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Mortality of animals on roads is a critical threat to many wildlife populations and is poised to increase strongly because of ongoing and planned road construction. If these new roads cannot be avoided, effective mitigation measures will be necessary to stop biodiversity decline. Fencing along roads effectively reduces roadkill and is often used in combination with wildlife passages. Because fencing the entire road is not always possible due to financial constraints, high-frequency roadkill areas are often identified to inform the placement of fencing. We devised an adaptive fence-implementation plan to prioritize road sections for fencing. In this framework, areas along roads of high, moderate, and low levels of animal mortality (respectively, roadkill hotspots, warmspots, and coldspots) are identified at multiple scales (i.e., in circles of different diameters [200-2000 m] in which mortality frequency is measured). Fence deployment is based on the relationship between the amount of fencing being added to the road, starting with the strongest roadkill hotspots, and potential reduction in road mortality (displayed in mortality-reduction graphs). We applied our approach to empirical and simulated spatial patterns of wildlife-vehicle collisions. The scale used for analysis affected the number and spatial extent of roadkill hot-, warm-, and coldspots. At fine scales (e.g., 200 m), more hotspots were identified than at coarse scales (e.g., 2000 m), but combined the fine-scale hotspots covered less road and less fencing was needed to reduce road mortality. However, many short fences may be less effective in practice due to a fence-end effect (i.e., animals moving around the fence more easily), resulting in a trade-off between few long and many short fences, which we call the FLOMS (few-long-or-many-short) fences trade-off. Thresholds in the mortality-reduction graphs occurred for some roadkill patterns, but not for others. Thresholds may be useful to consider when determining road-mitigation targets. The existence of thresholds at multiple scales and the FLOMS trade-off have important implications for biodiversity conservation.Un Plan Adaptativo para la Priorización de Secciones de Carretera para Cercar y Reducir la Mortalidad Animal Resumen La mortalidad de los animales en las carreteras es una amenaza muy importante para las poblaciones silvestres y se pronostica que aumentarán enérgicamente debido a la construcción continua y planeada de carreteras. Si estas nuevas carreteras no pueden evitarse, se necesitarán medidas efectivas de mitigación para detener la declinación de la biodiversidad. El cercado a lo largo de las carreteras reduce efectivamente los atropellamientos y se usa frecuentemente junto con los pasos de fauna. Ya que cercar por completo la carretera no siempre es posible debido a las restricciones financieras, es común identificar las áreas con una frecuencia alta de atropellamientos para que la colocación de cercas esté informada al respecto. Diseñamos un plan adaptativo de implementación de cercas para priorizar las secciones de carretera que requieren ser cercadas. En este marco de trabajo, identificamos las áreas a lo largo de las carreteras con un nivel alto, moderado y bajo de mortalidad animal (respectivamente, puntos calientes, cálidos y fríos de atropellamiento) a diferentes escalas (es decir, en círculos de diferentes diámetros [200-2000 m] dentro de los cuales se mide la frecuencia de la mortalidad). El despliegue de cercas está basado en la relación entre la cantidad de cercas que se van añadiendo a la carretera, iniciando en los puntos calientes de atropellamiento, y la reducción potencial de la mortalidad en la carretera (presentada en gráficas de reducción de la mortalidad). Aplicamos nuestra estrategia a los patrones espaciales empíricos y simulados de las colisiones entre vehículos y animales. La escala utilizada para el análisis afectó al número y a la extensión espacial de los puntos calientes, cálidos y fríos de los atropellamientos. A escalas finas (p. ej.: 200 m), se identificaron más puntos calientes que a escalas más amplias (p. ej.: 2000 m), pero combinadas las escalas finas, los puntos calientes cubrieron una superficie menor de la carretera y se necesitaron menos cercas para reducir la mortalidad. Sin embargo, muchas cercas cortas pueden ser menos efectivas en la práctica debido al efecto de fin de valla (es decir, que los animales se muevan alrededor de la cerca con mayor facilidad), lo que resulta en una compensación entre pocas cercas largas y muchas cercas cortas, que denominamos compensación de cercas FLOMS (pocas-largas-o-muchas-cortas). Los umbrales en las gráficas de reducción de la mortalidad se presentaron para algunos patrones de atropellamiento, pero no para otros. Los umbrales pueden ser útiles para considerar cuando se determinan los objetivos de mitigación para las carreteras. La existencia de los umbrales a escalas múltiples y la compensación de FLOMS tienen implicaciones importantes para la conservación de la biodiversidad.动物被路杀是许多野生动物种群面临的一项严重威胁。考虑到正在进行和计划实施的道路建设, 这一问题还将日益加剧。如果无法避免建设新道路, 就必须采取有效的缓解措施来阻止生物多样性下降。在道路两旁修建围栏可以有效减少路杀, 且经常与野生动物通道结合使用。由于资金限制, 通常不能沿整条道路设置围栏, 因此一般会找出路杀高发地段来为围栏的布设提供信息。我们设计了一个适应性的围栏建设实施计划, 来确定优先建设围栏的路段。在这个框架中, 我们在多尺度上 (即在 200-2000 米直径的圆内测量路杀死亡率) 确定了路杀频率高、中、低的道路沿线地区 (分别是路杀热点地区、暖点地区和冷点地区) 。围栏布设是基于道路上从路杀热点地区开始的增加围栏的数量, 与可能的路杀死亡率降低 (通过死亡率下降图来显示) 之间的关系。我们将该方法应用于野生动物-车辆撞击的经验和模拟空间模型中, 发现用于分析的尺度影响了路杀热点、暖点、冷点地区的数量和空间范围。在精细尺度下 (如 200 米) 比在粗糙尺度下 (如 2000 米) 能识别出更多热点地区, 但将精细尺度下的热点地区结合起来只覆盖了较少的道路, 为减少路杀而需要建设的围栏也较少。然而, 由于存在围栏末端效应 (即动物可以更轻易地绕过围栏) , 建设许多短围栏在实践中可能不够有效, 因此需要在少量长围栏和大量短围栏之间进行取舍, 我们称之为 FLOMS (few-long-or-many-short, 少量长围栏或大量短围栏) 的权衡。此外, 某些路杀模式的死亡率下降图中出现了阈值, 而其它模式则没有。在确定减缓路杀影响的目标时, 阈值可能有一定帮助。多尺度下的阈值存在和 FLOMS 权衡对生物多样性保护具有重要意义。【翻译: 胡怡思; 审校: 聂永刚】.

Objective: There is a dearth of research about the aging process among individuals with bipolar disorder (BD). One potential strategy to overcome the challenge of interpreting findings from existing limited older-age bipolar disorder (OABD) research studies is to pool or integrate data, taking advantage of potential overlap or similarities in assessment methods and harmonizing or cross-walking measurements where different measurement tools are used to evaluate overlapping construct domains. This report describes the methods and initial start-up activities of a first-ever initiative to create an integrated OABD-focused database, the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) project. Methods: Building on preliminary work conducted by members of the International Society for Bipolar Disorders OABD taskforce, the GAGE-BD project will be operationalized in four stages intended to ready the dataset for hypothesis-driven analyses, establish a consortium of investigators to guide exploration, and set the stage for prospective investigation using a common dataset that will facilitate a high degree of generalizability. Results: Initial efforts in GAGE-BD have brought together 14 international investigators representing a broad geographic distribution and data on over 1,000 OABD. Start-up efforts include communication and guidance on meeting regulatory requirements, establishing a Steering Committee to guide an incremental analysis strategy, and learning from existing multisite data collaborations and other support resources. Discussion: The GAGE-BD project aims to advance understanding of associations between age, BD symptoms, medical burden, cognition and functioning across the life span and set the stage for future prospective research that can advance the understanding of OABD.

Objective Older patients with bipolar disorder (BD) present with variable degrees of cognitive impairment. Over time, stress, mood episodes, and comorbidities increase the body's allostatic load. We assessed the extent to which allostatic load vs more traditional measures of medical burden account for the heterogeneity in cognition in this population. Methods Thirty-five older euthymic patients with BD and 30 age-equated, gender-equated, and education-equated comparison participants were administered a comprehensive assessment including a neuropsychological battery, and 9 physiological measures to determine allostatic load. The relationship among allostatic load, medical burden, and cognition was assessed. Results Compared with the mentally healthy comparators, patients were impaired globally, and in 4 cognitive domains-information-processing speed / executive functioning, delayed memory, language, and visuomotor ability, and presented with greater medical burden but not a different allostatic load. Allostatic load, but not medical burden, was associated with delayed memory performance both in a correlational analysis and in a multivariate regression analysis. Conclusion Euthymic older patients with BD are impaired on several cognitive domains and have high medical burden. Their memory performance is more strongly associated with allostatic load than with traditional measures of medical burden. These findings need to be replicated and extended longitudinally.

Objective Older adults with bipolar disorder (OABD) are a growing segment of patients with bipolar disorder (BD) for which specific guidelines are warranted. Although, OABD are frequently excluded from randomized controlled trials due to their age or somatic comorbidity, more treatment data from a variety of sources have become available in recent years. It is expected that at least some of this emerging information on OABD would be incorporated into treatment guidelines available to clinicians around the world. Methods The International Society of Bipolar Disorders OABD task force compiled and compared recommendations from current national and international guidelines that specifically address geriatric or older individuals with BD (from year 2005 onwards). Results There were 34 guidelines, representing six continents and 19 countries. The majority of guidelines had no separate section on OABD. General principles for treating OABD with medication are recommended to be similar to those for younger adults, with special caution for side effects due to somatic comorbidity and concomitant medications. Therapeutic lithium serum levels are suggested to be lower but recommendations are very general and mostly not informed by specific research evidence. Conclusions There is a lack of emphasis of OABD-specific issues in existing guidelines. Given the substantial clinical heterogeneity in BD across the life span, along with the rapidly expanding population of older individuals worldwide, and limited mental health workforce with geriatric expertise, it is critical that additional effort and resources be devoted to studying treatment interventions specific to OABD and that treatment guidelines reflect research findings. Copyright © 2016 John Wiley & Sons, Ltd.

OBJECTIVE Using the database of the NIMH-sponsored Acute Treatment of Late Life Mania study (GERI-BD), we assessed the role of social support in the presentation of late-life bipolar mania.

Objective Cognitive impairments are a feature of bipolar disorder (BD) and could be worsened by inflammatory cytokines. We determined whether (i) serum interleukin-1 receptor antagonist (IL-1RA) was increased in elderly BD subjects; (ii) whether IL-1RA was associated with worse neurocognitive function; and (iii) whether IL-1RA was associated with white matter integrity. Methods Twenty-one euthymic BD patients (65 +/− 9 years) with serum available for IL-1RA measures by enzyme-linked immunoassays were compared with 26 similarly aged control participants. Four factor analysis-derived z-scores and a global z-score were obtained from a battery of 21 neurocognitive tests. Diffusion tensor images were used to obtain fractional anisotropy (FA), and an automated labeling pathway algorithm was used to obtain white matter hyperintensity burden. Results Interleukin-1 receptor antagonist was elevated in BD subjects compared with controls (439+/−326 pg/mL vs. 269+/−109 pg/mL; p = 0.004). Moreover, IL-1RA was inversely correlated with three cognitive function factors and global cognition (r = −0.37; p = 0.01). IL-1RA continued to correlate with global cognitive function even when covarying for either IL-6 or brain-derived neurotrophic factor. Although FA was lower in BD subjects (0.368 +/− 0.02 vs. 0.381 +/− 0.01; p = 0.02), IL-1RA was not associated with FA or white matter hyperintensity burden. Conclusion Elevated serum levels of IL-1RA in BD subjects, even during euthymic states, were associated with worse cognitive function. This association was not explained by co-occurring increases in IL-6, by decreased brain-derived neurotrophic factor, nor by measures of white matter integrity. These cross-sectional findings support the possibility that the IL-1 family may contribute to cognitive impairments in BD. Copyright © 2013 John Wiley & Sons, Ltd.

Objectives Cognitive dysfunction is prevalent in older adults with bipolar disorder (BD). High white matter hyperintensity (WMH) burden, a marker of white matter disease, detected on T2/fluid-attenuated inversion recovery brain magnetic resonance imaging (MRI) has been consistently reported in BD across all age ranges, including older adults. Yet, whether high WMH burden is related to the excess cognitive impairment present in older adults with BD is unknown. Therefore, we examine whether higher WMH burden is related to worse cognitive function in older adults with BD. Methods This is a cross-sectional study of 27 non-demented BD patients aged ≥50 years and 12 similarly aged mentally healthy comparators (controls). Subjects underwent both brain MRI and comprehensive neurocognitive assessment. We employed correlational analyses to evaluate the burden of WMH and the relationship between WMH and cognitive function. Results Although BD subjects had worse performance in all cognitive domains, BD subjects had less total WMH burden (t[13.4] = −3.57, p = 0.003). In control subjects, higher WMH was related to lower global cognitive function (ρ = −0.57, n = 12, p = 0.05). However, WMH did not correlate with neuropsychological performance in BD subjects. Further, BD and control subjects did not differ with respect to total gray and hippocampal volumes. Conclusions Cognitive dysfunction in late-life BD does not appear to be due primarily to processes related to increased WMH or reduced gray matter volume. Future longitudinal studies should examine other potential neuroprogressive pathways such as inflammation, mitochondrial dysfunction, serum anticholinergic burden, and altered neurogenesis. Copyright © 2013 John Wiley & Sons, Ltd.

The pseudo-octahedral nitrosyl species trans-[Ru(DMAP)4(NO)(OH)]2+ [12+, DMAP = 4-(dimethylamino)pyridine] was prepared by the reaction between [Ru(DMAP)5(H2O)]2+ and NaNO2 under mild conditions (room temperature, pH = 6–8), and precipitated with NaBF4 or NaPF6. Single-crystal X-ray diffraction data of 1(BF4)2·2H2O point to a {RuNO}6 electronic configuration of the cation, although there is a significant deviation from the expected linear arrangement of the RuNO moiety (Ru–N–O angle: 169.3°). The remarkably low wavenumber of the NO stretching band (νNO) of 1832 cm–1 in the solid state corresponds to an electron-rich ligand environment with strong backbonding interactions between dπ metal orbitals and π*NO orbitals of the (formal) NO+ (nitrosonium) ligand. Consistently, the complex acts as a poor electrophile: it is extremely unreactive toward OH– and toward the stronger nucleophile cysteine. Cyclic voltammetry (CV) experiments show three reduction processes in acetonitrile. The first one at –0.50 V [vs. Ag/AgCl, KCl(s)] is reversible on the CV time scale. Spectroelectrochemical experiments (IR and UV/Vis) suggest that the reduced complex has a {RuNO}7 configuration. The νNO wavenumber of 1603 cm–1 agrees with a reduction mostly centered at the nitrosyl ligand. This species appears to be inert toward substitution in the coordination sphere, and the original {RuNO}6 ion can be quantitatively recovered upon oxidation. In contrast, further reduction of this species is completely irreversible, even on the CV timescale, which is probably due to the lability of the presumably formed nitroxyl (NO–) ligand.

In late life, bipolar disorder (BD) and major depressive disorder (MDD) are associated with cognitive dysfunction even when patients are euthymic (1–6). Both disorders are also associated with increased rates of dementia (7, 8). In addition to impaired cognitive function, these disorders may interfere with everyday functional abilities (9). Whether BD and MDD have similar or different cognitive profiles and levels of impairment in older age is not clear. Identifying whether there are relevant differences may help in understanding the neurobiology of these illnesses and developing specific interventions for BD or MDD to prevent, halt, or remediate cognitive impairment and functional decline. For example, deficits in memory may require different treatments than deficits in executive function. Additionally, if both disorders are associated with comparable levels of cognitive function, but differing levels of everyday functional ability, interventions might need to consider targets other than cognition to enhance everyday function (10). In this report, our primary aim was to examine the overall patterns of cognitive function in patients with BD and MDD. Our main hypothesis was that among older adults, BD and MDD would be associated with a similar pattern of deficits, primarily in information processing speed and executive function; however, the level of cognitive impairment would be more severe in individuals with BD. We also predicted that instrumental activities of daily living (IADLs) would be directly related to cognitive performance, most significantly with Information Processing Speed and Executive Function, and IADLs would be more impaired in subjects with BD. These hypotheses were based on our prior reports and the current literature concerning neurodegeneration in BD (11). Exploratory analyses were conducted to examine the relationship of cognition with lifetime history of psychosis and lifetime duration of illness since history of psychosis and longer duration of illness have been associated with worse cognitive function (12).

The growing population of elders is increasing the attention to bipolar disorder (BD) in late life (1, 2). The scant relevant literature highlights the challenges of treating BD in older adults, including greater medical comorbidity and lower tolerance to standard pharmacotherapies than in younger patients (3-6). Evidence specific to geriatric BD is urgently needed (7, 8). While depressive symptoms contribute to reduced quality of life among BD elders (4), there are no published prospective studies of the treatment of geriatric bipolar depression. The challenge of managing bipolar depression in mixed-age populations has been highlighted by previous reports (9-12), and a limited number of medications have been shown to be efficacious for bipolar depression. In addition to the possible precipitation of mania or rapid cycling (13, 14), the addition of multiple psychotropic agents to stabilize mood and treat depression is of concern in older adults due to the risks associated with polypharmacy (15, 16). Lamotrigine was approved by the U.S. Food and Drug Administration for the treatment of epilepsy in 1994, and for the maintenance treatment of BD in 2003. Meta-analysis and meta-regression of monotherapy randomized controlled trials (RCTs) suggest minimal to modest efficacy for lamotrigine in acute bipolar depression (17, 18). However, lamotrigine is widely used in clinical settings for the treatment of bipolar depression, typically in combination with other agents. A recent study of combined lamotrigine and lithium in bipolar depression demonstrated significant improvement and good tolerability in mixed-age adults (19). A literature review and a secondary data-analysis of lamotrigine in older adults with BD (20, 21) suggest that lamotrigine is well tolerated and efficacious, with particular benefit against depressive relapse. The secondary analysis (20) focused on older adults (≥ 55 years) from two placebo-controlled, RCTs evaluating lamotrigine, lithium, and placebo in BD maintenance. There were 638 patients in the double-blind treatment phase including 98 older adults (mean age 61 years, SD = 6.0; range: 55–82 years). Lamotrigine significantly delayed time-to-intervention for depression compared with lithium, while lithium performed better than lamotrigine for time-to-intervention for mania. Side effects for both lamotrigine and lithium were generally time-limited and mild to moderate in intensity, including similar rates of skin rash (3% for lamotrigine, 5% for lithium). Given the positive prospective findings in mixed-age patients and encouraging results in the secondary analysis with older BD patients, we conducted a 12-week, open label trial of lamotrigine in adults age 60 and older with type I or II bipolar depression, assessing its dosing, tolerability, and efficacy. We hypothesized that lamotrigine would be associated with improvement in depressive symptoms and would be well tolerated by these older adults with bipolar depression.

Gildengers AG, Mulsant BH, Al Jurdi RK, Beyer JL, Greenberg RL, Gyulai L, Moberg PJ, Sajatovic M, Ten Have T, Young RC, The GERI-BD Study Group. The relationship of bipolar disorder lifetime duration and vascular burden to cognition in older adults.Bipolar Disord 2010: 12: 851–858. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objectives: We describe the cognitive function of older adults presenting with bipolar disorder (BD) and mania and examine whether longer lifetime duration of BD is associated with greater cognitive dysfunction. We also examine whether there are negative, synergistic effects between lifetime duration of BD and vascular disease burden on cognition. Methods: A total of 87 nondemented individuals with bipolar I disorder, age 60 years and older, experiencing manic, hypomanic, or mixed episodes, were assessed with the Dementia Rating Scale (DRS) and the Framingham Stroke Risk Profile (FSRP) as a measure of vascular disease burden. Results: Subjects had a mean (SD) age of 68.7 (7.1) years and 13.6 (3.1) years of education; 50.6% (n = 44) were females, 89.7% (n = 78) were white, and 10.3% (n = 9) were black. They presented with overall and domain-specific cognitive impairment in memory, visuospatial ability, and executive function compared to age-adjusted norms. Lifetime duration of BD was not related to DRS total score, any other subscale scores, or vascular disease burden. FSRP scores were related to the DRS memory subscale scores, but not total scores or any other domain scores. A negative interactive effect between lifetime duration of BD and FSRP was only observed with the DRS construction subscale. Conclusions: In this study, lifetime duration of BD had no significant relationship with overall cognitive function in older nondemented adults. Greater vascular disease burden was associated with worse memory function. There was no synergistic relationship between lifetime duration of BD and vascular disease burden on overall cognition function. Addressing vascular disease, especially early in the course of BD, may mitigate cognitive impairment in older age.

While age at onset may be useful in explaining some of the heterogeneity of bipolar disorder (BD) in large, mixed age groups, investigations to date have found few meaningful clinical differences between early versus late age at onset in older adults with BD.Data were collected from sixty-one subjects aged 60 years and older, mean (SD) age 67.6 (7.0), with BD I (75%) and II (25%). Subjects were grouped by early (40 years; n = 43) versus late (≥ 40 years; n = 18) age at onset. Early versus late onset groups were compared on psychiatric comorbidity, medical burden, and percentage of days well during study participation.Except for family history of major psychiatric illnesses, there were no differences between the groups on demographic or clinical variables. Patients with early and late onset experienced similar percentages of days well; however, those with early onset had slightly more percentage of days depressed than those with late onset (22% versus 13%)Distinguishing older adults with BD by early or late age at onset has limited clinical usefulness.

More than half of the older adults respond only partially to first-line antidepressant pharmacotherapy. Our objective was to test the hypothesis that a depression-specific psychotherapy, Interpersonal Psychotherapy (IPT), when used adjunctively with escitalopram, would lead to a higher rate of remission and faster resolution of symptoms in partial responders than escitalopram with depression care management (DCM).We conducted a 16-week randomized clinical trial of IPT and DCM in partial responders to escitalopram, enrolling 124 outpatients aged 60 and older. The primary outcome, remission, was defined as three consecutive weekly scores of 7 or less on the Hamilton rating scale for depression (17-item). We conducted Cox regression analyses of time to remission and logistic modeling for rates of remission. We tested group differences in Hamilton depression ratings over time via mixed-effects modeling.Remission rates for escitalopram with IPT and with DCM were similar in intention-to-treat (IPT vs. DCM: 58 [95% CI: 46, 71] vs. 45% [33,58]; p = 0.14) and completer analyses (IPT vs. DCM: 58% [95% CI: 44,72] vs. 43% [30,57]; p = 0.20). Rapidity of symptom improvement did not differ in the two treatments.No added advantage of IPT over DCM was shown. DCM is a clinically useful strategy to achieve full remission in about 50% of partial responders.

This report considers the conceptual and methodological concerns confronting clinical investigators seeking to generate knowledge regarding the tolerability and benefits of pharmacotherapy in geriatric bipolar disorder (BD) patients.There is continuing need for evidence-based guidelines derived from randomized controlled trials that will enhance drug treatment of geriatric BD patients. Therefore, we present the complex conceptual and methodological choices encountered in designing a multisite clinical trial and the decisions reached by the investigators with the intention that study findings be pertinent to, and can facilitate, routine treatment decisions.Guided by a literature review and input from peers, the tolerability and antimanic effects of lithium and valproate were judged to be the key mood stabilizers to investigate with regard to treating bipolar I disorder manic, mixed, and hypomanic states. The patient selection criteria are intended to generate a sample that not only experiences common treatment needs but also represents the variety of older patients seen in university-based clinical settings. The clinical protocol guides titration of lithium and valproate to target serum concentrations, with lower levels allowed when necessitated by limited tolerability. The protocol emphasizes initial monotherapy. However, augmentation with risperidone is permitted after three weeks when indicated by operational criteria.A randomized, controlled trial that both investigates commonly prescribed mood stabilizers and maximizes patient participation can meaningfully address high-priority clinical concerns directly relevant to the routine pharmacologic treatment of geriatric BD patients.

There is substantial evidence that late-life depression can be successfully treated with antidepressant medication.1–3 The benefits of treatment extend beyond patients' improved mood to include lower physical disability,4 better social adjustment,5 and lower healthcare costs.6 Another important but unexamined outcome of depression treatment is less burden on the family caregiver. Although older adults with depression rely on family for assistance and support,7 the burden of providing this care is associated with poorer health and greater risk for mortality in caregivers.8,9 Therefore, alleviating caregiver burden is imperative from a public health perspective and, if achieved through treatment of an elderly person's depression, may also provide a more-complete picture regarding the efficacy of depression treatment. This study was designed to address this issue with family caregivers who were recruited from a study of partial treatment response in late-life major depressive disorder (MDD). The treatment study included 6 weeks of low-dose antidepressant medication for all patients with depression followed by 16 weeks of randomized treatment for patients who had only a partial response to medication at the end of the 6 weeks. Partial response to antidepressant medication at 6 weeks is associated with poorer likelihood of eventual symptom remission in older adults.10,11 The randomized phase of treatment examined whether an increased dose of antidepressant medication combined with interpersonal psychotherapy (IPT) was superior to an increased dose of antidepressant medication alone. Patients showed decreases of approximately 30% in depression ratings during open treatment, but remission rates during randomized treatment were similar in the two randomized groups12 (cumulative response rates of 48–61%). In the current study, it was predicted that decreased depressive symptomatology during open treatment with antidepressant medication would be associated with significantly lower caregiver burden, based on findings from dementia studies showing that cholinesterase inhibitors or antidepressant medication for patients resulted in lower caregiver burden.13,14 The second prediction focused on the randomized treatment phase for partial responders, in which the goal was remission of patient symptoms. It was predicted that caregivers of patients who remitted during randomized treatment would show greater alleviation of burden than caregivers of patients who did not remit. Whether caregivers of patients who received IPT and medication during the randomized phase would show even less burden than caregivers of partial responders who received medication alone was also examined. Greater improvement in caregiver burden may occur as the result of targeting patients' interpersonal problems, which have been shown to hinder family members' efforts to provide care and support when it is needed.15 The focus of this study was on change in two related but unique types of caregiver burden: depression-specific burden and general burden. It was expected that the largest decreases would be found in caregiver burden that was specific to the patients' depressive symptoms and behaviors; the depression subscale from the Revised Memory and Behavior Problems Checklist was used to assess how bothered or upset caregivers were about specific depressive behaviors.16 However, the burden of these family members may also stem from the effects of patient illness on social life, other family responsibilities, and finances. Therefore, the effects of patient improvement on this more general type of caregiver burden were also examined using the Burden Interview.17

The aim of this work was to analyze the sequential foraging behavior of dusky dolphins (Lagenorhynchus obscurus). Foraging sequences were defined when more than two feeding bouts occur with a traveling bout between them. We hypothesized that traveling costs of searching for prey patches were related to the time spent feeding on a patch. In addition, the distribution and seasonal variation of anchovy schools were studied in the area to better understand dolphins’ behavior. We observed dolphins from a research vessel from 2001 to 2007, and recorded their location and behavior. Anchovy data were collected during two hydro-acoustic surveys. Dusky dolphin behaviors varied seasonally; they spent a greater proportion of time traveling and feeding in the warm season (Kruskal-Wallis: H = 172.07, P < 0.01). During the cold season dolphin groups were more likely to exhibit diving behavior and less surface feeding. We found a positive correlation between searching and foraging time (r = 0.88, P = 0.019), suggesting that the costs associated with searching were compensated by an increase in the energy intake during the foraging bout. There was an association between dusky dolphin and anchovy distribution, in that they co-varied spatially and seasonally. Fil: Degrati, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; Argentina. Universidad Nacional de la Patagonia; Argentina Fil: Dans, Silvana Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; Argentina. Universidad Nacional de la Patagonia; Argentina Fil: Garaffo, Griselda Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; Argentina Fil: Cabreira, Ariel Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Subsede Instituto Nacional de Investigación y Desarrollo Pesquero; Argentina Fil: Castro Machado, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Subsede Instituto Nacional de Investigación y Desarrollo Pesquero; Argentina Fil: Crespo, Enrique Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; Argentina. Universidad Nacional de la Patagonia; Argentina

Objective Given the paucity of information available regarding standardized ratings of depression symptoms in bipolar manic states, and in particular those in older adults, we explored depression ratings in symptomatic participants in a multicenter study of treatment of bipolar I disorder in late life. Methods Baseline data was obtained from the first 100 patients enrolled in an NIMH-funded, 9-week, randomized, double-blind RCT comparing treatment with lithium or valproate in patients of age 60 years and older with Type I Bipolar mania or hypomania. This multi-site study was conducted at six academic medical centers in the United States and enrolled inpatients and outpatients with a total Young Mania Rating Scale (YMRS) score of 18 or greater. Depressive symptoms were evaluated with the Hamilton Depression Rating Scale (HAM-D) and the Montgomery-Asberg Depression Rating Scale (MADRS). The criterion for at least moderate bipolar depressive symptoms was the European College of Neuropsychopharmacology (ECNP) Consensus Meeting definition of HAM-D 17 total score >20. Results Eleven percent of patients had mixed symptoms defined by depression scale severity according to ECNP criterion. In the overall sample, total scores on the two depression scales were highly correlated. Total YMRS scores of this mixed symptom group were similar to the remainder of the sample. Conclusions These preliminary findings suggest that moderate to severe depressive symptoms occur in about one in ten bipolar manic elders. Future studies are needed to further evaluate symptom profiles, clinical correlates, and treatments for bipolar older adults with combined manic and depressive symptoms. Copyright © 2011 John Wiley & Sons, Ltd.

OBJECTIVE: Our purpose was to investigate the source and role of elevated levels of immunoreactive β-endorphin in polycystic ovary syndrome. We wished to determine whether immunoreactive β-endorphin secretion in patients with polycystic ovary syndrome is influenced by body weight and whether the pituitary release of immunoreactive β-endorphin with corticotropin-releasing hormone is related to luteinizing hormone levels or adrenal androgen secretion. STUDY DESIGN: Eighteen patients with polycystic ovary syndrome and 10 ovulatory controls were studied. Each subject received 1 μg/kg intravenous corticotropin-releasing hormone and an oral glucose tolerance test on alternate days. Levels of plasma immunoreactive β-endorphin, corticotropin, luteinizing hormone, cortisol, adrenal androgens, and insulin were measured. RESULTS: Although immunoreactive β-endorphin levels were elevated in patients with polycystic ovary syndrome ( p \lt 0.01), incremental responses after corticotropin-releasing hormone were similar to controls and were not influenced by body weight. Serum luteinizing hormone levels were not affected by corticotropin-releasing hormone and did not correlate with immunoreactive β-endorphin levels. Adrenal androgen responses after corticotropin-releasing hormone were increased in patients with polycystic ovary syndrome ( p \lt 0.01) but were not correlated with immunoreactive β-endorphin secretion. After oral glucose was given, elevated fasting insulin levels increased significantly in patients with polycystic ovary syndrome ( p \lt 0.01), as did immunoreactive β-endorphin levels ( p \lt 0.05). The increases in insulin and immunoreactive β-endorphin levels were correlated ( p \lt 0.05). CONCLUSIONS: Pituitary secretion of immunoreactive β-endorphin is normal in patients with polycystic ovary syndrome, and pancreatic secretion appears to be increased. Corticotropin-releasing hormone does not influence luteinizing hormone levels, and adrenal androgen sensitivity is not influenced by immunoreactive β-endorphin secretion. (AM J OBSTET GYNECOL 1992;167:1819-24.)