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Mixed presentations, defined by simultaneous occurrence of depressive and manic symptoms, are difficult to treat. Antidepressants, although commonly used, have weak evidence of efficacy and may increase risk of mood destabilization. The aim of this pooled post hoc analysis was to evaluate the efficacy of cariprazine in the treatment of bipolar depression with or without concurrent manic symptoms.
Patients from 3 randomized, double-blind, placebo-controlled studies who met DSM-IV-TR or DSM-5 criteria for bipolar I disorder with a current major depressive episode were identified to have concurrent manic symptoms by baseline Young Mania Rating Scale total score ≥4. Efficacy was assessed in cariprazine 1.5 and 3 mg/day dose groups versus placebo; analyses included the least squares mean change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score.
Of 1383 patients randomized to treatment, 808 (58.4%) had concurrent manic symptoms. For patients with manic symptoms, mean reduction in MADRS total score from baseline to week 6 was significantly greater for both cariprazine 1.5 and 3 mg/day compared with placebo, with least squares mean differences (LSMDs) versus placebo of −2.5 (p = .0033) and −2.9 (p = .0010), respectively; for patients without manic symptoms, the LSMD was significant for 1.5 mg/day (−3.3; p = .0008), but not for 3 mg/day (−1.9; p = .0562).
The results of this post hoc analysis suggest that cariprazine may be an appropriate treatment option for patients with bipolar I depression with or without manic symptoms, with higher doses potentially more effective in patients with manic symptoms.
The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
Hepatic encephalopathy (HE) is a complex neuropsychiatric disorder, manifestations of which range from subtle abnormalities demonstrable only on neuropsychometric testing, such as mild cognitive impairment, psychomotor slowing, and impaired bimanual and visuomotor coordination (referred to as minimal HE or MHE), through to overt manifestations such as disruption of the sleep cycle, disturbed attention span, change in personality, confusion, disorientation, and coma. Aside from the uncommon patient with HE due to a congenital deficiency of an urea cycle enzyme, in whom liver function is otherwise normal, HE occurs as a consequence of severe acute or chronic liver disease or in the setting of porto-systemic venous shunting, the latter arising either spontaneously, usually in the presence of portal venous hypertension complicating cirrhosis, or iatrogenically, following portal venous hypertension-decompressive shunt procedures, both surgical and radiologically placed. Irrespective of the clinical setting in which it arises, the severity of overt HE is traditionally graded using systems such as the West Haven criteria  (Table 30.1).
OBJECTIVES/SPECIFIC AIMS: The objective of this study is to assess the efficacy of combined AF and NP repairs to prevent degenerative changes and restore native disc morphology in an in vivo large animal model. We hypothesize that combined repairs will prevent disc degeneration following injury to a greater extent than the individual repairs after 6 weeks in vivo, as demonstrated through disc height measurements and disc morphology. METHODS/STUDY POPULATION: A total of 8 skeletally mature female Finn sheep were used in this study. Following a previously described method, IVDs from L1 to L6 of the lumbar spine were exposed using a lateral access, extraperitoneal approach5. IVDs were randomized into 5 treatment groups: 1) intact discs, 2) discs injured via a 3 cm x 1 cm box annulotomy and partial nucleotomy, 3) injury followed by a high density collagen (HDC) AF patch, 4) injury followed by injection of a modified hyaluronic acid (HA) into the NP, and 5) injury followed by both the HDC AF patch and HA NP injection. The HDC treatment was 15 mg/mL type-I collagen mixed with 0.06mM riboflavin, injected at the defect site and crosslinked in situ with blue light. The NP injection was HA modified with C16 side chains to increase the viscosity of the hydrogel (HYADD 4®)6. At 6 weeks post-operatively, sheep were sacrificed and had 3T magnetic resonance images (MRI) taken of their lumbar spine. Disc height analysis and Pfirrmann grading were performed on each segment using MR images. Additionally, quantitative MRI analyses were performed using a custom MATLAB algorithm that segments NP from the surrounding tissue and directly measures the NP volume. ANOVA with Tukey’s HSD was used to determine statistical significance between groups for disc height and quantitative MRI analyses, and the Kruskal-Wallis test with Mann-Whitney tests was used to statistically analyze Pfirrmann Grades. All animal use followed approved IACUC protocol. RESULTS/ANTICIPATED RESULTS: As shown in axial MR images (Figure 1A), intact discs had hyperintense NP with a distinct border to the AF. The discs receiving injury with no treatment had hypointense NP with no distinct border between the AF and NP. Individual and combined treatment with the HA NP injection and HDC AF patch appeared to preserve the hyperintense NP signal and AF/NP border. Intact control discs were not degenerated and had an average Pfirrmann grade of 1 (Figure 1B), while injured, untreated discs had significant degeneration with an average Pfirrmann grade of 3. Discs receiving the HA NP injection and collagen AF patch individually showed fewer signs of degeneration than the injured alone, and the combined treatment resulted in the least amount of degeneration with Pfirrmann grades not significantly different than the intact controls. Disc height index confirmed the trends seen in the Pfirrmann grades (Figure 1C), where injured discs lost 20% of the intact disc height, the individual NP and AF repairs restored 5-10% of intact disc height, and the combined repairs preserved 90% of the intact disc height. The NP voxel count of all treatment groups were similar to the intact controls (Figure 1D). DISCUSSION/SIGNIFICANCE OF IMPACT: The objective of this study was to determine how combined AF and NP can prevent degenerative changes to the disc in a large animal in vivo model. Pfirrmann grading and disc height index results show that the greatest preservation of disc morphology was seen with combined AF and NP repairs, while the individual strategies prevented degenerative changes better than injury with no treatment. It appears the HA NP injection restores lost water content to the disc following injury, and the AF collagen patch plays a role in maintaining the NP repair within the disc. This is the first study to our knowledge to attempt combined AF and NP repairs in an in vivo large animal model. Combining NP and AF repairs leads to significantly improved outcomes following disc injury, which warrants the translation of combined repairs into the clinic to improve patient outcomes with degenerative disc disease involving NP and AF.
During the past two decades, it has been amply documented that neuropsychiatric disorders (NPDs) disproportionately account for burden of illness attributable to chronic non-communicable medical disorders globally. It is also likely that human capital costs attributable to NPDs will disproportionately increase as a consequence of population aging and beneficial risk factor modification of other common and chronic medical disorders (e.g., cardiovascular disease). Notwithstanding the availability of multiple modalities of antidepressant treatment, relatively few studies in psychiatry have primarily sought to determine whether improving cognitive function in MDD improves patient reported outcomes (PROs) and/or is cost effective. The mediational relevance of cognition in MDD potentially extrapolates to all NPDs, indicating that screening for, measuring, preventing, and treating cognitive deficits in psychiatry is not only a primary therapeutic target, but also should be conceptualized as a transdiagnostic domain to be considered regardless of patient age and/or differential diagnosis.
Ondansetron is increasingly administered to children suffering from concussion-associated nausea/vomiting. We examined the association between ondansetron administration and post-concussion symptoms in children at 1 week and 1 month following the concussion.
This was a secondary analysis of data collected prospectively in a cohort study conducted in nine pediatric emergency departments (EDs) (5P study). Participants were children ages between 5 and 17.99 years who sustained a concussion in the previous 48 hours. For the current study, only 5P participants who reported nausea and/or vomiting in the ED were eligible. The exposure of interest was ondansetron administration; the comparison group included all other participants. The primary outcome was an increase in at least three symptoms of the Post-Concussion Symptom Inventory score at 1 week and 1 month following trauma.
Among the 3,063 children included in the 5P study, 1805 (59%) reported nausea and provided data at 1 week and/or 1 month. Among them, 132 (7%) received ondansetron. Multivariable logistic regression adjusted for confounders did not show an association between ondansetron use and the risk of persistent post-concussion symptoms at 1 week (OR: 1.13 [95% CI: 0.86-1.49]), but it was associated with a higher risk at 1 month (OR: 1.33 [95% CI: 1.05-1.97]).
In children presenting to the ED with an acute concussion, ondansetron use was associated with a higher risk of persistent post-concussion symptoms at 1 month. Although this may be related to the limitations of the design, it highlights the importance of evaluating this association using a randomized clinical trial.
The classical point of view—that major depressive episodes (MDEs), no matter what additional symptoms are present, should be treated first line with antidepressants—is now giving way to new a notion. The idea is that MDEs mixed with a few symptoms of mania/hypomania should be viewed very differently in terms of their natural history, clinical outcome, and treatment, and perhaps certain antipsychotics should be given as first-line treatment rather than antidepressant monotherapy.
A significant minority of people presenting with a major depressive episode (MDE) experience co-occurring subsyndromal hypo/manic symptoms. As this presentation may have important prognostic and treatment implications, the DSM–5 codified a new nosological entity, the “mixed features specifier,” referring to individuals meeting threshold criteria for an MDE and subthreshold symptoms of (hypo)mania or to individuals with syndromal mania and subthreshold depressive symptoms. The mixed features specifier adds to a growing list of monikers that have been put forward to describe phenotypes characterized by the admixture of depressive and hypomanic symptoms (e.g., mixed depression, depression with mixed features, or depressive mixed states [DMX]). Current treatment guidelines, regulatory approvals, as well the current evidentiary base provide insufficient decision support to practitioners who provide care to individuals presenting with an MDE with mixed features. In addition, all existing psychotropic agents evaluated in mixed patients have largely been confined to patient populations meeting the DSM–IV definition of “mixed states” wherein the co-occurrence of threshold-level mania and threshold-level MDE was required. Toward the aim of assisting clinicians providing care to adults with MDE and mixed features, we have assembled a panel of experts on mood disorders to develop these guidelines on the recognition and treatment of mixed depression, based on the few studies that have focused specifically on DMX as well as decades of cumulated clinical experience.
To describe why and how capacity-building systems for scaling up nutrition programmes should be constructed in low- and middle-income countries (LMIC).
Position paper with task force recommendations based on literature review and joint experience of global nutrition programmes, public health nutrition (PHN) workforce size, organization, and pre-service and in-service training.
The review is global but the recommendations are made for LMIC scaling up multisectoral nutrition programmes.
The multitude of PHN workers, be they in the health, agriculture, education, social welfare, or water and sanitation sector, as well as the community workers who ensure outreach and coverage of nutrition-specific and -sensitive interventions.
Overnutrition and undernutrition problems affect at least half of the global population, especially those in LMIC. Programme guidance exists for undernutrition and overnutrition, and priority for scaling up multisectoral programmes for tackling undernutrition in LMIC is growing. Guidance on how to organize and scale up such programmes is scarce however, and estimates of existing PHN workforce numbers – although poor – suggest they are also inadequate. Pre-service nutrition training for a PHN workforce is mostly clinical and/or food science oriented and in-service nutrition training is largely restricted to infant and young child nutrition.
Unless increased priority and funding is given to building capacity for scaling up nutrition programmes in LMIC, maternal and child undernutrition rates are likely to remain high and nutrition-related non-communicable diseases to escalate. A hybrid distance learning model for PHN workforce managers’ in-service training is urgently needed in LMIC.
Metribuzin has a 60-d preharvest interval (PHI) in potato, which limits utility of metribuzin POST in potato. In certain years, the potato may not fully cover the area between the potato rows. This allows for late-season weed emergence and subsequent yield reduction through direct competition or harvest interference. Field experiments were conducted in 2011 at Castle Hayne, NC; Freeville, NY; Hasting, FL; and Plymouth, NC to determine the effect of a 30-d PHI on potato crop tolerance. The cultivars planted were ‘Superior' and ‘Yukon Gold' in Castle Hayne and Plymouth, ‘Castille' and Yukon Gold in Freeville, and ‘Atlantic' in Hastings. Treatments included metribuzin at 278 g ai ha−1 PRE, 30, and 60 d before harvest (DBH), and metribuzin at 556 g ha−1 at 30 and 60 DBH. Split application treatments included metribuzin at 556 g ha−1 at PRE followed by metribuzin at 556 g ha−1 30 or 60 DBH and metribuzin at 842 g ha−1 PRE followed by metribuzin at 278 g ha−1 at 30 or 60 DBH. Potato injury was ≤ 8% at all locations, and injury was transient. There were no differences observed between metribuzin rate or application date for individual potato grades or total yield. Reducing the PHI in potato to 30 d would have no effect on yield and would provide a longer period for controlling broadleaf weeds.
The conservation of biodiversity is an increasingly challenging endeavour. Current pressures from a growing human population have led to concerns of a sixth mass extinction event, bringing mounting pressure to find effective ways of conserving biodiversity (Barnosky et al., 2011). However, our ability to meet this challenge is affected by the fact that not everyone supports conservation objectives. People naturally have different interests and priorities, some of which may be diametrically opposed to conservation objectives. In some cases, these differences lead to damaging and costly conflicts that we see emerging across the world and which present major challenges to modern conservation (MacDonald and Service, 2007).
At a cursory glance, the conflicts that surface around conservation often appear to be about impact: the impact of carnivores on livestock; the impact of wind farms on birds; or the impact of protected areas on livelihoods. Consequently, a common approach to these problems has been to build robust science and develop an evidence base to understand these impacts and find ways of reducing them, often through technical solutions. This approach, however, rarely works for the simple reason that many of these conflicts are about much more than impact. So even if we can develop the science to quantify impacts and show how they can be reduced, the conflicts can stubbornly persist. Indeed, beneath the surface of any of the conflicts discussed in this book is a complex layering of diverse issues related to different world views, issues of trust, power imbalances or latent historical issues – issues that lie well outside the sphere of the natural sciences. So, if we really want to understand and tackle these thorny problems, we need insights from other disciplines as well as from the practitioners specialising in resolving conflicts.
The growing recognition of the complexity within conflicts has led many authors to suggest more cross-disciplinary approaches, especially through better integration of ecological and social science (Manfredo and Dayer, 2004; Sillero-Zubiri et al., 2007; Treves, 2009; Dickman, 2010; White and Ward, 2010).
We present the results of an approximately 6 100 deg2 104–196 MHz radio sky survey performed with the Murchison Widefield Array during instrument commissioning between 2012 September and 2012 December: the MWACS. The data were taken as meridian drift scans with two different 32-antenna sub-arrays that were available during the commissioning period. The survey covers approximately 20.5 h < RA < 8.5 h, − 58° < Dec < −14°over three frequency bands centred on 119, 150 and 180 MHz, with image resolutions of 6–3 arcmin. The catalogue has 3 arcmin angular resolution and a typical noise level of 40 mJy beam− 1, with reduced sensitivity near the field boundaries and bright sources. We describe the data reduction strategy, based upon mosaicked snapshots, flux density calibration, and source-finding method. We present a catalogue of flux density and spectral index measurements for 14 110 sources, extracted from the mosaic, 1 247 of which are sub-components of complexes of sources.