Disability workforce and the NDIS planning process in regional, rural and remote regions of Australia: Scoping review.

BACKGROUND: The Australian geographically rural and remote disability workforce has historically demonstrated difficulties to keep up with the demand for quality services and supports for people with disability. In 2013, the National Disability Insurance Scheme (NDIS) was launched to provide individualised disability support packages to meet people's needs. To receive funding, people with disability are required to develop a NDIS plan. That plan is then funded by the National Disability Insurance Agency (NDIA), the government agency responsible for managing the NDIS. Although the NDIS has been operating for almost 10 years, there is limited research into the planning experiences of the workforce in regional, rural and remote regions of Australia. This review aims to ascertain the level of scholarly investigation into workers' experiences of NDIS planning. METHODOLOGY: Research publication databases were searched using a specific search string to identify publications that included reference to the workforce's experiences of the NDIS planning process in regional, rural and remote regions of Australia. The Mixed Methods Appraisal Tool (MMAT) was adopted to appraise the quality of the research publications. Research publications that focused on those working with Aboriginal and Torres Strait Islander people were also appraised using the Aboriginal and Torres Strait Islander Quality Appraisal Tool developed by the Centre for Excellence in Aboriginal Chronic Disease Knowledge Translation and Exchange. A thematic synthesis of the publications was undertaken to ascertain disability and health workforce experiences of the NDIS planning process. RESULTS: Seven papers met the selection criteria. Two papers were policy reviews and reported the improvements of the NDIS planning process since its inception. These studies reported four reoccurring themes: (1) cultural/socioeconomic and geographical factors; (2) administrative burden and bureaucracy; (3) values, culture and geography; and (4) burden on allied health workers. CONCLUSION: The NDIS planning process has developed and progressed since its rollout in 2013. There are limited research papers available that describe the workforce's experience of the planning process in regional, rural and remote regions. More research in this area is needed to identify the experiences of the disability workforce in relation to the NDIS planning process.

The experiences of people with disability and their families/carers navigating the NDIS planning process in regional, rural and remote regions of Australia: Scoping review.

BACKGROUND: Australia's National Disability Insurance Scheme (NDIS) was launched in 2013 to provide financial support packages for people with disability to purchase supports and services to enhance independence. People with disability are required to develop a plan with the National Disability Insurance Agency (NDIA), the government department responsible for managing the NDIS. This scoping review aims to ascertain the level of research into people's experience of the NDIS planning process in these geographic areas. METHODOLOGY: Research publication databases were searched using a specific search string to identify research about people with disability and their families/carer's experiences of the NDIS planning process in regional, rural and remote regions of Australia. The Mixed Methods Appraisal Tool (MMAT) was adopted to appraise the quality of the research publications. Research publications focused on Aboriginal and Torres Strait Islander people were additionally appraised using the Aboriginal and Torres Strait Islander Quality Appraisal Tool developed by the Centre for Excellence in Aboriginal Chronic Disease Knowledge Translation and Exchange. A thematic synthesis of the publications' contents was undertaken to ascertain people with disabilities and carers experience of the NDIS planning process. RESULTS: Ten (N = 10) research papers were found that met the inclusion criteria. Two papers were policy reviews and reported on the improvements of the NDIS planning process since its conception. The analysis found the research archive focused on five themes: (1) healthcare workforce and NDIA staff; (2) NDIS package holders and carers lack of awareness of the NDIS; (3) cultural/socio-economic barriers; (4) travel funding; and (5) emotional burden of the NDIS planning process. CONCLUSION: There are limited papers available that explore people's experiences of the NDIS planning process in regional, rural and remote regions of Australia. This systematic review illuminates the difficulties, barriers and concerns of people with disability and their carers about the planning process.

Assessment of the safety, pharmacokinetics and pharmacodynamics of GSK3335065, an inhibitor of kynurenine monooxygenase, in a randomised placebo-controlled first-in-human study in healthy volunteers.

GSK3335065 is an inhibitor of kynurenine monooxygenase (KMO) being developed for the treatment of acute pancreatitis. Healthy male volunteers were administered ascending doses of GSK3335065 or matched placebo as a single intravenous bolus injection to assess safety, tolerability, pharmacokinetics and pharmacodynamics. GSK3335065 displayed an apparent volume of distribution between 20.6 L and 44.6 L, a clearance between 0.462 L/h and 0.805 L/hr and a terminal half-life between 31.3 and 34.5 hr. In the single subject who received 1.3 mg GSK3335065, changes in tryptophan pathway metabolites were observed consistent with the changes seen in preclinical species suggesting that KMO enzyme activity was partially inhibited. However, a broad complex ventricular tachycardia was observed in this subject, which was judged to be a Serious Adverse Event (SAE) and resulted in early termination of the study. While development of GSK3335065 was subsequently discontinued, significant confounding factors hinder a clear interpretation that the tachycardia was directly related to administration of the compound.

ASSOCIATION BETWEEN SINGLE-PARENT FAMILY STRUCTURE AND AGE OF SEXUAL DEBUT AMONG YOUNG PERSONS IN JAMAICA.

There is a high and increasing proportion of single-parent families in Jamaica. This has raised concerns about the potential impact of single-parent families on the social, cognitive and behavioural development of children, including their sexual relationships. The aim of this study was to investigate the association between being raised in a single-parent family and age of sexual debut among young people in Jamaica. The study was cross-sectional in design, and based on a multi-stage sampling procedure. The study was conducted in July/September 2016. The study sample comprised 233 respondents (110 males and 123 females) aged from 18 to 35 years (mean 26.37 years; SD 5.46). Respondents completed a self-administered questionnaire with questions on socio-demographic characteristics, family structure, sexual debut and current sexual behaviour. Ninety-seven (41.7%) respondents grew up in single-parent families. A total of 201 (86.3%) had had sex (102 males and 99 females). Their mean age of sexual debut was 15.51 years (SD 3.41). Sixty-five (32.3%) had early sexual debut (<16 years). Respondents from single-parent families were more likely to have had early sexual debut (56.9%; n=37) compared with those from two-parent families (43.1%, n=28; p=0.004). Only 44.6% (n=29) of those who experienced early sexual debut used a condom during their first sexual encounter compared with 73% (n=100) of those who had a later sexual debut (≥16 years; p=<0.001). A single-father family structure was a significant predictor of early sexual debut (AOR 5.5; 95%CI: 1.1-25.8). The study found a significant association between single-parent family structure and age of sexual debut.

Hair analysis to monitor adherence to prescribed chronic inhaler drug therapy in patients with asthma or COPD.

BACKGROUND: Poor adherence to inhaled drug therapy in individuals with asthma and/or chronic obstructive pulmonary disease (COPD) may be associated with suboptimal therapeutic outcomes. Measurement of drug residues in hair samples has been employed to assess oral medication use over time. Here, we test the feasibility of analyzing hair samples from patients with asthma and/or COPD for assessing adherence to prescribed inhaled medication. METHODS: In total, 200 male and female subjects, ≥ 18 years of age, with stable asthma and/or COPD who were receiving an acceptable standard of care daily inhaled product consistently, were recruited. Head hair samples were taken during a single visit to the clinical site and grouped by hair color according to the Fischer-Saller scale. Drug residues were extracted from milled hair samples using solid-phase extraction and analyzed using liquid chromatography-tandem mass spectrometry. RESULTS: Inhaled drugs were detected in hair for 72% of subjects from whom it was possible to analyze hair samples (n = 157/200). Most hair samples obtained from subjects receiving formoterol or vilanterol had amounts of drug present that allowed determination of a quantifiable concentration, and demonstrated a dose response. Drugs were detected in all hair colors, with higher concentrations of formoterol observed in dark-haired versus light-haired individuals. CONCLUSIONS: This is the first study to demonstrate that inhaled medication can be measured in hair samples from subjects with asthma and/or COPD. The results show that hair drug concentration data could potentially provide a record of historical adherence to inhaled therapeutics.

Increased levels of 3-hydroxykynurenine parallel disease severity in human acute pancreatitis.

Inhibition of kynurenine 3-monooxygenase (KMO) protects against multiple organ dysfunction (MODS) in experimental acute pancreatitis (AP). We aimed to precisely define the kynurenine pathway activation in relation to AP and AP-MODS in humans, by carrying out a prospective observational study of all persons presenting with a potential diagnosis of AP for 90 days. We sampled peripheral venous blood at 0, 3, 6, 12, 24, 48, 72 and 168 hours post-recruitment. We measured tryptophan metabolite concentrations and analysed these in the context of clinical data and disease severity indices, cytokine profiles and C-reactive protein (CRP) concentrations. 79 individuals were recruited (median age: 59.6 years; 47 males, 59.5%). 57 met the revised Atlanta definition of AP: 25 had mild, 23 moderate, and 9 severe AP. Plasma 3-hydroxykynurenine concentrations correlated with contemporaneous APACHE II scores (R2 = 0.273; Spearman rho = 0.581; P < 0.001) and CRP (R2 = 0.132; Spearman rho = 0.455, P < 0.001). Temporal profiling showed early tryptophan depletion and contemporaneous 3-hydroxykynurenine elevation. Furthermore, plasma concentrations of 3-hydroxykynurenine paralleled systemic inflammation and AP severity. These findings support the rationale for investigating early intervention with a KMO inhibitor, with the aim of reducing the incidence and severity of AP-associated organ dysfunction.

50 kHz capacitive micromachined ultrasonic transducers for generation of highly directional sound with parametric arrays.

In this study, we examine the use of capacitive micromachined ultrasonic transducers (CMUTs) with vacuum- sealed cavities for transmitting directional sound with parametric arrays. We used finite element modeling to design CMUTs with 40-microm- and 60-microm-thick membranes to have resonance frequencies of 46 kHz and 54 kHz, respectively. The wafer bonding approach used to fabricate the CMUTs provides good control over device properties and the capability to fabricate CMUTs with large diameter membranes and deep cavities. Each CMUT is 8 cm in diameter and consists of 284 circular membranes. Each membrane is 4 mm in diameter. Characterization of the fabricated CMUTs shows they have center frequencies of 46 kHz and 55 kHz and 3 dB bandwidths of 1.9 kHz and 5.3 kHz for the 40-microm- and 60-microm-thick membrane devices, respectively. With dc bias voltages of 380 V and 350 V and an ac excitation of 200 V peak-to-peak, the CMUTs generate average sound pressure levels, normalized to the device's surface, of 135 dB and 129 dB (re 20 microPa), respectively. When used to generate 5 kHz sound with a parametric array, we measured sound at 3 m with a 6 dB beamwidth of 8.7 degrees and a sound pressure level of 58 dB. To understand how detector nonlinearity (e.g., the nonlinearity of the microphone used to make the sound level measurements) affects the measured sound pressure level, we made measurements with and without an acoustic low-pass filter placed in front of the microphone; the measured sound levels agree with numerical simulations of the pressure field. The results presented in this paper demonstrate that large-area CMUTs, which produce high-intensity ultrasound, can be fabricated for transmitting directional sound with parametric arrays.

Reply to Philipona and O'Regan.

This paper responds to Philipona and O'Regan (2006), which attempts to account for certain color phenomena by appeal to singularities in the space of "accessible information" in the light striking the retina. Three points are discussed. First, it is unclear what the empirical significance/import is of the mathematical analysis of the data regarding the accessible information in the light. Second, the singularity index employed in the study is both mathematically and empirically faulty. Third, the connection drawn between their findings and some data from the World Color Survey is lacking in quantitative analysis in places where it is needed. The difficulties raised prevent Philipona & O'Regan's conclusions from being accepted.

Determination of zanamivir in rat and monkey plasma by positive ion hydrophilic interaction chromatography (HILIC)/tandem mass spectrometry.

A hydrophilic interaction chromatography (HILIC)/mass spectrometric assay was developed for the determination of zanamivir, a neuraminidase inhibitor used to treat influenza, in rat and monkey plasma. An organic solvent with hydrophilic properties, methanol, was used to precipitate proteins in plasma to assure the highly polar zanamivir of staying in solution. Chromatographic separation was obtained using a HILIC silica column with multiple reaction monitoring turboionspray positive ion detection. The stable label of zanamivir, [(13)C(1)(15)N(2)] GR121167C, was used as the internal standard. The assay was validated for the determination of zanamivir in rat and monkey plasma. The lower and upper limits of quantitation were 2 and 10000 ng/mL, using 0.05 mL plasma aliquot, respectively. The signal to noise ratio of a typical 2 ng/mL was approximately 5:1. The inter-day precision (relative standard deviation) and accuracy (relative error) in rat plasma, derived from the analysis of validation samples at 5 concentrations, ranged from 6 to 10% and -6.5 to 0.2%, respectively. The inter-day precision (relative standard deviation) and accuracy (relative error) in monkey plasma, derived from the analysis of validation samples at five concentrations, ranged from 2 to 8% and -2.3 to 2.1%, respectively. Zanamivir was found to be stable for at least 5 days at approximately -80 degrees C and at room temperature in plasma. This assay incorporates a simple protein precipitation with methanol and hydrophilic interaction chromatography which is sensitive, accurate, precise, and is being used to support oral formulation and toxicokinetic studies in rat and monkey, respectively.

High-frequency measurements of blast wave propagation.

Blast wave propagation measurements were conducted to investigate nonlinear propagation effects on blast waveform evolution with distance. Measurements were made with a wide-bandwidth capacitor microphone for comparison with conventional 3.175-mm (1/8-in.) microphones with and without baffles. It was found that the 3.175-mm microphone did not have sufficient high-frequency response to capture the actual rise times in some regions. For a source of 0.57 kg (1.25 lb) of C-4 plastic explosive, the trend observed is that nonlinear effects steepened the waveform, thereby decreasing the shock rise time, up to a range of 50 m. At 100 m, the rise times had increased slightly.

Protein in sugar films and in glycerol/water as examined by infrared spectroscopy and by the fluorescence and phosphorescence of tryptophan.

Sugars are known to stabilize proteins. This study addresses questions of the nature of sugar and proteins incorporated in solid sugar films. Infrared (IR) and Raman spectroscopy was used to examine trehalose and sucrose films and glycerol/water solvent. Proteins and indole-containing compounds that are imbedded in the sugar films were studied by IR and optical (absorption, fluorescence, and phosphorescence) spectroscopy. Water is able to move in the sugar films in the temperature range of 20-300 K as suggested by IR absorption bands of HOH bending and OH stretching modes that shift continuously with temperature. In glycerol/water these bands reflect the glass transition at approximately 160 K. The fluorescence of N-acetyl-L-tryptophanamide and tryptophan of melittin, Ca-free parvalbumin, and staphylococcal nuclease in dry trehalose/sucrose films remains broad and red-shifted over a temperature excursion of 20-300 K. In contrast, the fluorescence of these compounds in glycerol/water solvent shift to the blue as temperature decreases. The fluorescence of the buried tryptophan in Ca-bound parvalbumin in either sugar film or glycerol/water remains blue-shifted and has vibronic resolution over the entire temperature range. The red shift for fluorescence of indole groups exposed to solvent in the sugars is consistent with the motion of water molecules around the excited-state molecule that occurs even at low temperature, although the possibility of static complex formation between the excited-state molecule and water or other factors is discussed. The phosphorescence yield for protein and model indole compounds is sensitive to the matrix glass transition. Phosphorescence emission spectra are resolved and shift little in different solvents or temperature, as predicted by the small dipole moment of the excited triplet state molecule. The conclusion is that the sugar film maintains the environment present at the glass formation temperature for surface Trp and amide groups over a wide temperature excursion. In glycerol/water these groups reflect local changes in the environment as temperature changes.

The hydration of amides in helices; a comprehensive picture from molecular dynamics, IR, and NMR.

We examined the hydration of amides of alpha(3)D, a simple, designed three-helix bundle protein. Molecular dynamics calculations show that the amide carbonyls on the surface of the protein tilt away from the helical axis to interact with solvent water, resulting in a lengthening of the hydrogen bonds on this face of the helix. Water molecules are bonded to these carbonyl groups with partial occupancy ( approximately 50%-70%), and their interaction geometries show a large variation in their hydrogen bond lengths and angles on the nsec time scale. This heterogeneity is reflected in the carbonyl stretching vibration (amide I' band) of a group of surface Ala residues. The surface-exposed amides are broad, and shift to lower frequency (reflecting strengthening of the hydrogen bonds) as the temperature is decreased. By contrast, the amide I' bands of the buried (13)C-labeled Leu residues are significantly sharper and their frequencies are consistent with the formation of strong hydrogen bonds, independent of temperature. The rates of hydrogen-deuterium exchange and the proton NMR chemical shifts of the helical amide groups also depend on environment. The partial occupancy of the hydration sites on the surface of helices suggests that the interaction is relatively weak, on the order of thermal energy at room temperature. One unexpected feature that emerged from the dynamics calculations was that a Thr side chain subtly disrupted the helical geometry 4-7 residues N-terminal in sequence, which was reflected in the proton chemical shifts and the rates of amide proton exchange for several amides that engage in a mixed 3(10)/alpha/pi-helical conformation.

Mixed trehalose/sucrose glasses used for protein incorporation as studied by infrared and optical spectroscopy.

Evaporation of water from a 1/1 mixture of trehalose and sucrose gives rise to optically clear glasses that are transparent in the UV and visible ranges and do not crystallize when they are prepared at ambient temperatures. Two proteins, liver alcohol dehydrogenase and parvalbumin, and the tryptophan derivative N-acetyl-tryptophanamide were incorporated into the glasses. Infrared spectroscopy of the amide I band reveals that the proteins retain secondary structure in the glass over a temperature range of 20-300K. The amide II band of the protein and the HOH bending band of residual water in the glass shift with temperature changes, consistent with increased H-bonding strength as temperature is lowered. Phosphorescence of tryptophan can be seen from the proteins at room temperature, which shows the immobilization of the protein by the glass and the curbing of oxygen diffusion. It is suggested that using mixed sugars to form glasses is a way to immobilize proteins over a wide temperature range without distortions from solvent crystals.

Optical and IR absorption as probe of dynamics of heme proteins.

The spectroscopy of horseradish peroxidase with and without the substrate analogue benzohydroxamic acid (BHA) was monitored in different solvents as a function of the temperature in the interval from 10 to 300 K. Thermal broadening of the Q(0,0) optical absorption band arises mainly from interaction of the electronic pi --> pi transition with the heme vibrations. In contrast, the width of the IR absorption band of CO bound to heme is controlled by the coupling of the CO transition moment to the electric field of the protein matrix. The IR bandwidth of the substrate free enzyme in the glycerol/H2O solvent hardly changes in the glassy matrix and strongly increases upon heating above the glass transition. Heating of the same enzyme in the trehalose/H2O glass considerably broadens the band. The binding of the substrate strongly diminishes the temperature broadening of the CO band. This result is consistent with the view that the BHA strongly reduces the amplitude of vibrations of the heme pocket environment. Unusually strong thermal broadening of the CO band above the glass transition is interpreted to be caused by thermal population of a very flexible excited conformational substate. The thermal broadening of the same band in the trehalose glass is caused by an increase of the protein vibrational amplitude in each of the conformational substates, their population being independent of the temperature in the glassy matrix.

Orientation distributions for cytochrome c on polar and nonpolar interfaces by total internal reflection fluorescence.

The formation of chemisorbed monolayers of yeast cytochrome c on both uncharged polar and nonpolar soft surfaces of organic self-assembled monolayers (SAM) on solid inorganic substrates was followed in situ by polarized total internal reflection fluorescence. Two types of nonpolar surfaces and one type of uncharged polar surface were used. The first type of nonpolar surface contained only thiol endgroups, while the other was composed of a mixture of thiol and methyl endgroups. The uncharged polar surface was provided by the mixture of thiol and hydroxyl endgroups. The thiol endgroups were used to form a covalent disulfide bond with the unique surface-exposed cysteine residue 102 of the protein. The mean tilt angle of the protein's zinc-substituted porphyrin was found to be 41 degrees and 50 degrees for the adsorption onto the nonpolar and uncharged polar surfaces, respectively. The distribution widths for the pure thiol and the thiol/methyl and thiol/hydroxyl mixtures were 9 degrees, 1 degrees, and 18 degrees, respectively. The high degree of the orientational order and good stability achieved for the protein monolayer on the mixed thiol/methyl endgroup SAM makes this system very attractive for studies of both intramolecular and intermolecular electron transfer processes.