and tested in laboratory-scale experiments on phytotoxic mine wastes to determine their capacity to: (i) increase substrate water holding capacity (WHC); (ii) reduce metal availability to plants to below the phytotoxicity threshold; and (iii) enhance germination characteristics and early radicle development of two Australian metallophyte grasses under limiting and non-limiting water conditions. Addition of X3 to mine wastes significantly increased their WHC and lowered toxic soluble metal concentrations in mine waste leachates. Germination percentages and radicle elongation of both grasses in wastes were significantly increased. Highest germination percentages and greater radicle development recorded in X3 amended wastes under water limited conditions suggests that X3 was able to ameliorate metal toxicity to radicles, and provide moisture, which improved the imbibition and consequent germination of the seeds.

Aged monkeys as a partial model for Parkinson's disease.

Parkinson's Disease (PD) and the natural aging process share a number of biochemical mechanisms, including reduced function of dopaminergic systems. The present study aims to determine the extent that motor and behavioral changes in aged monkeys resemble parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The behavioral and physiological changes in PD are believed to result largely from selective depletion of dopamine in the nigrostriatal system. In the present study, ten aged female monkeys were compared with three groups: 9 untreated young adult female monkeys, 10 young adult male monkeys and 13 older male monkeys that had been exposed to MPTP. Trained observers, blind as to age and drug condition and without knowledge of the hypotheses, scored the monkeys using the Parkinson's factor score (Parkscore), which has been validated by a high correlation with post mortem striatal dopamine (DA) concentrations. The aged animals had higher scores on the Parkscore compared with the young adults, with most of its component behavioral items showing significance (tremor, Eating Problems, Delayed initiation of movement, and Poverty of Movement). L-Dopa and DA-agonists did not clearly reverse the principal measure of parkinsonism. DA concentrations post mortem were 63% lower in 3 aged monkeys in the ventral putamen compared with 4 young adults, with greater reductions in putamen than in caudate (45%). We conclude that aged monkeys, unexposed to MPTP, show a similar profile of parkinsonism to that seen after the neurotoxin exposure to MPTP in young adult monkeys. The pattern of greater DA depletion in putamen than in caudate in aged monkeys is the same as in human Parkinson's disease and contrasts with the greater depletion in caudate seen after MPTP. Aged monkeys of this species reflect many facets of Parkinson's disease, but like older humans do not improve with standard dopamine replacement pharmacotherapies.

Metal-binding particles alleviate lead and zinc toxicity during seed germination of metallophyte grass Astrebla lappacea.

Combining metal-binding particles and metal-tolerant plants (metallophytes) offers a promising new approach for rehabilitation of heavy metal contaminated sites. Three types of hydrogel metal-binding polymer particles were synthesized and their effects on metal concentrations tested in vitro using metal ion solutions. The most effective of the tested polymers was a micron-sized thiol functional cross-linked acrylamide polymer which reduced the available solution concentrations of Pb(2+) (9.65 mM), Cu(2+) (4mM) and Zn(2+) (10mM) by 86.5%, 75.5% and 63.8%, respectively, and was able to store water up to 608% of its dry mass. This polymer was not toxic to seed germination. In deionised water, it enhanced seed germination, and at otherwise phytotoxic Pb(2+) (9.65 mM) and Zn(2+) (10mM) concentrations, it allowed normal germination and root elongation of the metallophyte grass Astrebla lappacea. We conclude that the polymer has the potential to facilitate restoration of heavy metal contaminated lands by reducing the concentration of metal cations in the soil solution and improving germination rates through reduced toxicity and enhanced plant water relations.

Fragment based drug discovery using fluorescence correlation: spectroscopy techniques: challenges and solutions.

Novel starting points for medicinal chemistry programmes can be effectively identified by screening libraries of fragment molecules in biochemical assays at high concentration. The key to success with this approach is the combination of a high quality fragment library with sensitive biochemical screening methods. There are an increasing number of literature reports where weakly active fragment molecules have been identified by high concentration biochemical assays. We have successfully demonstrated the use of high concentration screening of fragments, using a portfolio of single-molecule Fluorescence Correlation Spectroscopy (FCS+plus) detection techniques to ensure the highest reproducibility and sensitivity, and have determined the binding mode of active fragments to target proteins by X-ray crystallography. Further biophysical detection methods are reviewed for their applicability to studies of fragment binding.

Nupafant, a PAF-antagonist prototype for suppression of ventricular fibrillation without liability for QT prolongation?

BACKGROUND AND PURPOSE: PAF antagonists inhibit ischaemia-induced ventricular fibrillation (VF) in animals. However, unfavourable ancillary actions (on QT interval and coronary flow) have been reported with the PAF antagonist, BN-50739. If these are class actions, they would preclude development of PAF antagonists as novel anti-VF drugs. Our purpose was to examine this proposition using the hitherto untested PAF antagonist, nupafant. EXPERIMENTAL APPROACH: Two rat heart preparations (Langendorff and 'dual coronary' perfusion) were used to assay nupafant's effects on ischaemia-induced VF, coronary flow and QT interval, and to test for the site-selectivity necessary if any effects on VF are caused by PAF antagonism. KEY RESULTS: Global (whole-heart) delivery of 10 microM nupafant, reduced the incidence of ischaemia-induced VF and widened QT interval without affecting coronary flow. Importantly, lower concentrations (0.1 and 1 microM) had no effect on VF, yet widened QT almost identically to 10 microM nupafant. When nupafant was delivered selectively to (and entrapped within) the involved region it partially protected against VF (P<0.05). This occurred without change in QT interval. Selective nupafant delivery to the uninvolved region was without effect. CONCLUSIONS AND IMPLICATIONS: Nupafant protects against ischaemia-induced VF primarily by site-selective actions in the ischaemic region but, unlike BN-50739, the effect is unrelated to its QT widening action, and is not compromised by any effect on coronary flow. This establishes proof of concept that VF suppression by PAF antagonism need not invariably be associated with QT prolongation or vasodilatation, justifying further development of this drug class.

Level walking and ambulatory capacity in persons with incomplete spinal cord injury: relationship with muscle strength.

STUDY DESIGN: Prospective analysis of relationships. OBJECTIVES: (1) To quantify the relationship between individual lower extremity muscle strength and functional walking measures and (2) to determine whether a multiple regression model incorporating lower extremity muscle strength could predict the performance of functional walking measures in persons with incomplete spinal cord injury (ISCI) living in the community. SETTING: Tertiary rehabilitation center, Vancouver, Canada. METHODS: In all, 22 subjects with ISCI participated. The relationship between functional walking measures (gait speed, 6-min-walk distance, and ambulatory capacity) and muscle strength (manual tests of hip flexors/extensors/abductors, knee flexors/extensors, ankle dorsiflexors/plantarflexors, and great toe extensors) were measured by Pearson's correlation and regression procedures. RESULTS: For both the more and less affected sides, hip flexors, hip extensors, and hip abductors produced the highest correlations with the three functional measures. The less affected hip flexor strength explained more than 50% of the variance in gait speed and 6-min-walk distance while the less affected hip extensor strength explained up to 64% of the variance in ambulatory capacity. For all three functional measures, the strength of the less affected limb was more important than that of the more affected limb. CONCLUSIONS: Lower extremity muscle strength, in particular that of hip flexors, hip extensors, and hip abductors, is an important determinant of functional walking performance.

Saving clinicians' time by delegating routine aspects of therapy to a computer: a randomized controlled trial in phobia/panic disorder.

BACKGROUND: The demand for time-consuming psychotherapy of phobia/panic exceeds the supply of trained therapists. Delegating routine therapy aspects to a computer might ease this problem. METHOD: Ninety-three out-patients with phobia or panic disorder were randomized in a 2: 2 : 1 ratio to have self-exposure therapy guided either mainly by a stand-alone computer system (FearFighter) or entirely face-to-face by a clinician, or to have mainly computer-guided self-relaxation as a placebo. Both computer groups (FearFighter and relaxation) had brief back-up advice from a clinician. Primary outcome measures were self- and blind-assessor ratings of Main Problem and Goals, and Global Phobia. RESULTS: Drop-outs occurred significantly more often in the two self-exposure groups (43% if mainly computer-guided, 24% if entirely clinician-guided) than with self-relaxation (6%); the difference between the two self-exposure groups was not significant. Even with all drop-outs included, the mainly computer-guided exposure group and the relaxation group had 73% less clinician time per patient than did the entirely clinician-guided exposure group. The two self-exposure groups had comparable improvement and satisfaction at post-treatment and at 1-month follow-up, while relaxation was ineffective. Mean improvement on the primary outcome measures (self- and assessor-rated) was 46% computer, 49% clinician, 9% relaxation at post-treatment (week 10) and 58% computer, 53% clinician and -4% relaxation at 1-month follow-up (week 14). Mean effect sizes on the primary outcome measures were 2.9 computer, 3.5 clinician and 0.5 relaxation at post-treatment; and 3.7 computer, 3.5 clinician and 0.5 relaxation at 1-month follow-up. The assessor did not rate patients at follow-up. CONCLUSIONS: Despite its (non-significantly) higher dropout rate, self-exposure therapy for panic/ phobia cut clinician time per patient by 73% without losing efficacy when guided mainly by a computer rather than entirely by a clinician. The finding needs confirmation at a follow-up that is longer and includes a blind assessor. Self-relaxation had the highest rate of completers but was ineffective.

Mucinous metaplasia of the penis.

AIMS: To determine the incidence of mucinous metaplasia occurring in the foreskin or glans penis and any associated clinical or histopathological features. METHODS AND RESULTS: Following the recognition of two index cases, 100 other foreskin specimens were retrieved from the histopathology archives at Southampton General Hospital. The haematoxylin and eosin-stained slides were examined by a single observer to detect the presence of mucin-producing cells in the surface epithelium. The absence of mucinous metaplasia in negative cases was confirmed with mucin histochemistry. In total, four cases of mucinous metaplasia were identified, three involving the foreskin and one involving the glans penis. The age range was 51-80 years. Three cases were associated with Zoon's balanitis and the fourth showed mild non-specific balanitis. All four cases showed positive staining with both diastase periodic acid-Schiff and alcian blue. No mucin-producing cells were identified in non-inflamed or minimally inflamed specimens. CONCLUSIONS: Mucinous metaplasia of the penis is an uncommon but under-recognized condition. It is seen in the elderly and appears to be a metaplastic change associated with severe chronic inflammation, and possibly more specifically with Zoon's balanitis. Our study identified a case affecting the glans penis, a site not previously recorded.