Rate of community treatment orders and readmission orders following reconfiguration of community mental health services.

OBJECTIVES: Community treatment orders (CTOs) are a controversial practice as they extend the practice of involuntary treatment into the community. This study aimed to determine whether there was a difference in the rate of CTOs and revocation (readmission) orders following the implementation of a recovery-orientated model across four adult mental health services. METHODS: A retrospective cohort study was conducted prior to and after the reconfiguration of services. Population data for those aged 15 to 65 were obtained from a census and rate rates were calculated. RESULTS: Prior to the reconfiguration, there were 893 individuals subject to a CTO and 136 of these individuals had a revocation of their CTO (i.e. were involuntarily readmitted). This represented a rate of 100.8 individuals on CTOs per 100,000 population and a rate of 15.4 revocations per 100,000 population. Following the reconfiguration, the rate of CTOs increased by 10% and there was a trend for the rate of revocation orders to have decreased by 17%. CONCLUSIONS: Rates of CTOs and readmissions varied across services and further research is warranted to identify factors associated with these increased rates. Additionally, the very high rate of CTOs in the catchment areas warrants further examination.

Succinimidyl ester surface chemistry: implications of the competition between aminolysis and hydrolysis on covalent protein immobilization.

N-Hydroxysuccinimide (NHS) ester terminal groups are commonly used to covalently couple amine-containing biomolecules (e.g., proteins and peptides) to surfaces via amide linkages. This one-step aminolysis is often performed in buffered aqueous solutions near physiological pH (pH 6 to pH 9). Under these conditions, the hydrolysis of the ester group competes with the amidization process, potentially degrading the efficiency of the coupling chemistry. The work herein examines the efficiency of covalent protein immobilization in borate buffer (50 mM, pH 8.50) using the thiolate monolayer formed by the chemisorption of dithiobis (succinimidyl propionate) (DSP) on gold films. The structure and reactivity of these adlayers are assessed via infrared spectroscopy (IR), X-ray photoelectron spectroscopy (XPS), electrochemical reductive desorption, and contact angle measurements. The hydrolysis of the DSP-based monolayer is proposed to follow a reaction mechanism with an initial nucleation step, in contrast to a simple pseudo first-order reaction rate law for the entire reaction, indicating a strong dependence of the interfacial reaction on the packing and presence of defects in the adlayer. This interpretation is used in the subsequent analysis of IR-ERS kinetic plots which give a heterogeneous aminolysis rate constant, ka, that is over 3 orders of magnitude lower than that of the heterogeneous hydrolysis rate constant, kh. More importantly, a projection of these heterogeneous kinetic rates to protein immobilization suggests that under coupling conditions in which low protein concentrations and buffers of near physiological pH are used, proteins are more likely physically adsorbed rather than covalently linked. This result is paramount for biosensors that use NHS chemistry for protein immobilization due to effects that may arise from noncovalently linked proteins.

Revocation of Community Treatment Orders in a mental health service network.

OBJECTIVE: Community Treatment Orders (CTOs) require patients to co-operate with involuntary treatment in the community or risk having their CTO revoked and being readmitted to hospital. CTOs are used frequently in Australia. Their revocation has been under-investigated but is important because of the significant impact this process has on patients, families/carers and service-providers. This paper reports on an investigation of CTO revocations in a Victorian area mental health service in the period 2008-2010. METHOD: This was a mixed-methods study involving extraction of data from the Victorian statewide clinical database, a file audit and semi-structured group interviews with key stakeholders. Two different time periods were compared. RESULTS: CTOs are commonly revoked within three months of discharge from the inpatient unit and multiple service-providers and family/carers have varying involvement that appears to depend on the timing of the referral to the Crisis Assessment and Treatment Team. CONCLUSIONS: The study identified opportunities for improving policy and practice, particularly in relation to reducing the amount of coercion experienced by people on CTOs and improving flexibility of service delivery.

Detection of the tuberculosis biomarker mannose-capped lipoarabinomannan in human serum: Impact of sample pretreatment with perchloric acid.

The development of an accurate and rapid diagnostic test for tuberculosis (TB) to use at point of need is vital to efforts aimed at reducing the global burden from this disease. This paper builds on our previous studies of mannose-capped lipoarabinomannan (ManLAM) as a serum biomarker for active TB infection by means of a heterogeneous immunoassay. That work found that complexation with components in serum (e.g., proteins) sterically hindered the capture and/or labeling of ManLAM in an immunoassay at levels <10 ng mL-1, compromising the clinical utility of this biomarker for detection of active TB infection. We also showed that the acidification of ManLAM-containing serum samples with perchloric acid improved the detectability of ManLAM by 250× by complex disruption when compared to measurements of untreated serum. The present study examined what effects the PCA treatment of serum samples may have on the recovery and structural integrity of ManLAM, owing to its potential susceptibility to acid hydrolysis. Recovery was assessed with an enzyme-linked immunosorbent assay (ELISA). The possible impact of acid hydrolysis on the ManLAM structure was investigated by gas chromatography-mass spectrometry and carbohydrate chemical degradation methods. The ELISA study indicated that while the signal strength for ManLAM in the serum spike-in experiments was significantly stronger after PCA pretreatment when compared to untreated human serum, it was only ∼20% of the ManLAM measured in physiological buffer. This loss in detectability was shown by structural analysis to arise mainly from the acid-induced degradation of the arabinan domains of ManLAM that are targeted by antibodies used for antigen capture and/or tagging. The implications of these findings in terms of the detection of this important biomarker for TB are also discussed.

Handheld Raman Spectrometer Instrumentation for Quantitative Tuberculosis Biomarker Detection: A Performance Assessment for Point-of-Need Infectious Disease Diagnostics.

Techniques for the detection of disease biomarkers are key components in the protection of human health. While work over the last few decades has redefined the low-level measurement of disease biomarkers, the translation of these capabilities from the formal clinical setting to point-of-need (PON) usage has been much more limited. This paper presents the results of experiments designed to examine the potential utility of a handheld Raman spectrometer as a PON electronic reader for a sandwich immunoassay based on surface-enhanced Raman scattering (SERS). In so doing, the study herein used a recently developed procedure for the SERS detection of phospho-myo-inositol-capped lipoarabinomannan (PILAM) as a means to compare the performance of laboratory-grade and handheld instrumentation and, therefore, gauge the utility of the handheld instrument for PON deployment. Phospho-myo-inositol-capped lipoarabinomannan is a non-pathogenic simulant for mannose-capped lipoarabinomannan (ManLAM), which is an antigenic marker found in serum and other body fluids of individuals infected with tuberculosis (TB). The results of the measurements with the field-portable spectrometer were then compared to those obtained for the same samples when using a much more sensitive benchtop Raman spectrometer. The results, albeit under different operational settings for the two spectrometers (e.g., signal integration time), are promising in that the limit of detection found for PILAM spiked in human serum when using the handheld system (0.18 ng/mL) approached that of the benchtop instrument (0.032 ng/mL). This work also: (1) identified potential adaptations (e.g., optimization of the plasmonically enhanced response for measurement by the handheld unit through a change in the excitation wavelength) to tighten the gap in performance; and (2) briefly examined the next steps and potential processes required to move this immunoassay platform closer to PON utility.

Clinical Pharmacist Faculty Contribution to Evidence-Based Medicine and Milestones.

INTRODUCTION: Family medicine residency programs (FMRPs) endeavor to meet evidence-based medicine (EBM) subcompetencies through the milestones project. Comprehensive descriptions of clinical pharmacists' contributions in teaching EBM within the context of residency are limited. METHODS: Over a study period of 2 months, clinical pharmacists across five FMRPs in four states were invited to track their interactions with physician residents. EBM resources, skills, and targeted milestone data were collected. Pharmacists also quantified their nonpatient care contributions to EBM. RESULTS: Of the 16 clinical pharmacists invited, 16 (100%) participated in the October and 12 (75.0%) in the March collection period. A total of 598.9 half days over 2 months (42 working days) of available teaching time were reported. The tracking tool captured 1,253 EBM teaching encounters with a total average of 2.1 encounters per half day. Of those encounters, point-of-care references were most commonly used (63.7%) and "apply" was the most common EBM skill taught (83.8%). The most commonly tracked milestone was Medical Knowledge 2 (75.3%) at Level 2. Nine out of 10 faculty pharmacists included in this study reported performing the following roles: preceptor (100%), lecturer (89.9%), provider (77.8%), expert/consultant (77.8%), health care team (66.7%), and other (11.1%). Faculty pharmacists also reported directly evaluating milestones for physician residents through: committee work (44.4%), resident evaluations (77.8%), and rotation evaluations (77.8%). CONCLUSIONS: As FMRPs strive to meet ACGME EBM-related competencies, clinical pharmacists across multiple sites demonstrated contributions to teaching EBM in medical resident education. Using a nonphysician faculty for this purpose may provide an example for other FMRPs.

Advantages and limitations of nanoparticle labeling for early diagnosis of infection.

INTRODUCTION: Nanoparticle-based disease diagnostics harness a range of unique physical and chemical phenomena for the detection of biomarkers at exceedingly low levels. This capability potentially enables the diagnosis of disease earlier in its progression and improves the likelihood of positive treatment outcomes. This review highlights recent work in this area, and then projects the next steps needed to move this emerging capability beyond the research laboratory. AREAS COVERED: This review examines the advantages and limitations of in vitro health care diagnostic tests that utilize nanoparticles (e.g. noble metal, quantum dot, and magnetic). It includes a brief overview of their unique properties, syntheses, and applicable readout strategies. This is followed by a brief synopsis of the obstacles faced when attempting to translate nanoparticle-based diagnostics from the R&D laboratory to the clinic and other arenas (i.e. the difficulties common to in vitro diagnostics), and then by a much more in-depth examination of the need to control and characterize a range of nanoparticle properties (e.g. size, shape, surface composition, and stability) when making this transition. Expert commentary: The review wraps up with a short commentary and perspective for the next five years, focusing on possible guidelines for nanoparticle characterization.

gbpA as a Novel qPCR Target for the Species-Specific Detection of Vibrio cholerae O1, O139, Non-O1/Non-O139 in Environmental, Stool, and Historical Continuous Plankton Recorder Samples.

The Vibrio cholerae N-acetyl glucosamine-binding protein A (GbpA) is a chitin-binding protein involved in V. cholerae attachment to environmental chitin surfaces and human intestinal cells. We previously investigated the distribution and genetic variations of gbpA in a large collection of V. cholerae strains and found that the gene is consistently present and highly conserved in this species. Primers and probe were designed from the gbpA sequence of V. cholerae and a new Taq-based qPCR protocol was developed for diagnostic detection and quantification of the bacterium in environmental and stool samples. In addition, the positions of primers targeting the gbpA gene region were selected to obtain a short amplified fragment of 206 bp and the protocol was optimized for the analysis of formalin-fixed samples, such as historical Continuous Plankton Recorder (CPR) samples. Overall, the method is sensitive (50 gene copies), highly specific for V. cholerae and failed to amplify strains of the closely-related species Vibrio mimicus. The sensitivity of the assay applied to environmental and stool samples spiked with V. cholerae ATCC 39315 was comparable to that of pure cultures and was of 102 genomic units/l for drinking and seawater samples, 101 genomic units/g for sediment and 102 genomic units/g for bivalve and stool samples. The method also performs well when tested on artificially formalin-fixed and degraded genomic samples and was able to amplify V. cholerae DNA in historical CPR samples, the earliest of which date back to August 1966. The detection of V. cholerae in CPR samples collected in cholera endemic areas such as the Benguela Current Large Marine Ecosystem (BCLME) is of particular significance and represents a proof of concept for the possible use of the CPR technology and the developed qPCR assay in cholera studies.

The large capacity for dark nitrate-assimilation in diatoms may overcome nitrate limitation of growth.

• The ability of the diatom Thalassiosira weissflogii to assimilate inorganic N in darkness is compared with that seen in flagellates. • Experiments were conducted with T. weissflogii grown in N-replete and in N-limiting cultures and the rates and capacity for ammonium and nitrate assimilation were determined. • High daily growth rates in the diatom under high-light nitrate-replete conditions are only attainable by continuing nitrate assimilation in darkness using excess C accumulated in the light when nitrate assimilation cannot match C-fixation. The ability to use ammonium in darkness is greater than for nitrate but the ratio of dark to light assimilation for each N source is similar over a wide range of cellular N : C ratios. These capabilities are in strong contrast with those in the flagellates Heterosigma carterae and Heterocapsa illdefina, which are incapable of high nitrate use in darkness. • While the possession of large capacity for dark nitrate-assimilation in diatoms may provide a mechanism that overcomes nitrate limitation of growth, the explanation for the lower capabilities exhibited by flagellates is less clear.

Modelling suggests that optimization of dark nitrogen-assimilation need not be a critical selective feature in phytoplankton.

• Alternative strategies for the dark assimilation of ammonium and nitrate into microalgae are explored using a mechanistic model of algal physiology. • The standard diatom strategy, continuation of N assimilation at high rates in darkness as long as reserve C remains, is the most advantageous. The flagellate strategy, incorporating ammonium but not nitrate at a reasonable rate in darkness, is best suited to organisms with high metabolic costs, inhabiting waters with relatively high concentrations of ammonium. The strategy of vertically migrating diatoms - accumulation of nitrate in internal pools for assimilation after return to the photic zone - is best suited to slow-growing cells in low-ammonium environments. • Differences between the strategies become less significant with increasing N-source limitation (the situation more typically encountered by flagellates and migratory species) because transport rather than post-transport assimilatory processes become most limiting. • It is suggested that optimization of dark N-assimilation is not a critical selective feature; organisms with contrasting abilities in this regard usually inhabit different water bodies and have other more fundamental phenotypic differences (e.g. motility or silicon requirements).

Sustained UK marine observations. Where have we been? Where are we now? Where are we going?

This introduction traces the earliest interaction of ancient humans with their marine environment, through marine explorations in the Middle Ages and Renaissance, to the development of early marine science in the Enlightenment. This sets the scene for how marine observations developed in the modern era and explains the status of today's marine observation networks. The paper concludes with an assessment of the future needs and constraints of sustained marine observation networks and suggests the lessons from a long history might be the key to the future.

Bacterial diversity in the bacterioneuston (sea surface microlayer): the bacterioneuston through the looking glass.

The bacterioneuston is defined as the community of bacteria present within the neuston or sea surface microlayer. Bacteria within this layer were sampled using a membrane filter technique and bacterial diversity was compared with that in the underlying pelagic coastal seawater using molecular ecological techniques. 16S rRNA gene libraries of approximately 500 clones were constructed from both bacterioneuston and the pelagic water samples and representative clones from each library were sequenced for comparison of bacterial diversity. The bacterioneuston was found to have a significantly lower bacterial diversity than the pelagic seawater, with only nine clone types (ecotaxa) as opposed to 46 ecotaxa in the pelagic seawater library. Surprisingly, the bacterioneuston clone library was dominated by 16S rRNA gene sequences affiliated to two groups of organisms, Vibrio spp. which accounted for over 68% of clones and Pseudoalteromonas spp. accounting for 21% of the library. The dominance of these two 16S rRNA gene sequence types within the bacterioneuston clone library was confirmed in a subsequent gene probing experiment. 16S rRNA gene probes specific for these groups of bacteria were designed and used to probe new libraries of 1000 clones from both the bacterioneuston and pelagic seawater DNA samples. This revealed that 57% of clones from the bacterioneuston library hybridized to a Vibrio sp.-specific 16S rRNA gene probe and 32% hybridized to a Pseudoalteromonas sp.-specific 16S rRNA gene probe. In contrast, the pelagic seawater library resulted in only 13% and 8% of 16S rRNA gene clones hybridizing to the Vibrio sp. and Pseudoalteromonas sp. probes respectively. Results from this study suggest that the bacterioneuston contains a distinct population of bacteria and warrants further detailed study at the molecular level.

Seasonality of symptom onset in first-episode schizophrenia.

BACKGROUND: There have been numerous reports of seasonal trends in psychotic illnesses. In schizophrenia, seasonal trends in incidence have been shown to be especially apparent in first-episode cases. Most previous research has used date of admission as a proxy for date of incidence of disorder; we present results of an investigation into seasonal trends in dates of onset of symptoms in a group of 295 first-episode cases of schizophrenia and schizophreniform disorder. METHOD: Data were analysed using statistical methods appropriate for detecting seasonal trends in pooled data over 6 years. RESULTS: Only male cases of schizophrenia and schizophreniform disorder showed a significant seasonal distribution to dates of onset of symptoms, with a peak in August (winter). CONCLUSION: True seasonal patterns are present in schizophrenia incidence, but their consistency with other published studies and wider significance, is difficult to ascertain because of different methods used in dating incidence of disorder.

Evidence that health attributions and symptom severity predict insight in schizophrenia.

Although a relationship between insight and symptomatology in schizophrenia has been repeatedly demonstrated, the influence of psychological variables such as coping mechanisms and attributional style is less clear. We evaluated health attributions, subjective resources for coping, symptomatology, general cognitive functioning, and insight among 38 consecutive admissions with DSM-III-R schizophrenia from a geographically defined catchment area. Health attributions accounted for a significant amount of insight even after symptom severity was accounted for and together predicted 32% of variation in insight scores. This study emphasizes the multifactorial nature of insight and the importance of psychological variables in addition to symptomatology.

Compliance therapy: a randomised controlled trial in schizophrenia.

OBJECTIVE: To evaluate the efficacy of "compliance therapy" for improving adherence to prescribed drug treatment among patients with schizophrenia. DESIGN: Randomised controlled trial. SETTING: Urban catchment area psychiatric service. PARTICIPANTS: 94 consecutive admissions of patients with schizophrenia, 56 agreed to participate. INTERVENTION: Compliance therapy and non-specific counselling, each consisting of 5 sessions lasting 30-60 minutes. MAIN OUTCOME MEASURES: Compliance with drug treatment at one year; attitudes to treatment, symptomatology, insight, and quality of life at one year; length of "survival" in the community, bed days, and rehospitalisation rates at two years. RESULTS: Compliance therapy did not confer a major advantage over non-specific therapy in improving compliance at one year (43% (12/28) v 54% (15/28), difference -11% (95% confidence interval -37% to 15%) or in any of the secondary outcome measures-symptomatology, attitudes to treatment, insight, global assessment of functioning, and quality of life. CONCLUSION: Compliance therapy may not be of benefit to patients with schizophrenia. Attitudes to treatment at baseline predicted adherence one year later and may be a clinically useful tool.