ABSTRACT
OBJECTIVES: Homelessness is both a significant determinant and consequence of health and social inequalities. To better meet healthcare needs, dedicated mental health and general nurses were implemented to deliver outreach healthcare to people experiencing homelessness in one United Kingdom (UK) county. During COVID-19, the UK Government also instructed local authorities to accommodate individuals sleeping rough and have a national target to end rough sleeping. This qualitative study explored experiences of this nurse-let outreach service and housing journeys during and beyond COVID-19 among people experiencing homelessness. STUDY DESIGN: Face-to-face, narrative storytelling interviews were conducted via opportunistic sampling in community settings. Individuals with recent or current experiences of homelessness were eligible. METHODS: Participants were informed about the study via known professionals and introduced to the researcher. Eighteen narrative interviews were conducted, transcribed, and analysed using reflective thematic analysis. RESULTS: Individuals described complex journeys in becoming and being homeless. The nurse-led outreach service provided integral support, with reported benefits to person-centred and accessible care and improved outcomes in health and well-being. After being housed, individuals valued housing necessities and described new responsibilities. However, some participants did not accept or stay in housing provisions where they perceived risks. CONCLUSIONS: Interviewed participants perceived that the dedicated nurse-led outreach service improved their access to care and health outcomes. In the absence of dedicated provisions, mainstream healthcare should ensure flexible processes and collaborative professional working. Local authorities must also be afforded increased resources for housing, as well as integrated support, to reduce social and health inequalities.
Subject(s)
COVID-19 , Ill-Housed Persons , Humans , Housing , Delivery of Health Care , Mental Health , COVID-19/epidemiologyABSTRACT
BACKGROUND AND PURPOSE: The choroid plexus (CP) within the brain ventricles is well-known to produce cerebrospinal fluid (CSF). Recently, the CP has been recognized as critical in modulating inflammation. MRI-measured CP enlargement has been reported in neuroinflammatory disorders like MS as well as with aging and neurodegeneration. The basis of MRI-measured CP enlargement is unknown. On the basis of tissue studies demonstrating CP calcification as a common pathology associated with aging and disease, we hypothesized that previously unmeasured CP calcification contributes to MRI-measured CP volume and may be more specifically associated with neuroinflammation. MATERIALS AND METHODS: We analyzed 60 subjects (43 healthy controls and 17 subjects with Parkinson's disease) who underwent PET/CT using 11C-PK11195, a radiotracer sensitive to the translocator protein expressed by activated microglia. Cortical inflammation was quantified as nondisplaceable binding potential. Choroid plexus calcium was measured via manual tracing on low-dose CT acquired with PET and automatically using a new CT/MRI method. Linear regression assessed the contribution of choroid plexus calcium, age, diagnosis, sex, overall volume of the choroid plexus, and ventricle volume to cortical inflammation. RESULTS: Fully automated choroid plexus calcium quantification was accurate (intraclass correlation coefficient with manual tracing = .98). Subject age and choroid plexus calcium were the only significant predictors of neuroinflammation. CONCLUSIONS: Choroid plexus calcification can be accurately and automatically quantified using low-dose CT and MRI. Choroid plexus calcification-but not choroid plexus volume-predicted cortical inflammation. Previously unmeasured choroid plexus calcium may explain recent reports of choroid plexus enlargement in human inflammatory and other diseases. Choroid plexus calcification may be a specific and relatively easily acquired biomarker for neuroinflammation and choroid plexus pathology in humans.
Subject(s)
Microglia , Neuroinflammatory Diseases , Humans , Calcium , Positron Emission Tomography Computed Tomography , Magnetic Resonance Imaging , InflammationABSTRACT
BACKGROUND: Up to a quarter of inpatients in high-income countries (HICs) self-report beta-lactam allergy (BLA), which if incorrect,increases the use of alternative antibiotics, worsening individual health outcomes and driving bacterial resistance. In HICs, up to 95% ofself-reported BLAs are incorrect. The epidemiology of BLA in low- and middle-income African countries is unknown. OBJECTIVES: To describe the epidemiology and de-labelling outcomes of self-reported BLA in hospitalised South African (SA) patients. METHODS: Point-prevalence surveys were conducted at seven hospitals (adult, paediatric, government and privately funded, district andtertiary level) in Cape Town, SA, between April 2019 and June 2021. Ward prescription records and in-person interviews were conductedto identify and risk-stratify BLA patients using the validated PEN-FAST tool. De-labelling was attempted at the tertiary allergy clinic atGroote Schuur Hospital. RESULTS: A total of 1 486 hospital inpatients were surveyed (1 166 adults and 320 children). Only 48 patients (3.2%) self-reported a BLA,with a higher rate in private than in government-funded hospitals (6.3% v. 2.8%; p=0.014). Using the PEN-FAST tool, only 10.4% (n=5/48)of self-reported BLA patients were classified as high risk for true penicillin hypersensitivity. Antibiotics were prescribed to 70.8% (n=34/48)of self-reported BLA patients, with 64.7% (n=22/34) receiving a beta-lactam. Despite three attempts to contact patients for de-labelling atthe allergy clinic, only 3/36 underwent in vivo testing, with no positive results, and 1 patient proceeded to a negative oral challenge. CONCLUSION: Unlike HICs, self-reported BLA is low among inpatients in SA. The majority of those who self-reported BLA were low risk fortype 1 hypersensitivity, but outpatient de-labelling efforts were largely unsuccessful.
Subject(s)
Drug Hypersensitivity , Hypersensitivity , Adult , Humans , Child , beta-Lactams/adverse effects , Self Report , South Africa/epidemiology , Skin Tests/methods , Anti-Bacterial Agents/adverse effects , Penicillins , Drug Hypersensitivity/epidemiology , Hospitals, Public , Hospitals, Private , GovernmentSubject(s)
Anosmia , COVID-19 , Humans , Post-Acute COVID-19 Syndrome , COVID-19/complications , Muscle Weakness/etiologyABSTRACT
INTRODUCTION: Syngnathids (seahorses, pipefishes and seadragons) are among the few vertebrates that display male pregnancy. During seahorse pregnancy, males incubate developing embryos embedded in a placenta within a fleshy brood pouch, before expelling fully developed neonates at parturition. The mechanisms underpinning seahorse parturition are poorly understood. METHODS: We examined the morphology of the brood pouch using microcomputed tomography and histological techniques, in combination with physiological assays, to examine how male pot-bellied seahorses (Hippocampus abdominalis) control labour. In female-pregnant vertebrates, nonapeptide hormones (such as vasopressin- and oxytocin-like hormones) produce contractions of gestational smooth muscle to produce labour. RESULTS: Histological analysis of the seahorse brood pouch reveals only scattered small smooth muscle bundles in the brood pouch, and in-vitro application of isotocin (a teleost nonapeptide hormone) to the brood pouch do not produce measurable muscle contractions. Micro-computed tomography shows differences in size and orientation of the anal fin assembly between male and female pot-bellied seahorses, and histological analysis reveals large skeletal muscle bundles attached to the anal fin bones at the male brood pouch opening. DISCUSSION: We conclude that seahorse parturition may be facilitated by contraction of these muscles, which, in combination with body movements, serves to gape open the pouch and expel the neonates. Future biomechanical studies are needed to test this hypothesis.
Subject(s)
Smegmamorpha , Animals , Delivery, Obstetric , Female , Hormones , Humans , Infant, Newborn , Male , Parturition , Pregnancy , Smegmamorpha/anatomy & histology , Smegmamorpha/physiology , X-Ray MicrotomographyABSTRACT
Longitudinal alterations of gamma-aminobutyric acid (GABAA) receptor availability following traumatic brain injury have remained uncharacterized and may reflect changes in neuronal structure and function linked to cognitive recovery. We measured GABAA receptor availability using the tracer [11C]flumazenil in nine adults with traumatic brain injury (3-6 months after injury, subacute scan) and in 20 non-brain-injured individuals. A subset of subjects with traumatic brain injury (n = 7) were scanned at a second chronic time-point, 7-13 months after their first scan; controls (n = 9) were scanned for a second time, 5-11 months after the first scan. After accounting for atrophy in subjects with traumatic brain injury, we find broad decreases in GABAA receptor availability predominantly within the frontal lobes, striatum, and posterior-medial thalami; focal reductions were most pronounced in the right insula and anterior cingulate cortex (p < 0.05). Greater relative increase, compared to controls, in global GABAA receptor availability appeared between subacute and chronic scans. At chronic scan (>1 year post-injury), we find increased pallidal receptor availability compared to controls. Conversely, receptor availability remained depressed across the frontal cortices. Longitudinal improvement in executive attention correlated with increases in receptor availability across bilateral fronto-parietal cortical regions and the anterior-lateral aspects of the thalami. The specific observations of persistent bi-frontal lobe reductions and bilateral pallidal elevation are consistent with the anterior forebrain mesocircuit hypothesis for recovery of consciousness following a wide range of brain injuries; our results provide novel correlative data in support of specific cellular mechanisms underlying persistent cognitive deficits. Collectively, these measurements support the use of [11C]flumazenil to track recovery of large-scale network function following brain injuries and measure response to therapeutics.
ABSTRACT
INTRODUCTION: More than 30 million adults are released from incarceration globally each year. Many experience complex physical and mental health problems, and are at markedly increased risk of preventable mortality. Despite this, evidence regarding the global epidemiology of mortality following release from incarceration is insufficient to inform the development of targeted, evidence-based responses. Many previous studies have suffered from inadequate power and poor precision, and even large studies have limited capacity to disaggregate data by specific causes of death, sub-populations or time since release to answer questions of clinical and public health relevance. OBJECTIVES: To comprehensively document the incidence, timing, causes and risk factors for mortality in adults released from prison. METHODS: We created the Mortality After Release from Incarceration Consortium (MARIC), a multi-disciplinary collaboration representing 29 cohorts of adults who have experienced incarceration from 11 countries. Findings across cohorts will be analysed using a two-step, individual participant data meta-analysis methodology. RESULTS: The combined sample includes 1,337,993 individuals (89% male), with 75,795 deaths recorded over 9,191,393 person-years of follow-up. CONCLUSIONS: The consortium represents an important advancement in the field, bringing international attention to this problem. It will provide internationally relevant evidence to guide policymakers and clinicians in reducing preventable deaths in this marginalized population. KEY WORDS: Mortality; incarceration; prison; release; individual participant data meta-analysis; consortium; cohort.
ABSTRACT
We report a coherent mid-infrared (MIR) source with a combination of broad spectral coverage (6-18 µm), high repetition rate (50 MHz), and high average power (0.5 W). The waveform-stable pulses emerge via intrapulse difference-frequency generation (IPDFG) in a GaSe crystal, driven by a 30-W-average-power train of 32-fs pulses spectrally centered at 2 µm, delivered by a fiber-laser system. Electro-optic sampling (EOS) of the waveform-stable MIR waveforms reveals their single-cycle nature, confirming the excellent phase matching both of IPDFG and of EOS with 2-µm pulses in GaSe.
ABSTRACT
An experimental study into the modal dynamics of a short cavity, fast frequency-swept laser is presented. This commercially available external cavity swept source is designed for use in optical coherence tomography (OCT) applications and displays a number of dynamic lasing regimes during the course of the wavelength sweep. Interferometric full electric field reconstruction is employed, allowing for measurement of the laser operation in a time-resolved, single-shot manner. Recovery of both the phase and intensity of the laser output across the entire sweep enables direct visualization of the laser instantaneous optical spectrum. The electric field reconstruction technique reveals the presence of multi-mode dynamics, including coherent mode-locked pulses. During the main part of the imaging sweep, the laser is found to operate in a second harmonic sliding frequency mode-locking regime. Examination of the modal evolution of this coherent regime reveals evidence of previously unobserved frequency switching dynamics.
ABSTRACT
We report on the generation of a high-power frequency comb in the 2 µm wavelength regime featuring high amplitude and phase stability with unprecedented laser parameters, combining 60 W of average power with <30 fs pulse duration. The key components of the system are a mode-locked Er:fiber laser, a coherence-preserving nonlinear broadening stage, and a high-power Tm-doped fiber chirped-pulse amplifier with subsequent nonlinear self-compression of the pulses. Phase locking of the system resulted in a phase noise of less than 320 mrad measured within the 10 Hz-30 MHz band and 30 mrad in the band from 10 Hz to 1 MHz.
ABSTRACT
Novel species of fungi described in this study include those from various countries as follows: Australia: Banksiophoma australiensis (incl. Banksiophoma gen. nov.) on Banksia coccinea, Davidiellomycesaustraliensis (incl. Davidiellomyces gen. nov.) on Cyperaceae, Didymocyrtis banksiae on Banksia sessilis var. cygnorum, Disculoides calophyllae on Corymbia calophylla, Harknessia banksiae on Banksia sessilis, Harknessia banksiae-repens on Banksia repens, Harknessia banksiigena on Banksia sessilis var. cygnorum, Harknessia communis on Podocarpus sp., Harknessia platyphyllae on Eucalyptus platyphylla, Myrtacremonium eucalypti (incl. Myrtacremonium gen. nov.) on Eucalyptus globulus, Myrtapenidiella balenae on Eucalyptus sp., Myrtapenidiella eucalyptigena on Eucalyptus sp., Myrtapenidiella pleurocarpae on Eucalyptuspleurocarpa, Paraconiothyrium hakeae on Hakea sp., Paraphaeosphaeria xanthorrhoeae on Xanthorrhoea sp., Parateratosphaeria stirlingiae on Stirlingia sp., Perthomyces podocarpi (incl. Perthomyces gen. nov.) on Podocarpus sp., Readeriella ellipsoidea on Eucalyptus sp., Rosellinia australiensis on Banksia grandis, Tiarosporella corymbiae on Corymbia calophylla, Verrucoconiothyriumeucalyptigenum on Eucalyptus sp., Zasmidium commune on Xanthorrhoea sp., and Zasmidium podocarpi on Podocarpus sp. Brazil: Cyathus aurantogriseocarpus on decaying wood, Perenniporia brasiliensis on decayed wood, Perenniporia paraguyanensis on decayed wood, and Pseudocercospora leandrae-fragilis on Leandrafragilis.Chile: Phialocephala cladophialophoroides on human toe nail. Costa Rica: Psathyrella striatoannulata from soil. Czech Republic: Myotisia cremea (incl. Myotisia gen. nov.) on bat droppings. Ecuador: Humidicutis dictiocephala from soil, Hygrocybe macrosiparia from soil, Hygrocybe sangayensis from soil, and Polycephalomyces onorei on stem of Etlingera sp. France: Westerdykella centenaria from soil. Hungary: Tuber magentipunctatum from soil. India: Ganoderma mizoramense on decaying wood, Hodophilus indicus from soil, Keratinophyton turgidum in soil, and Russula arunii on Pterigota alata.Italy: Rhodocybe matesina from soil. Malaysia: Apoharknessia eucalyptorum, Harknessia malayensis, Harknessia pellitae, and Peyronellaea eucalypti on Eucalyptus pellita, Lectera capsici on Capsicum annuum, and Wallrothiella gmelinae on Gmelina arborea.Morocco: Neocordana musigena on Musa sp. New Zealand: Candida rongomai-pounamu on agaric mushroom surface, Candida vespimorsuum on cup fungus surface, Cylindrocladiella vitis on Vitis vinifera, Foliocryphia eucalyptorum on Eucalyptus sp., Ramularia vacciniicola on Vaccinium sp., and Rhodotorula ngohengohe on bird feather surface. Poland: Tolypocladium fumosum on a caterpillar case of unidentified Lepidoptera.Russia: Pholiotina longistipitata among moss. Spain: Coprinopsis pseudomarcescibilis from soil, Eremiomyces innocentii from soil, Gyroporus pseudocyanescens in humus, Inocybe parvicystis in humus, and Penicillium parvofructum from soil. Unknown origin: Paraphoma rhaphiolepidis on Rhaphiolepsis indica.USA: Acidiella americana from wall of a cooling tower, Neodactylaria obpyriformis (incl. Neodactylaria gen. nov.) from human bronchoalveolar lavage, and Saksenaea loutrophoriformis from human eye. Vietnam: Phytophthora mekongensis from Citrus grandis, and Phytophthora prodigiosa from Citrus grandis. Morphological and culture characteristics along with DNA barcodes are provided.
ABSTRACT
A time-resolved study is presented of the single-mode and mode-switching dynamics observed in swept source vertical cavity surfing emitting lasers and swept wavelength short external cavity lasers. A self-delayed interferometric technique is used to experimentally measure the phase and intensity of these frequency swept lasers, allowing direct examination of the modal dynamics. Visualisation of the instantaneous optical spectrum reveals mode-hop free single mode lasing in the case of the vertical cavity laser, with a tuning rate of 6.3 GHz/ns. More complex mode-switching behaviour occurs in the external cavity laser, with the mode-hopping dynamics found to be dominated by the deterministic movement of the spectral filter. Evidence of transient multi-mode operation and mode-pulling is also presented.
ABSTRACT
Rotational grazing management is commonly recommended to improve persistence of legumes interseeded into bermudagrass, but impacts on animal performance are poorly understood. Steers (n = 365, BW = 249 ± 22.9 kg) grazed mixed alfalfa (Medicago sativa L.)/bermudagrass (Cynodon dactylon [L.] Pers.) pastures (n = 10; 1.6-ha) with either continuous grazing (CONT) or rotational grazing (ROT) management over 3 yr. Initial stocking rate was set at 6.25 steers/ha. When forage allowance of CONT became limiting in mid-July each year, 2 randomly selected steers were removed from all pastures to maintain equal stocking rates in CONT and ROT. Rotational grazing pastures were divided into 8 paddocks with 3-d grazing and 21-d rest between grazing events. Initial, final, and interim (28-d) BW were collected following a 16-h removal from feed and water. Data were analyzed as a repeated measures experiment with completely random design using the mixed procedure of SAS (SAS Inst. Inc., Cary, NC) using pasture within treatment by year in the random statement. Across years, steer BW did not differ (P ≥ 0.47) at the midpoint or end of the grazing season. Daily BW gains during the early summer period tended (P = 0.10) to be 0.11 kg greater for CONT than ROT in yr 1, but did not differ (P ≥ 0.24) in yr 2 and 3. In the late summer, ADG was 0.15 kg less (P < 0.01) for CONT than ROT in yr 1, were not different (P = 0.23) in yr 2, and were 0.29 kg less (P < 0.01) for CONT than ROT in yr 3. Over the entire experimental period, ADG did not differ (P ≥ 0.67) in yr 1 or 2, but tended (P = 0.09) to be 0.10 kg greater for ROT than CONT in yr 3. Forage mass of ROT was greater (P < 0.01) than CONT throughout the grazing season. Because stocking rates were maintained at the same level, ROT pastures provided greater (P < 0.01) forage allowance during the grazing season than CONT explaining differences in ADG between treatments. Alfalfa stand percentage did not differ (P = 0.79) at the beginning of the experiment, but was less (P ≤ 0.03) for CONT than ROT at all other sampling dates. These data indicate that at equal stocking rates, ROT can maintain greater alfalfa persistence, forage nutritive quality, and forage allowance compared with continuous grazing and provided increased animal performance during the late summer when the alfalfa stand was reduced in CONT pastures.
Subject(s)
Animal Feed/analysis , Animal Husbandry/methods , Cattle/physiology , Cynodon , Medicago sativa , Animals , Cattle/growth & development , Male , Nutritive Value , Random Allocation , SeasonsABSTRACT
BACKGROUND AND AIMS: Obesity and cardiac left ventricular hypertrophy (LVH) are recognised independent risk factors in the development of heart failure (HF). However, the combination of these factors may exacerbate the onset of cardiovascular disease by mechanisms as yet unclear. LVH leads to significant cellular remodelling, including alterations in metabolism which may result in an inappropriate accumulation of lipids and eventual lipotoxicity and apoptosis. The aim of the study was to determine the impact of dietary manipulation on cardiac metabolism in the obese and hypertrophied heart. METHODS AND RESULTS: LVH was induced via aortic constriction (AC) in an experimental model of cardiac hypertrophy and animals subjected to 9 weeks of dietary manipulation with either a standard, high fat, or a sucrose containing Western-style diet (SD, HFD and WD, respectively). This latter diet resulted in accelerated weight gain in both LVH/AC and control animals. LVH was greater in AC animals fed a WD, and both control and AC animals from this diet showed a significant reduction in cardiac fatty acid oxidation and increased triacylglycerol content. Ceramide content was significantly increased in the WD groups, with no additional effect of LVH. Comparison with a model of HF induced by exposure to Doxorubicin and WD showed exacerbated remodelling of cardiac ceramide species leading to increased C16 and C18 content. CONCLUSIONS: These findings highlight the inappropriate accumulation and re-distribution of cardiac ceramide species in a diet-induced model of obesity and LVH, potentially increasing susceptibility to cell death. The combination of increased fat and sugar leads to greater pathological remodelling and may explain why this diet pattern is consistently linked with poor cardiovascular outcomes.
Subject(s)
Ceramides/metabolism , Diet, Western , Hypertrophy, Left Ventricular/metabolism , Myocardium/metabolism , Obesity/metabolism , Animals , Diet, High-Fat , Dietary Sucrose , Disease Models, Animal , Doxorubicin , Fatty Acids/metabolism , Heart Failure/chemically induced , Heart Failure/metabolism , Heart Failure/pathology , Hypertrophy, Left Ventricular/etiology , Hypertrophy, Left Ventricular/pathology , Male , Myocardium/pathology , Obesity/etiology , Obesity/pathology , Oxidation-Reduction , Rats, Sprague-Dawley , Time Factors , Triglycerides/metabolism , Up-RegulationABSTRACT
BACKGROUND: Delayed graft function (DGF) is defined as the need for dialysis within 1 week of transplantation and occurs in 20%-50% of deceased-donor kidney transplant recipients. Although recovery from DGF often occurs within a few days, many cases may take weeks to months before the transplant function begins. The delay in function increases the complexity of recipient care, makes the diagnosis of acute rejection more difficult, prolongs length of stay, and increases hospital costs. Although several authors have proposed nomograms to predict DGF, there is no identifiable strategy to ameliorate it, except for the possible use of a specific type of induction therapy called Thymoglobulin. METHODS: In this retrospective analysis we included 407 subjects, of which 76 were mated (left and right kidney transplanted at Montefiore from the same donor). We used conditional logistic regression analysis while adjusting for the mated kidneys. We adjusted for age, gender, and race a priori, as well as cold ischemia time. RESULTS: There was a 36% decrease in odds of DGF when Thymoglobulin was used as induction when compared with basiliximab in mated kidneys 0.64 (0.10-4.05) (odds ratio [OR] with 95% confidence interval [CI]). CONCLUSIONS: Thymoglobulin did have a protective effect in these data when analyzed in mated kidneys, however, we need a larger amount of data to concretely conclude this effect.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Antilymphocyte Serum/therapeutic use , Delayed Graft Function/prevention & control , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , Recombinant Fusion Proteins/therapeutic use , Adult , Aged , Basiliximab , Female , Humans , Induction Chemotherapy , Logistic Models , Male , Middle Aged , Retrospective Studies , Treatment OutcomeABSTRACT
Shprintzen-Goldberg syndrome (SGS) is an autosomal dominant connective tissue disorder. To date, this report is the first account of a successful pancreas transplantation from an SGS donor. The similarity of the outcomes from previous year-on-year pancreas transplantations at the same center demonstrates promising results. Increasing awareness of the utilization of donors with SGS may promote expansion of center-specific criteria for organ acceptance. Therefore, every consideration should be given for use of organs from donors with this genetic abnormality because there is no evidence to suggest poorer allograft viability.
Subject(s)
Arachnodactyly , Craniosynostoses , Marfan Syndrome , Pancreas Transplantation , Tissue Donors , Adolescent , Adult , Blood Glucose/analysis , Diabetes Mellitus, Type 1/surgery , Diabetic Nephropathies/surgery , Female , Humans , Kidney Transplantation , MaleABSTRACT
The central nervous system is functionally organized as a dynamic network of interacting neural circuits that underlies observable behaviors. At higher resolution, these behaviors, or phenotypes, are defined by the activity of a specific set of biomolecules within those circuits. Identification of molecules that govern psychiatric phenotypes is a major challenge. The only organic molecular entities objectively associated with psychiatric phenotypes in humans are drugs that induce psychiatric phenotypes and drugs used for treatment of specific psychiatric conditions. Here, we identified candidate biomolecules contributing to the organic basis for psychosis by deriving an in vivo biomolecule-tissue signature for the atypical pharmacologic action of the antipsychotic drug clozapine. Our novel in silico approach identifies the ensemble of potential drug targets based on the drug's chemical structure and the region-specific gene expression profile of each target in the central nervous system. We subtracted the signature of the action of clozapine from that of a typical antipsychotic, chlorpromazine. Our results implicate dopamine D4 receptors in the pineal gland and muscarinic acetylcholine M1 (CHRM1) and M3 (CHRM3) receptors in the prefrontal cortex (PFC) as significant and unique to clozapine, whereas serotonin receptors 5-HT2A in the PFC and 5-HT2C in the caudate nucleus were common significant sites of action for both drugs. Our results suggest that D4 and CHRM1 receptor activity in specific tissues may represent underappreciated drug targets to advance the pharmacologic treatment of schizophrenia. These findings may enhance our understanding of the organic basis of psychiatric disorders and help developing effective therapies.
Subject(s)
Antipsychotic Agents/metabolism , Brain/metabolism , Chlorpromazine/metabolism , Clozapine/metabolism , Receptor, Muscarinic M1/metabolism , Receptor, Muscarinic M3/metabolism , Receptor, Serotonin, 5-HT2A/metabolism , Receptor, Serotonin, 5-HT2C/metabolism , Receptors, Dopamine D4/metabolism , Caudate Nucleus/metabolism , Computer Simulation , Humans , Pineal Gland/metabolism , Prefrontal Cortex/metabolismABSTRACT
Prisoner populations are characterized by high rates of hepatitis C (HCV), up to thirty times that of the general population in Australia. Within Australian prisons, less than 1% of eligible inmates access treatment. Public health strategies informed by social capital could be important in addressing this inequality in access to HCV treatment. Twenty-eight male inmates participated in qualitative interviews across three correctional centres in New South Wales, Australia. All participants had recently tested as HCV RNA positive or were receiving HCV treatment. Analysis was conducted with participants including men with experiences of HCV treatment (n=10) (including those currently accessing treatment and those with a history of treatment) and those who were treatment naïve (n=18). Social capital was a resourceful commodity for inmates considering and undergoing treatment while in custody. Inmates were a valuable resource for information regarding HCV treatment, including personal accounts and reassurance (bonding social capital), while nurses a resource for the provision of information and care (linking social capital). Although linking social capital between inmates and nurses appeared influential in HCV treatment access, there remained opportunities for increasing linking social capital within the prison setting (such as nurse-led engagement within the prisons). Bonding and linking social capital can be valuable resources in promoting HCV treatment awareness, uptake and adherence. Peer-based programmes are likely to be influential in promoting HCV outcomes in the prison setting. Engagement in prisons, outside of the clinics, would enhance opportunities for linking social capital to influence HCV treatment outcomes.
Subject(s)
Awareness , Health Knowledge, Attitudes, Practice , Hepatitis C/drug therapy , Patient Acceptance of Health Care , Prisons , Social Capital , Adolescent , Adult , Humans , Interviews as Topic , Male , Middle Aged , New South Wales , Prisoners , Young AdultABSTRACT
A simple method of high-speed random bit generation is presented that utilizes the turbulent output of a fiber ring cavity semiconductor laser. Random bits are generated by multi-bit sampling of the chaotic optical waveform passed through a simple post-processing procedure, leading to generation rates up to and potentially exceeding 1 Tb/s. The resulting random bit streams are tested statistically using a software package designed to test random number generators, the NIST statistical test suite. The bit streams pass each of these test sets, indicating their suitability for use in random number generation applications. This novel technique allows the generation of random bits from less complex experimental conditions than previously reported, while improving upon recent previous studies in terms of bit rate and quality of bits.
ABSTRACT
A novel, time-resolved interferometric technique is presented that allows the reconstruction of the complex electric field output of a swept source laser in a single-shot measurement. The power of the technique is demonstrated by examining a short cavity swept source designed for optical coherence tomography (OCT) applications with a spectral width of over 100 nm. The novel analysis allows a time-resolved real-time characterization of the roll-off, optical spectrum, linewidth, and coherence properties of a dynamic, rapidly swept laser source.