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Frascati international research criteria for HIV-associated neurocognitive disorders (HAND) are controversial; some investigators have argued that Frascati criteria are too liberal, resulting in a high false positive rate. Meyer et al. recommended more conservative revisions to HAND criteria, including exploring other commonly used methodologies for neurocognitive impairment (NCI) in HIV including the global deficit score (GDS). This study compares NCI classifications by Frascati, Meyer, and GDS methods, in relation to neuroimaging markers of brain integrity in HIV.
Two hundred forty-one people living with HIV (PLWH) without current substance use disorder or severe (confounding) comorbid conditions underwent comprehensive neurocognitive testing and brain structural magnetic resonance imaging and magnetic resonance spectroscopy. Participants were classified using Frascati criteria versus Meyer criteria: concordant unimpaired [Frascati(Un)/Meyer(Un)], concordant impaired [Frascati(Imp)/Meyer(Imp)], or discordant [Frascati(Imp)/Meyer(Un)] which were impaired via Frascati criteria but unimpaired via Meyer criteria. To investigate the GDS versus Meyer criteria, the same groupings were utilized using GDS criteria instead of Frascati criteria.
When examining Frascati versus Meyer criteria, discordant Frascati(Imp)/Meyer(Un) individuals had less cortical gray matter, greater sulcal cerebrospinal fluid volume, and greater evidence of neuroinflammation (i.e., choline) than concordant Frascati(Un)/Meyer(Un) individuals. GDS versus Meyer comparisons indicated that discordant GDS(Imp)/Meyer(Un) individuals had less cortical gray matter and lower levels of energy metabolism (i.e., creatine) than concordant GDS(Un)/Meyer(Un) individuals. In both sets of analyses, the discordant group did not differ from the concordant impaired group on any neuroimaging measure.
The Meyer criteria failed to capture a substantial portion of PLWH with brain abnormalities. These findings support continued use of Frascati or GDS criteria to detect HIV-associated CNS dysfunction.
Background: SMA is characterized by reduced levels of survival of motor neuron (SMN) protein from deletions and/or mutations of the SMN1 gene. While SMN1 produces full-length SMN protein, a second gene, SMN2, produces low levels of functional SMN protein. Risdiplam (RG7916/RO7034067) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates pre-mRNA splicing of SMN2 to increase SMN protein levels. Methods: SUNFISH (NCT02908685) is an ongoing multicenter, double-blind, placebo-controlled, operationally seamless study (randomized 2:1, risdiplam:placebo) in patients aged 2–25 years, with Type 2/3 SMA. Part 1 (n=51) assesses safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels. Pivotal Part 2 (n=180) assesses safety and efficacy of the risdiplam dose level selected based on Part 1 results. Results: Part 1 results showed a sustained, >2-fold increase in median SMN protein versus baseline following 1 year of treatment. Adverse events were mostly mild, resolved despite ongoing treatment and reflected underlying disease. No drug-related safety findings have led to withdrawal (data-cut 06/17/18). SUNFISH Part 1 exploratory endpoint results and Part 2 study design will also be presented. Conclusions: To date, no drug-related safety findings have led to withdrawal. Risdiplam led to sustained increases in SMN protein levels.
Introduction: Acute migraine headaches are common causes of presentation to the emergency department (ED). There is great variability in the efficacy of the available parenteral agents to manage pain, though triptans are among the recommended treatments. The objective of this systematic review was to update a previous review examining the effectiveness of parenteral agents for the treatment of acute migraine in the ED or equivalent acute care setting; our review examined pain management in emergency settings and assessed the effectiveness of triptan agents. Methods: A comprehensive search of 10 electronic databases and grey literature was conducted to supplement the previous systematic review. Two independent reviewers completed study selection, quality assessment, and data extraction. Any discrepancies were resolved by third party adjudication. Pain scale scores were analyzed using standardized mean difference (SMD) with 95% confidence intervals (CIs) calculated using a random effects model; heterogeneity (I2) was reported. Results: Titles and abstracts of 5039 unique studies were reviewed, of which, 51 studies were included. Sixty-four studies from the original review were included, resulting in a total of 115 included studies. Pain was measured within the ED or equivalent acute care setting using a variety of pain scales, most commonly the 0-10 cm or 100 mm visual analog scale. Four studies compared pain scores between patients receiving sumatriptan vs. other agents, of which, patients receiving sumatriptan reported higher pain scale scores (SMD = 0.53; 95% CI: 0.04, 1.02; I2 = 80%). In particular, patients receiving sumatriptan reported higher pain scale scores than patients receiving metoclopramide (SMD = 0.68; 95% CI: 0.31, 1.04; n = 1) or ketorolac (SMD = 1.39; 95% CI: 0.56, 2.21; n = 1). Overall, studies comparing anti-inflammatory agents (i.e., ketorolac or dexketoprofen) to other agents reported improved pain scale scores among patients receiving anti-inflammatory agents (SMD = -0.38; 95% CI: -0.73, -0.03; I2 = 66%; n = 5). Conclusion: Limited evidence suggests that patients treated with metoclopramide or anti-inflammatory agents experience greater pain reduction compared to patients treated with sumatriptan. This review will conduct a network analysis of parenteral agents to examine the comparative effectiveness of parenteral agents to manage pain among patients with acute migraine. Further analysis will also consider the balance between efficacy and adverse events.
Introduction: Although a variety of parenteral agents exist for the treatment of acute migraine, relapse after an emergency department (ED) visit is still a common occurrence. The objective of this systematic review was to update a previous review examining the effectiveness of parenteral agents for the treatment of acute migraine in the ED or equivalent acute care setting; our review focused on those studies aiming a reduction in relapse after an ED visit. Methods: A comprehensive search of 10 electronic databases and grey literature was conducted to identify comparative studies to supplement the previous systematic review. Two independent reviewers completed study selection, quality assessment, and data extraction. Any discrepancies were resolved by third party adjudication. Relative risks (RR) with 95% confidence intervals (CIs) were calculated using a random effects model and heterogeneity (I2) was reported. Results: Titles and abstracts of 5039 unique studies were reviewed, of which, 51 studies were included. Sixty-four studies from the original review were included, resulting in a total of 115 included studies. Relapse was reported in 44 (38%) included studies and occurred commonly in patients receiving placebo or no interventions (median = 39%; IQR: 14%, 47%). Overall, no differences in headache relapse were found between patients receiving sumatriptan or placebo (RR = 1.09; 95% CI: 0.55, 2.17; I2 = 93%; n = 8). Conversely, patients receiving neuroleptic agents experienced fewer relapses compared to placebo (RR = 0.27; 95% CI: 0.12, 0.58; I2 = 0%; n = 3); however, patients receiving neuroleptics reported an increase in adverse events (RR = 1.87; 95% CI: 1.17, 3.00; I2 = 0%; n = 3). Compared to placebo, patients receiving dexamethasone were less likely to experience a headache recurrence (RR = 0.71; 95% CI: 0.53, 0.95; I2 = 60%, n = 9); however, no differences were found in reported adverse events (RR = 1.09; 95% CI: 0.81, 1.47; I2 = 0%; n = 3). Conclusion: Relapse is a common occurrence for patients with migraine headaches. This review found patients receiving neuroleptics or dexamethasone experienced fewer headache recurrences. Conversely, triptan agents appear to have minimal effect on reducing the risk for headache recurrence following discharge from an acute care setting. Limited available data on adverse events is an important limitation to inform decision-making. Guidelines should be revised to reflect these results.
Whereas genetic susceptibility increases the risk for major depressive disorder (MDD), non-genetic protective factors may mitigate this risk. In a large-scale prospective study of US Army soldiers, we examined whether trait resilience and/or unit cohesion could protect against the onset of MDD following combat deployment, even in soldiers at high polygenic risk.
Data were analyzed from 3079 soldiers of European ancestry assessed before and after their deployment to Afghanistan. Incident MDD was defined as no MDD episode at pre-deployment, followed by a MDD episode following deployment. Polygenic risk scores were constructed from a large-scale genome-wide association study of major depression. We first examined the main effects of the MDD PRS and each protective factor on incident MDD. We then tested the effects of each protective factor on incident MDD across strata of polygenic risk.
Polygenic risk showed a dose–response relationship to depression, such that soldiers at high polygenic risk had greatest odds for incident MDD. Both unit cohesion and trait resilience were prospectively associated with reduced risk for incident MDD. Notably, the protective effect of unit cohesion persisted even in soldiers at highest polygenic risk.
Polygenic risk was associated with new-onset MDD in deployed soldiers. However, unit cohesion – an index of perceived support and morale – was protective against incident MDD even among those at highest genetic risk, and may represent a potent target for promoting resilience in vulnerable soldiers. Findings illustrate the value of combining genomic and environmental data in a prospective design to identify robust protective factors for mental health.
Objectives: Studies of neurocognitively elite older adults, termed SuperAgers, have identified clinical predictors and neurobiological indicators of resilience against age-related neurocognitive decline. Despite rising rates of older persons living with HIV (PLWH), SuperAging (SA) in PLWH remains undefined. We aimed to establish neuropsychological criteria for SA in PLWH and examined clinically relevant correlates of SA. Methods: 734 PLWH and 123 HIV-uninfected participants between 50 and 64 years of age underwent neuropsychological and neuromedical evaluations. SA was defined as demographically corrected (i.e., sex, race/ethnicity, education) global neurocognitive performance within normal range for 25-year-olds. Remaining participants were labeled cognitively normal (CN) or impaired (CI) based on actual age. Chi-square and analysis of variance tests examined HIV group differences on neurocognitive status and demographics. Within PLWH, neurocognitive status differences were tested on HIV disease characteristics, medical comorbidities, and everyday functioning. Multinomial logistic regression explored independent predictors of neurocognitive status. Results: Neurocognitive status rates and demographic characteristics differed between PLWH (SA=17%; CN=38%; CI=45%) and HIV-uninfected participants (SA=35%; CN=55%; CI=11%). In PLWH, neurocognitive groups were comparable on demographic and HIV disease characteristics. Younger age, higher verbal IQ, absence of diabetes, fewer depressive symptoms, and lifetime cannabis use disorder increased likelihood of SA. SA reported increased independence in everyday functioning, employment, and health-related quality of life than non-SA. Conclusions: Despite combined neurological risk of aging and HIV, youthful neurocognitive performance is possible for older PLWH. SA relates to improved real-world functioning and may be better explained by cognitive reserve and maintenance of cardiometabolic and mental health than HIV disease severity. Future research investigating biomarker and lifestyle (e.g., physical activity) correlates of SA may help identify modifiable neuroprotective factors against HIV-related neurobiological aging. (JINS, 2019, 25, 507–519)
Infants with prenatally diagnosed CHD are at high risk for adverse outcomes owing to multiple physiologic and psychosocial factors. Lack of immediate physical postnatal contact because of rapid initiation of medical therapy impairs maternal–infant bonding. On the basis of expected physiology, maternal–infant bonding may be safe for select cardiac diagnoses.
This is a single-centre study to assess safety of maternal–infant bonding in prenatal CHD.
In total, 157 fetuses with prenatally diagnosed CHD were reviewed. On the basis of cardiac diagnosis, 91 fetuses (58%) were prenatally approved for bonding and successfully bonded, 38 fetuses (24%) were prenatally approved but deemed not suitable for bonding at delivery, and 28 (18%) were not prenatally approved to bond. There were no complications attributable to bonding. Those who successfully bonded were larger in weight (3.26 versus 2.6 kg, p<0.001) and at later gestation (39 versus 38 weeks, p<0.001). Those unsuccessful at bonding were more likely to have been delivered via Caesarean section (74 versus 49%, p=0.011) and have additional non-cardiac diagnoses (53 versus 29%, p=0.014). There was no significant difference regarding the need for cardiac intervention before hospital discharge. Infants who bonded had shorter hospital (7 versus 26 days, p=0.02) and ICU lengths of stay (5 versus 23 days, p=0.002) and higher survival (98 versus 76%, p<0.001).
Fetal echocardiography combined with a structured bonding programme can permit mothers and infants with select types of CHD to successfully bond before ICU admission and intervention.
Background: When measuring young Duchenne Muscular Dystrophy (DMD) patients’ health-related quality of life (HRQoL), parent-proxy reports are heavily relied on. Therefore, it is imperative that the relationship between parent-proxy and child self-report HRQoL is understood. This study examined the level of agreement between children and their parent-proxy rating of the child’s HRQoL. Methods: We used FOR-DMD clinical trial baseline data. HRQoL, measured using the PedsQL inventory, was reported by 178 parent and child (ages 4 to 7 years) dyads. Intracorrelation coefficients (ICC) measured absolute agreement while paired t-tests determined differences in the average HRQoL ratings between groups. Results: The level of agreement between child and parent-proxy ratings of HRQoL was poor for the generic PedsQL scale (ICC: 0.29) and its subscales; and, similarly low for the neuromuscular disease module (ICC:0.16). On average, parents rated their child’s HRQoL as poorer than the children rated themselves in all scales except for psychosocial and school functioning. Conclusions: Child and parent-proxy HRQoL ratings are discordant in this study sample, as occurs in other chronic pediatric diseases. This should be taken into account when interpreting clinical and research HRQoL findings in this population. Future studies should examine reasons for parents’ perception of poorer HRQoL than that reported by their children.
Background: Duchenne muscular dystrophy (DMD) is an X-linked disorder affecting 1:3500-5000 live male births, causing a life-limiting form of muscular dystrophy. Whole exon deletions disrupting the reading frame result in near-absence of sarcolemmal dystrophin, essential for muscle function. Eteplirsen is a phosphorodiamidate morpholino oligomer (PMO) designed to induce production of internally-truncated dystrophin in certain patients. Methods: As of June 2016, 150 patients (4-19 years of age) with DMD received eteplirsen in 7 clinical trials. 143 patients received ≥1 intravenous infusion of eteplirsen (range: 0.5 - 50 mg/kg). 81 (54%) received treatment for ≥1 year (Range: 1-4+ years). Results: Common (>15%) adverse events (AEs) were cough, headache, vomiting, back pain, extremity pain, contusion, nasopharyngitis, upper respiratory tract infection, nasal congestion, arthralgia and rash. Non-serious facial flushing, erythema and mild transient temperature elevation occurred with eteplirsen. 10 (6.7%) patients experienced severe AEs; 12 (8%) patients experienced serious AEs. All serious and all but 1 severe AEs were considered unrelated to eteplirsen by the treating physicians. Serial echocardiograms in 12 treated patients demonstrated no functional decline over 4+ years. Conclusions: Eteplirsen’s tolerability will continue to be assessed in ongoing clinical trials.
Background: Spinal Muscular Atrophy (SMA) is an autosomal recessive neurodegenerative disease. In June 2017, Health Canada approved Nusinersen, currently the only available drug for SMA. Since 2016, patients in Ontario have been treated clinically with Nusinersen through different access programs. Methods: Retrospective case series of patients with SMA treated clinically with Nusinersen in Ontario, describing clinical characteristics and logistics of intrathecal Nusinersen administration. Results: Twenty patients have been treated across four centres. To date, we have reviewed 8 cases at one centre (seven SMA Type I, one SMA Type II). Age at first dose ranged from 3-156 months and disease duration 9-166 months. Patients had received 4-7 doses at last evaluation. Three patients with scoliosis (2 with spinal rods) required fluoroscopy-guided radiologist administration, and 4 required general anesthesia. No complications/adverse events were reported. At last follow up, 5/8 families reported improved daily activities. Of 5 patients with baseline and follow up motor function testing, 3 demonstrated improved scores. One patient died due to respiratory decline at age 9 months, despite improved motor outcome scores. Conclusions: We describe the first Canadian post-marketing experience with Nusinersen. Timely dissemination of this information is needed to guide clinicians, hospital administrators, and policy-makers.
Prevalence of skin sores and scabies in remote Australian Aboriginal communities remains unacceptably high, with Group A Streptococcus (GAS) the dominant pathogen. We aim to better understand the drivers of GAS transmission using mathematical models. To estimate the force of infection, we quantified the age of first skin sores and scabies infection by pooling historical data from three studies conducted across five remote Aboriginal communities for children born between 2001 and 2005. We estimated the age of the first infection using the Kaplan–Meier estimator; parametric exponential mixture model; and Cox proportional hazards. For skin sores, the mean age of the first infection was approximately 10 months and the median was 7 months, with some heterogeneity in median observed by the community. For scabies, the mean age of the first infection was approximately 9 months and the median was 8 months, with significant heterogeneity by the community and an enhanced risk for children born between October and December. The young age of the first infection with skin sores and scabies reflects the high disease burden in these communities.
Investigations of drinking behavior across military deployment cycles are scarce, and few prospective studies have examined risk factors for post-deployment alcohol misuse.
Prevalence of alcohol misuse was estimated among 4645 US Army soldiers who participated in a longitudinal survey. Assessment occurred 1–2 months before soldiers deployed to Afghanistan in 2012 (T0), upon their return to the USA (T1), 3 months later (T2), and 9 months later (T3). Weights-adjusted logistic regression was used to evaluate associations of hypothesized risk factors with post-deployment incidence and persistence of heavy drinking (HD) (consuming 5 + alcoholic drinks at least 1–2×/week) and alcohol or substance use disorder (AUD/SUD).
Prevalence of past-month HD at T0, T2, and T3 was 23.3% (s.e. = 0.7%), 26.1% (s.e. = 0.8%), and 22.3% (s.e. = 0.7%); corresponding estimates for any binge drinking (BD) were 52.5% (s.e. = 1.0%), 52.5% (s.e. = 1.0%), and 41.3% (s.e. = 0.9%). Greater personal life stress during deployment (e.g., relationship, family, or financial problems) – but not combat stress – was associated with new onset of HD at T2 [per standard score increase: adjusted odds ratio (AOR) = 1.20, 95% CI 1.06–1.35, p = 0.003]; incidence of AUD/SUD at T2 (AOR = 1.54, 95% CI 1.25–1.89, p < 0.0005); and persistence of AUD/SUD at T2 and T3 (AOR = 1.30, 95% CI 1.08–1.56, p = 0.005). Any BD pre-deployment was associated with post-deployment onset of HD (AOR = 3.21, 95% CI 2.57–4.02, p < 0.0005) and AUD/SUD (AOR = 1.85, 95% CI 1.27–2.70, p = 0.001).
Alcohol misuse is common during the months preceding and following deployment. Timely intervention aimed at alleviating/managing personal stressors or curbing risky drinking might reduce risk of alcohol-related problems post-deployment.
The Molonglo Observatory Synthesis Telescope (MOST) is an 18000 m2 radio telescope located 40 km from Canberra, Australia. Its operating band (820–851 MHz) is partly allocated to telecommunications, making radio astronomy challenging. We describe how the deployment of new digital receivers, Field Programmable Gate Array-based filterbanks, and server-class computers equipped with 43 Graphics Processing Units, has transformed the telescope into a versatile new instrument (UTMOST) for studying the radio sky on millisecond timescales. UTMOST has 10 times the bandwidth and double the field of view compared to the MOST, and voltage record and playback capability has facilitated rapid implementaton of many new observing modes, most of which operate commensally. UTMOST can simultaneously excise interference, make maps, coherently dedisperse pulsars, and perform real-time searches of coherent fan-beams for dispersed single pulses. UTMOST operates as a robotic facility, deciding how to efficiently target pulsars and how long to stay on source via real-time pulsar folding, while searching for single pulse events. Regular timing of over 300 pulsars has yielded seven pulsar glitches and three Fast Radio Bursts during commissioning. UTMOST demonstrates that if sufficient signal processing is applied to voltage streams, innovative science remains possible even in hostile radio frequency environments.
The class of radio transients called Fast Radio Bursts (FRBs) encompasses enigmatic single pulses, each unique in its own way, hindering a consensus for their origin. The key to demystifying FRBs lies in discovering many of them in order to identity commonalities – and in real time, in order to find potential counterparts at other wavelengths. The recently upgraded UTMOST in Australia, is undergoing a backend transformation to rise as a fast transient detection machine. The first interferometric detections of FRBs with UTMOST, place their origin beyond the near-field region of the telescope thus ruling out local sources of interference as a possible origin. We have localised these bursts to much better than the ones discovered at the Parkes radio telescope and have plans to upgrade UTMOST to be capable of much better localisation still.
Free-range laying hen systems are increasing within Australia. The pullets for these systems are typically reared indoors before being provided first range access around 21 to 26 weeks of age. Thus, the rearing and laying environments are disparate and hens may not adapt well to free-range housing. In this study, we reared 290 Hy-Line® Brown day-old chicks divided into two rooms each with feed, water and litter. In the enriched room, multiple structural, manipulable, visual and auditory stimuli were also provided from 4 to 21 days, the non-enriched room had no additional objects or stimuli. Pullets were transferred to the laying facility at 12 weeks of age and divided into six pens (three enriched-reared, three non-enriched-reared) with identical indoor resources and outdoor range area. All birds were first provided range access at 21 weeks of age. Video observations of natural disturbance behaviours on the range at 22 to 23 and 33 to 34 weeks of age showed no differences in frequency of disturbance occurrences between treatment groups (P=0.09) but a decrease in disturbance occurrences over time (P<0.0001). Radio-frequency identification tracking of individually tagged birds from 21 to 37 weeks of age showed enriched birds on average, spent less time on the range each day (P<0.04) but with a higher number of range visits than non-enriched birds from 21 to 24 weeks of age (P=0.01). Enriched birds accessed the range on more days (P=0.03) but over time, most birds in both treatment groups accessed the range daily. Basic external health scoring showed minimal differences between treatment groups with most birds in visibly good condition. At 38 weeks of age all birds were locked inside for 2 days and from 40 to 42 weeks of age the outdoor range was reduced to 20% of its original size to simulate stressful events. The eggs from non-enriched birds had higher corticosterone concentrations following lock-in and 2 weeks following range reduction compared with the concentrations within eggs from enriched birds (P<0.0001). Correspondingly, the enriched hens showing a greater increase in the number of visits following range area reduction compared to non-enriched hens (P=0.02). Only one rearing room per treatment was used but these preliminary data indicate 3 weeks of early enrichment had some long-term effects on hen ranging behaviour and enhanced hen’s adaptability to environmental stressors.
The stress sensitization theory hypothesizes that individuals exposed to childhood adversity will be more vulnerable to mental disorders from proximal stressors. We aimed to test this theory with respect to risk of 30-day major depressive episode (MDE) and generalized anxiety disorder (GAD) among new US Army soldiers.
The sample consisted of 30 436 new soldier recruits in the Army Study to Assess Risk and Resilience (Army STARRS). Generalized linear models were constructed, and additive interactions between childhood maltreatment profiles and level of 12-month stressful experiences on the risk of 30-day MDE and GAD were analyzed.
Stress sensitization was observed in models of past 30-day MDE (χ28 = 17.6, p = 0.025) and GAD (χ28 = 26.8, p = 0.001). This sensitization only occurred at high (3+) levels of reported 12-month stressful experiences. In pairwise comparisons for the risk of 30-day MDE, the risk difference between 3+ stressful experiences and no stressful experiences was significantly greater for all maltreatment profiles relative to No Maltreatment. Similar results were found with the risk for 30-day GAD with the exception of the risk difference for Episodic Emotional and Sexual Abuse, which did not differ statistically from No Maltreatment.
New soldiers are at an increased risk of 30-day MDE or GAD following recent stressful experiences if they were exposed to childhood maltreatment. Particularly in the military with an abundance of unique stressors, attempts to identify this population and improve stress management may be useful in the effort to reduce the risk of mental disorders.
Migrants are considered a key group at risk for HIV infection. This study describes differences between migrants and the Spanish-born population as they progress through the HIV care cascade in Catalonia, Spain. This study found that among people reached by prevention activities, migrants had a higher number of barriers to access HIV testing services than Spanish-born people, driven primarily by shared risk factors. Between 2001 and 2013, 9829 new HIV diagnoses were reported in Catalonia, the proportion of migrants increasing from 24% in 2001 to 41% in 2013. Compared with Spanish-born people, migrants had a higher proportion of women at diagnosis (24·6% vs. 16·7%), and were younger (median age of 33 vs. 37). The most frequent at-risk population was MSM (men who have sex with men) in both migrants and Spanish-born people, (40% and 43%, respectively), although there were significant differences by region of origin. People from sub-Saharan Africa had the highest proportion of late diagnosis (63·7%). Compared with the Spanish-born population, migrants on follow-up had a lower proportion of people on antiretroviral therapy (ART) (93·7% vs. 90·8%, P < 0·001) and with viral suppression (87·2% vs. 82·9%, P < 0·001). Migrants have higher number of barriers to access HIV testing services, lower retention rates and proportions on ART as compared with Spanish-born people, these differences not being uniform between migrants from different regions.
Free-range laying hen systems are increasing within Australia and research is needed to determine optimal outdoor stocking densities. Six small (n=150 hens) experimental flocks of ISA Brown laying hens were housed with access to ranges simulating one of three outdoor stocking densities with two pen replicates per density: 2000 hens/ha, 10 000 hens/ha or 20 000 hens/ha. Birds were provided daily range access from 21 to 36 weeks of age and the range usage of 50% of hens was tracked using radio-frequency identification technology. Throughout the study, basic external health assessments following a modified version of the Welfare Quality® protocol showed most birds were in visibly good condition (although keel damage was increasingly present with age) with few differences between stocking densities. Toenail length at 36 weeks of age was negatively correlated with hours spent ranging for all pens of birds (all r⩾−0.23, P⩽0.04). At 23 weeks of age, there were no differences between outdoor stocking densities in albumen corticosterone concentrations (P=0.44). At 35 weeks of age, density effects were significant (P<0.001) where the eggs from hens in the highest outdoor stocking density showed the highest albumen corticosterone concentrations, although eggs from hens in the 10 000 hens/ha density showed the lowest concentrations (P<0.017). Behavioural observations of hens both on the range and indoors showed more dust bathing and foraging (scratching followed by ground-pecking) was performed outdoors, but more resting indoors (all P<0.001). Hens from the 2000 hens/ha densities showed the least foraging on the range but the most resting outdoors, with hens from the 20 000 hens/ha densities showing the least amount of resting outdoors (all P<0.017). Proportions of dust bathing outdoors tended to differ between the stocking densities (P=0.08). For each of the health and behavioural measures there were differences between pen replicates within stocking densities. These data show outdoor stocking density has some effects on hen welfare, and it appears that consideration of both individual and group-level behaviour is necessary when developing optimal stocking density guidelines and free-range system management practices.
The present study investigated alteration of brain resting-state activity induced by antidepressant treatment and attempted to investigate whether treatment efficacy can be predicted at an early stage of pharmacological treatment.
Forty-eight first-episode medication-free patients diagnosed with major depression received treatment with escitalopram. Resting-state functional magnetic resonance imaging was administered prior to treatment, 5 h after the first dose, during the course of pharmacological treatment (week 4) and at endpoint (week 8). Resting-state activity was evaluated in the course of the 8-week treatment and in relation to clinical improvement.
Escitalopram dynamically modified resting-state activity in depression during the treatment. After 5 h the antidepressant induced a significant decrease in the signal in the occipital cortex and an increase in the dorsolateral and dorsomedial prefrontal cortices and middle cingulate cortex. Furthermore, while remitters demonstrated more obvious changes following treatment, these were more modest in non-responders suggesting possible tonic and dynamic differences in the serotonergic system. Changes after 5 h in the caudate, occipital and temporal cortices were the best predictor of clinical remission at endpoint.
This study revealed the possibility of using the measurement of resting-state neural changes a few hours after acute administration of antidepressant to identify individuals likely to remit after a few weeks of treatment.