Low migratory connectivity and similar migratory strategies in a shorebird with contrasting wintering population trends in Europe and West Africa.

Migratory shorebird populations are declining worldwide, showing an apparent inability to respond to the interplaying challenges emerging along their flyways. Within the East Atlantic Flyway, non-breeding populations show moderate to strong declines in Sub-Saharan Africa, contrasting with stable or increasing trends in Europe. Local factors are insufficient to explain the opposite tendencies and, therefore, investigating migratory strategies and connectivity of these populations may help identifying the drivers of their demography. We followed the migratory journeys of 20 grey plovers (Pluvialis squatarola) from their wintering grounds in Guinea-Bissau (West Africa), Portugal and France (Europe) using tracking devices. Grey plovers wintering in Africa and Europe were found to share breeding grounds at European Russia and Western Siberia, revealing low migratory connectivity in the Eastern Atlantic population. All individuals followed a "skipping" migratory strategy, flying mostly mid-distance bouts, and using an unexpected large network of stopover sites to re-fuel usually for short periods. We identified 66 different stopover sites along the West African, European and Russian/Siberian coasts. All birds stopped at the Wadden Sea in both migratory periods, highlighting the importance of this region and the risk for a potential bottleneck. Low migratory connectivity and similar migratory strategies shared by grey plovers wintering in Europe and West Africa do not support their contrasting population trends.

Long-term trends of salinity in coastal wetlands: Effects of climate, extreme weather events, and sea water level.

Coastal freshwater ecosystems play major roles as reservoirs of biodiversity and provide many ecosystem services and protection from extreme weather events. While they are of particular importance worldwide, they are affected by a large variety of anthropogenic threats, among which salinization has been less studied, particularly regarding large temporal and spatial data sets based on real case scenarios, while salinity can impact biodiversity and ecosystem functioning. In this study, we investigated the variations of salinity across long-term (1996-2020) and seasonal (monthly records) temporal scales and spatial (varying distance to the coastline) scales in water bodies of two typical temperate coastal wetlands situated on the Atlantic coast of France. We complemented our analyses with models of sea water levels computed at both sites across 2000-2020. Our detailed data set allowed for highlighting that salinity in ponds varied seasonally (higher during summer, due to decreased precipitation and higher temperature), but also spatially (higher closer to the seashore, which pattern increased through time). Over the long term, decreased precipitation but not increased temperature induced increasing salinity. We also highlighted contrasted long-term patterns of salinity changes on these two coastal wetlands, with one site were salinity decreased over time linked to the responses to marine flood, allowing to document the temporal dynamics of salinity following a massive intrusion of sea water. Complementarily, at both sites, water levels at high tides increased through time, a pattern which can induce additional salinization. To our knowledge, our study is the first to investigate long-term changes in salinity in coastal wetlands through natural processes (e.g. seaspray, seasonal variations) and ongoing climate perturbations (e.g. marine surges linked to extreme weather events, increased temperature and decreased precipitations).

Behavioral responses to offshore windfarms during migration of a declining shorebird species revealed by GPS-telemetry.

EU member countries and the UK are currently installing numerous offshore windfarms (OWFs) in the Baltic and North Seas to achieve decarbonization of their energy systems. OWFs may have adverse effects on birds; however, estimates of collision risks and barrier effects for migratory species are notably lacking, but are essential to inform marine spatial planning. We therefore compiled an international dataset consisting of 259 migration tracks for 143 Global Positioning System-tagged Eurasian curlews (Numenius arquata arquata) from seven European countries recorded over 6 years, to assess individual response behaviors when approaching OWFs in the North and Baltic Seas at two different spatial scales (i.e. up to 3.5 km and up to 30 km distance). Generalized additive mixed models revealed a significant small-scale increase in flight altitudes, which was strongest at 0-500 m from the OWF and which was more pronounced during autumn than during spring, due to higher proportions of time spent migrating at rotor level. Furthermore, four different small-scale integrated step selection models consistently detected horizontal avoidance responses in about 70% of approaching curlews, which was strongest at approximately 450 m from the OWFs. No distinct, large-scale avoidance effects were observed on the horizontal plane, although they could possibly have been confounded by changes in flight altitudes close to land. Overall, 28.8% of the flight tracks crossed OWFs at least once during migration. Flight altitudes within the OWFs overlapped with the rotor level to a high degree in autumn (50%) but to a significantly lesser extent in spring (18.5%). Approximately 15.8% and 5.8% of the entire curlew population were estimated to be at increased risk during autumn and spring migration, respectively. Our data clearly show strong small-scale avoidance responses, which are likely to reduce collision risk, but simultaneously highlight the substantial barrier effect of OWFs for migrating species. Although alterations in flight paths of curlews due to OWFs seem to be moderate with respect to the overall migration route, there is an urgent need to quantify the respective energetic costs, given the massive ongoing construction of OWFs in both sea areas.

Timing of spring departure of long distance migrants correlates with previous year's conditions at their breeding site.

Precise timing of migration is crucial for animals targeting seasonal resources at locations encountered across their annual cycle. Upon departure, long-distance migrants need to anticipate unknown environmental conditions at their arrival site, and they do so with their internal annual clock. Here, we tested the hypothesis that long-distance migrants synchronize their circannual clock according to the phenology of their environment during the breeding season and therefore adjust their spring departure date according to the conditions encountered at their breeding site the year before. To this end, we used tracking data of Eurasian curlews from different locations and combined movement data with satellite-extracted green-up dates at their breeding site. The spring departure date was better explained by green-up date of the previous year, while arrival date at the breeding site was better explained by latitude and longitude of the breeding site, suggesting that other factors impacted migration timing en route. On a broader temporal scale, our results suggest that long-distance migrants may be able to adjust their migration timing to advancing spring dates in the context of climate change.

Slight variations in coastal topography mitigate the consequence of storm-induced marine submersion on amphibian communities.

The rise in sea-level and the increase in frequency and intensity of extreme weather events (i.e., storms and associated surges) are expected to strongly impact coastal areas. The gradual impacts of sea-level rise may allow species to display adaptive responses to overcome environmental changes. In contrast, the abruptness of marine submersions during extreme weather events can induce changes that may exceed the ability of species to respond to brutally changing environments. Yet, site-specific topographical features may buffer the expected detrimental effects of marine submersions on wildlife. In order to test such topographical effects, we examined the long-term consequences of a major marine submersion (storm Xynthia) on the amphibian communities of two French Atlantic coastal wetlands that slightly differ in their topography and, thus, their susceptibility to marine submersion. Amphibians were monitored on 64 ponds for up to 13 years, using acoustic and visual methods, in conjunction with environmental parameters (e.g., pond topology, vegetation, salinity). We found that the amphibian communities at the two neighboring sites displayed different responses to the marine submersion linked to storm Xynthia. As predicted, slight differences in local topography induced strong differences in local magnitude of the landward marine surge, influencing salinization dynamics and associated consequences on wildlife (amphibians). The different species responses show that amphibian richness can recover to that of pre-storm conditions, but with significant changes in the composition of the community. Our results suggest that amphibian presence post-submersion in coastal wetlands results from an interaction between species traits (e.g., tolerance to elevated salinity), site-specific topography, and environmental parameters. Finally, our study emphasizes that relatively modest landscaping management may be critical to allow wildlife to successfully recover after a marine submersion.

Vaping: Impact of Improving Screening Questioning in Adolescent Population: A Quality Improvement Initiative.

The use of Electronic Nicotine Delivery Systems (ENDS) increased dramatically over the past decade, making them the most common tobacco product used among youth. While physicians often screen for the use of tobacco, very few screen for vaping product usage. This quality improvement project aimed to increase the screening rate of ENDS use among adolescents to 85% to match the Healthy People 2020 screening target of 83.3% for smoking. METHOD: We collected data from weekly chart reviews of all adolescent visits with a primary care provider by using keywords such as "vapor," "e-cigs," and "vaping" to document screening for ENDS use. The project consisted of 4 PDSA cycles: (1) education of the Adolescent Clinic staff about screening; (2) the addition of the specific question for e-cigarette use in the facility's Electronic Health Record; (3) house staff lecture about the importance of screening; and (4) reinforcement about screening to adolescent physicians. RESULTS: The percentage of screening for traditional tobacco use was consistently higher than ENDS use in all months. ENDS use assessment increased since the first intervention, going from 0% at baseline to 90% at the end. The addition of a specific question for ENDS use in EPIC was the most significant intervention and increased the screening percentage to 78%. CONCLUSIONS: To adequately assess for the use of ENDS, the nonspecific question, "do you smoke?" is not sufficient. A direct approach is necessary. A specific question in the EHR is the most significant way to increase screening for ENDS use.

Four-dimensional computed tomography angiography analysis of internal carotid arteries opacification at the skull base to detect delayed cerebral ischemia: a feasibility study.

PURPOSE: Delayed cerebral ischemia represents a significant cause of poor functional outcome for patients with vasospasm after subarachnoid hemorrhage. We investigated whether delayed cerebral ischemia could be detected by the arterial opacification of internal carotid artery at the level of the skull base. METHODS: In this exploratory, nested retrospective cohort diagnostic accuracy study, patients with clinical and/or transcranial Doppler suspicion of vasospasm who underwent four-dimensional computed tomography angiography were included. They were split into two groups for the main endpoint analysis, according to the actually adopted morphological (cerebral infarction) and clinical criteria (neurologic deterioration) of delayed cerebral ischemia. Opacification with a temporal resolution of 0.15 s of both internal carotid arteries at the skull base level was obtained through a semi-automated segmentation method based on skeletonization, and analyzed by a wavelet transform (rbio2.2, level 1). The results obtained by k-means clustering were analyzed with regard to the state of delayed cerebral infarction. RESULTS: Over ten patients included and analyzed, five patients presented a delayed cerebral ischemia, two of them in both side. The semi-automated processing and analysis clustered two different types of opacification curves. The obtaining of a nonlinear opacification pattern was associated (p < 0.001) with delayed cerebral ischemia. CONCLUSIONS: The analysis of arterial opacification of internal carotid arteries at skull base by the proposed processing is feasible and leads to cluster two types of opacification that may help to early detect and prevent delayed cerebral ischemia, in particularly when examinations are artifacted by aneurysm treatment materials.

Cracking the EMDR code: Recruitment of sensory, memory and emotional networks during bilateral alternating auditory stimulation.

INTRODUCTION: The inability to extinguish a conditioned fear is thought to be at the core of post-traumatic stress disorder. Eye movement desensitization and reprocessing therapy has been efficacious for post-traumatic stress disorder, but the brain mechanisms underlying the effect are still unknown. The core effect of eye movement desensitization and reprocessing therapy seems to rely on the simultaneous association of bilateral alternating stimulation and the recall of the traumatic memory. To shed light on how eye movement desensitization and reprocessing therapy functions, we aimed to highlight the structures activated by bilateral alternating stimulation during fear extinction and its recall. METHODS: We included 38 healthy participants in this study. Participants were examined twice in functional magnetic resonance imaging, over 2 consecutive days. On the first day, they performed two fear conditioning and extinction procedures, one with and one without the bilateral alternating stimulation during the fear extinction learning phase in a counter-balanced order across the participants. On the second day, participants completed the fear extinction recall procedure, in the same order as the previous day. Statistical significance of maps was set at p < 0.05 after correction for family-wise error at the cluster level. RESULTS: The analysis revealed significant activation with versus without bilateral alternating stimulation at the early extinction in the bilateral auditory areas, the right precuneus, and the left medial frontal gyrus. The same pattern was found in the early recall on the second day. The connectivity analysis found a significant increase in connectivity during bilateral alternating stimulation versus without bilateral alternating stimulation in the early extinction and recall between the two superior temporal gyri, the precuneus, the middle frontal gyrus and a set of structures involved in multisensory integration, executive control, emotional processing, salience and memory. CONCLUSION: We show for the first time that in the eye movement desensitization and reprocessing therapy the bilateral alternating stimulation is not a simple sensory signal and can activate large emotional neural networks.

Prevalence and risk factors of polycystic ovarian syndrome among an ethnically diverse overweight/obese adolescent population.

BACKGROUND: More remains to be known about polycystic ovary syndrome (PCOS) among overweight/obese adolescents across different ethnicities especially in regards to mental illness as an associated comorbidity. OBJECTIVE: To determine the prevalence of PCOS among overweight and obese adolescents and to evaluate known risk factors for PCOS in a diverse population. METHODS: Charts of patients at an Adolescent Clinic between April 1, 2016 and July 30, 2018 were filtered using: obese, overweight and body mass index (BMI) >85%. Charts were reviewed to identify the presence of PCOS using National Institutes of Health (NIH) criteria, race/ethnicity and known risk factors for PCOS [lipid, BMI, glycated hemoglobin (HA1c), blood pressure (BP)] and mental health conditions associated with PCOS (anxiety/depression and self-harm/suicidal ideation). RESULTS: Patients with PCOS were more likely to have elevated lipids (19.6% vs. 9.9%, p = 0.05), be obese (67.4% vs. 50.9%, p = 0.03), and have acanthosis nigricans (68.9% vs. 28.2%, p =< 0.001). PCOS was more common among non-Hispanic patients (77.9%) vs. Hispanic patients (57.8%). There was no difference in the prevalence of depression/anxiety (37% vs. 33%, respectively, p = 0.590) or self - harm/suicidal ideation (17% vs. 17%, p = 0.96) in patients with and without PCOS. In a logistic regression model, after adjusting for all demographics and clinical features, ethnicity, acanthosis nigricans and BMI were significant risk factors for PCOS. CONCLUSION: Patients with PCOS are more likely to be obese, hyperlipidemic, have acanthosis nigricans and be of non-Hispanic ethnicity. However, there was no difference in the prevalence of depression/anxiety and self-harm/suicidal ideation among adolescents with or without PCOS.

Posttraumatic Stress Disorder is associated with altered reward mechanisms during the anticipation and the outcome of monetary incentive cues.

BACKGROUND: Recent studies suggest that Posttraumatic Stress Disorder (PTSD) might be associated with dysfunctional reward circuitry. However, further research is needed to understand the key role of the reward system in PTSD symptomatology. METHODS: Twenty participants with PTSD and 21 Trauma-Exposed matched Controls (TECs) completed the Monetary Incentive Delay (MID) task during an MRI session. Reaction times (RTs) and hit rates were recorded. Brain activity was investigated during the anticipation and the outcome of monetary gains and losses. RESULTS: During the anticipation of monetary loss, PTSD participants had higher RTs than TECs. However, the groups did not differ at the neurofunctional level. During successful avoidance of monetary loss, PTSD patients showed higher activation than TECs in the left caudate nucleus. During the anticipation of monetary gains, no differences in RTs were found between groups. PTSD patients had specific activations in the right amygdala, nucleus accumbens, putamen, and middle frontal gyrus (p < 0.05 family-wise error (FWE)-corrected), while TECs had specific activation in the anterior cingulate cortex. When obtaining monetary gains, PTSD patients had specific activation in the caudate nucleus, while TECs had specific activations in the right hypothalamus, subthalamic nucleus, and left inferior frontal gyrus. CONCLUSION: For the first time, functional brain activation during both the anticipation and the outcome of monetary rewards is reported altered in PTSD patients. These alterations might be associated with the complex symptomatology of PTSD.

Fear extinction learning improvement in PTSD after EMDR therapy: an fMRI study.

Objective: Neurobiological models of Posttraumatic Stress Disorder (PTSD) implicate fear processing impairments in the maintenance of the disorder. Eye Movement Desensitization and Reprocessing (EMDR) is one of the most efficient psychotherapies to treat PTSD. We aimed at exploring the brain mechanisms of the fear circuitry involved in PTSD patients' symptom remission after EMDR therapy. Method: Thirty-six PTSD participants were randomly assigned to either EMDR group receiving EMDR therapy or Wait-List (WL) group receiving supportive therapy. Participants underwent a behavioural fear conditioning and extinction paradigm during functional magnetic resonance (fMRI). In the EMDR group, patients were scanned at baseline, before EMDR and one week after remission. In the WL group, patients were scanned at baseline and within the same time interval as the EMDR group. Results: In the EMDR group after treatment, fear responses in the late extinction were significantly lower than before therapy. In parallel, significant functional activity and connectivity changes were found in the EMDR group versus the WL during the late extinction. These changes involve the fear circuit (amygdalae, left hippocampus), the right inferior frontal gyrus, the right frontal eye field and insula (pFWE < .05). Conclusion: These functional modifications underlie a significant improvement of fear extinction learning in PTSD patients after EMDR therapy.

Objetivo: Los modelos neurobiológicos del TEPT implican deficiencias en el procesamiento del miedo en el mantenimiento del trastorno. EMDR es una de las psicoterapias más eficaces para tratar el TEPT. Nuestro objetivo fue explorar los mecanismos cerebrales de los circuitos de miedo implicados en la remisión de los síntomas de los pacientes con el TEPT después de la terapia EMDR.Método: Treinta y seis participantes con el TEPT fueron asignados aleatoriamente a un grupo EMDR que recibió terapia EMDR o un grupo de Lista de Espera (LE) que recibió terapia de apoyo. Los participantes se sometieron a un paradigma de condicionamiento y extinción del miedo conductual durante la resonancia magnética funcional (fMRI). En el grupo EMDR, los pacientes fueron escaneados al inicio del estudio, antes de EMDR y una semana después de la remisión. En el grupo LE, los pacientes fueron escaneados al inicio y en el mismo intervalo de tiempo que el grupo EMDR.Resultados: En el grupo EMDR después del tratamiento, las respuestas de miedo en la extinción tardía fueron significativamente más bajas que antes de la terapia. En paralelo, se encontraron cambios significativos en la actividad funcional y en la conectividad en el grupo EMDR v/s el grupo LE durante la extinción tardía. Estos cambios involucran el circuito de miedo (amígdala, hipocampo izquierdo), el giro frontal inferior derecho, los campos del ojo frontal derecho y la ínsula (pFWE < .05).Conclusión: Estas modificaciones funcionales subyacen a una mejora significativa del aprendizaje de extinción del miedo en pacientes con el TEPT después de la terapia EMDR.

Tracing changes in the diet and habitat use of black-tailed godwits in Western France, using a stable isotope approach.

Western France is at the crossroads of the migratory routes of two subspecies of black-tailed godwit, Limosa limosa. After leaving Iceland, the godwit L.l. islandica Icelandic black-tailed godwit (IBTG) winters on the coast of western Europe, while the continental black-tailed godwit (CBTG) L.l. limosa can stop in France when migrating between Iberia or Africa and their main breeding grounds in the Netherlands. In this study, we analysed δ15N and δ13C from flight feathers and whole blood throughout the non-breeding period to trace variations in habitat use for both subspecies on the western French coast. Adults and juveniles of IBTG adopt the same feeding habitats as soon as they arrive in the study area, progressively losing the Icelandic freshwater habitat signal, and becoming clearly restricted to marine habitats in winter. Some individuals begin to move locally to freshwater habitats, joining CBTG in a stopover at the end of the wintering period in preparation for northward migration.

Grey matter density changes of structures involved in Posttraumatic Stress Disorder (PTSD) after recovery following Eye Movement Desensitization and Reprocessing (EMDR) therapy.

Recovery of stress-induced structural alterations in Posttraumatic Stress Disorder (PTSD) remains largely unexplored. This study aimed to determine whether symptoms improvement is associated with grey matter (GM) density changes of brain structures involved in PTSD. Two groups of PTSD patients were involved in this study. The first group was treated with Eye Movement Desensitization and Reprocessing (EMDR) therapy and recovered from their symptoms (recovery group) (n = 11); Patients were scanned prior to therapy (T1), one week (T2) and five months after the end of therapy (T3). The second group included patients which followed a supportive therapy and remained symptomatic (wait-list group) (n = 7). They were scanned at three time-steps mimicking the same inter-scan intervals. Voxel-based morphometry (VBM) was used to characterize GM density evolution. GM density values showed a significant group-by-time interaction effect between T1 and T3 in prefrontal cortex areas. These interaction effects were driven by a GM density increase in the recovery group with respect to the wait-list group. Symptoms removal goes hand-in-hand with GM density enhancement of structures involved in emotional regulation.

Bilateral Alternating Auditory Stimulations Facilitate Fear Extinction and Retrieval.

Disruption of fear conditioning, its extinction and its retrieval are at the core of posttraumatic stress disorder (PTSD). Such deficits, especially fear extinction delay, disappear after alternating bilateral stimulations (BLS) during eye movement desensitization and reprocessing (EMDR) therapy. An animal model of fear recovery, based on auditory cued fear conditioning and extinction learning, recently showed that BLS facilitate fear extinction and fear extinction retrieval. Our goal was to determine if these previous results found in animals can be reproduced in humans. Twenty-two healthy participants took part in a classical fear conditioning, extinction, and extinction recall paradigm. Behavioral responses (fear expectations) as well as psychophysiological measures (skin conductance responses, SCRs) were recorded. The results showed a significant fear expectation decrease during fear extinction with BLS. Additionally, SCR for fear extinction retrieval were significantly lower with BLS. Our results demonstrate the importance of BLS to reduce negative emotions, and provide a successful model to further explore the neural mechanisms underlying the sole BLS effect in the EMDR.

The Moro reaction: More than a reflex, a ritualized behavior of nonverbal communication.

OBJECTIVE: To propose a phylogenetic significance to the Moro reflex which remains unexplained since its publication in 1918 because both hands are free at the end of the gesture. METHOD: Among the 75 videos of healthy term newborns we have filmed in a research project on antenatal education to parenthood, we describe a sequence that clearly showed the successive movements of the Moro reflex and we report the occurrence of this reflex in the videos that were recorded from Time 0 of birth defined as the moment that lies between the birth of the thorax and the pelvis of the infant. RESULTS: The selected sequence showed the following succession of the newborn's actions: quick extension-adduction of both arms, the orientation of the body, head and eyes towards a human person, and full extension-abduction of both arms with spreading of the fingers, crying and a distressed face. There were 13 Moro reflexes between 2 and 14s from Time 0 of birth. We found a significant association between the occurrence of the Moro reflex and the placement of the newborn at birth in supine position on the mother's abdomen (p=0.002). DISCUSSION: The quick extension-adduction of both arms which started the sequence may be considered as a startle reflex controlled by the neural fear system and the arm extension-adduction which followed as a Moro reflex. The characteristics of all Moro reflexes were those of ritualization: amplitude, duration, stereotype of the gestures. This evolutionary process turns a physiological behavior, grasping in this case, to a non-verbal communicative behavior whose meaning is a request to be picked up in the arms. The gestures associated with the Moro reflex: crying and orientation of the body, head, and eyes towards a human person, are gestures of intention to communicate which support our hypothesis. The neural mechanism of the Moro reaction probably involves both the fear and the separation-distress systems. CONCLUSION: This paper proposes for the first time a phylogenetic significance to the Moro reflex: a ritualized behavior of nonverbal communication. Professionals should avoid stimulating the newborns' fear system by unnecessarily triggering Moro reflexes. Antenatal education should teach parents to respond to the Moro reflexes of their newborn infant by picking her up in their arms with mother talk.

Childhood trauma and emotional processing circuits in schizophrenia: A functional connectivity study.

Childhood trauma strongly impacts emotional responses in schizophrenia. We have explored an association between early trauma and the amygdala functional connectivity using generalized psychophysiological interaction during an emotional task. Twenty-one schizophrenia patients and twenty-five controls were included. In schizophrenia patients, higher levels of sexual abuse and physical neglect during childhood were associated with decreased connectivity between the amygdala and the posterior cingulate/precuneus region. Additionally, patients showed decreased coupling between the amygdala and the posterior cingulate/precuneus region compared to controls. These findings suggest that early trauma could impact later connectivity in specific stress-related circuits affecting self-consciousness and social cognition in schizophrenia.

A Phase II feasibility study of oral etoposide given concurrently with radiotherapy followed by dose intensive adjuvant chemotherapy for children with newly diagnosed high-risk medulloblastoma (protocol POG 9631): A report from the Children's Oncology Group.

BACKGROUND: Children with high-risk medulloblastoma historically have had a poor prognosis. The Children's Oncology Group completed a Phase II study using oral etoposide given with radiotherapy followed by intensive chemotherapy. PROCEDURE: Patients enrolled in the study had high-risk disease defined as ≥1.5 cm2 of residual disease postsurgery or definite evidence of central nervous metastasis. All patients underwent surgery followed by radiotherapy. During radiation, the patients received oral etoposide (21 days on, 7 off) at an initial dose of 50 mg/m2 per day (treatment 1), which was reduced to 35 mg/m2 per day (treatment 2) due to toxicity. After radiotherapy, the patients received chemotherapy with three cycles of cisplatin and oral etoposide, followed by eight courses of cyclophosphamide and vincristine. RESULTS: Between November 1998 and October 2002, 53 patients were accrued; 15 received treatment 1 and 38 treatment 2. Forty-seven patients (89%) were eligible. Response to radiation was excellent, with 19 (40.4%) showing complete response, 24 (51.1%) partial response, and four (8.5%) no recorded response. The overall 2- and 5-year progression-free survival (PFS) was 76.6 ± 6% and 70.2 ± 7%, respectively. The 2- and 5-year overall survival (OS) was 80.9 ± 6% and 76.6 ± 6%, respectively. Clinical response postradiation and PFS/OS were not significantly different between the treatment groups. There was a trend toward a difference in 5-year PFS between those without and with metastatic disease (P = 0.072). CONCLUSIONS: Oral etoposide was tolerable at 35 mg/m2 (21 days on and 7 days off) when given during full-dose irradiation in patients with high-risk medulloblastoma with encouraging survival data.

Treatment of Post-Traumatic Stress Disorders with the Alpha-1 Adrenergic Antagonist Prazosin.

OBJECTIVE: The present review aims to assess the clinical efficacy and safety of the α-1-adrenergic antagonist prazosin as primary pharmacologic treatment for post-traumatic stress disorder (PTSD). METHOD: A systematic review was performed using keywords (i.e., prazosin, α-1-adrenergic antagonist, α-1-blocker, post-traumatic stress disorder) in the databases PubMed/Medline (1966-May 2016), Embase (1966-May 2016), ScienceDirect (1823-May 2016), OvidSP (1946-May 2016) and Nature (1845-May 2016). To be considered for inclusion, studies had to test the efficacy of prazosin either alone or added to ongoing treatment in adults with PTSD, use validated tools to assess and monitor the disorders, allow comparisons on the basis of univariate analyses (i.e., p-values of t-tests and effect sizes) and list the identified adverse reactions. RESULTS: 12 studies were included: 5 randomized controlled trials, 4 open-label prospective trials and 3 retrospective file reviews. The evaluation concerned 276 patients exposed to civilian trauma (19%) or war trauma (81%). Prazosin significantly decreases trauma nightmares, avoidance, hypervigilance and improves patient status in all studies. No significant difference of blood pressure was observed at the end of trials. CONCLUSIONS: Beyond the methodological and clinical biases of these studies, the present review not only confirms the effectiveness and good tolerability of prazosin, but also suggests its possible use as primary pharmacologic treatment for PTSD. Uncertainties remain, however, regarding the prescription modalities and dosages.

Regional Nodal Irradiation in Early-Stage Breast Cancer.

BACKGROUND: Most women with breast cancer who undergo breast-conserving surgery receive whole-breast irradiation. We examined whether the addition of regional nodal irradiation to whole-breast irradiation improved outcomes. METHODS: We randomly assigned women with node-positive or high-risk node-negative breast cancer who were treated with breast-conserving surgery and adjuvant systemic therapy to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph nodes) (nodal-irradiation group) or whole-breast irradiation alone (control group). The primary outcome was overall survival. Secondary outcomes were disease-free survival, isolated locoregional disease-free survival, and distant disease-free survival. RESULTS: Between March 2000 and February 2007, a total of 1832 women were assigned to the nodal-irradiation group or the control group (916 women in each group). The median follow-up was 9.5 years. At the 10-year follow-up, there was no significant between-group difference in survival, with a rate of 82.8% in the nodal-irradiation group and 81.8% in the control group (hazard ratio, 0.91; 95% confidence interval [CI], 0.72 to 1.13; P=0.38). The rates of disease-free survival were 82.0% in the nodal-irradiation group and 77.0% in the control group (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P=0.01). Patients in the nodal-irradiation group had higher rates of grade 2 or greater acute pneumonitis (1.2% vs. 0.2%, P=0.01) and lymphedema (8.4% vs. 4.5%, P=0.001). CONCLUSIONS: Among women with node-positive or high-risk node-negative breast cancer, the addition of regional nodal irradiation to whole-breast irradiation did not improve overall survival but reduced the rate of breast-cancer recurrence. (Funded by the Canadian Cancer Society Research Institute and others; MA.20 ClinicalTrials.gov number, NCT00005957.).

Effect of trait anxiety on prefrontal control mechanisms during emotional conflict.

Converging evidence points to a link between anxiety proneness and altered emotional functioning, including threat-related biases in selective attention and higher susceptibility to emotionally ambiguous stimuli. However, during these complex emotional situations, it remains unclear how trait anxiety affects the engagement of the prefrontal emotional control system and particularly the anterior cingulate cortex (ACC), a core region at the intersection of the limbic and prefrontal systems. Using an emotional conflict task and functional magnetic resonance imaging (fMRI), we investigated in healthy subjects the relations between trait anxiety and both regional activity and functional connectivity (psychophysiological interaction) of the ACC. Higher levels of anxiety were associated with stronger task-related activation in ACC but with reduced functional connectivity between ACC and lateral prefrontal cortex (LPFC). These results support the hypothesis that when one is faced with emotionally incompatible information, anxiety leads to inefficient high-order control, characterized by insufficient ACC-LPFC functional coupling and increases, possibly compensatory, in activation of ACC. Our findings provide a deeper understanding of the pathophysiology of the neural circuitry underlying anxiety and may offer potential treatment markers for anxiety disorders.