Safety and anti-tumour activity of the IgE antibody MOv18 in patients with advanced solid tumours expressing folate receptor-alpha: a phase I trial

All antibodies approved for cancer therapy are monoclonal IgGs but the biology of IgE, supported by comparative preclinical data, offers the potential for enhanced effector cell potency. Here we report a Phase I dose escalation trial (NCT02546921) with the primary objective of exploring the safety and tolerability of MOv18 IgE, a chimeric first-in-class IgE antibody, in patients with tumours expressing the relevant antigen, folate receptor-alpha. The trial incorporated skin prick and basophil activation tests (BAT) to select patients at lowest risk of allergic toxicity. Secondary objectives were exploration of anti-tumour activity, recommended Phase II dose, and pharmacokinetics. Dose escalation ranged from 70 μg–12 mg. The most common toxicity of MOv18 IgE is transient urticaria. A single patient experienced anaphylaxis, likely explained by detection of circulating basophils at baseline that could be activated by MOv18 IgE. The BAT assay was used to avoid enrolling further patients with reactive basophils. The safety profile is tolerable and maximum tolerated dose has not been reached, with evidence of anti-tumour activity observed in a patient with ovarian cancer. These results demonstrate the potential of IgE therapy for cancer

X-Ray Spectroscopy of Stars

(abridged) Non-degenerate stars of essentially all spectral classes are soft X-ray sources. Low-mass stars on the cooler part of the main sequence and their pre-main sequence predecessors define the dominant stellar population in the galaxy by number. Their X-ray spectra are reminiscent, in the broadest sense, of X-ray spectra from the solar corona. X-ray emission from cool stars is indeed ascribed to magnetically trapped hot gas analogous to the solar coronal plasma. Coronal structure, its thermal stratification and geometric extent can be interpreted based on various spectral diagnostics. New features have been identified in pre-main sequence stars; some of these may be related to accretion shocks on the stellar surface, fluorescence on circumstellar disks due to X-ray irradiation, or shock heating in stellar outflows. Massive, hot stars clearly dominate the interaction with the galactic interstellar medium: they are the main sources of ionizing radiation, mechanical energy and chemical enrichment in galaxies. High-energy emission permits to probe some of the most important processes at work in these stars, and put constraints on their most peculiar feature: the stellar wind. Here, we review recent advances in our understanding of cool and hot stars through the study of X-ray spectra, in particular high-resolution spectra now available from XMM-Newton and Chandra. We address issues related to coronal structure, flares, the composition of coronal plasma, X-ray production in accretion streams and outflows, X-rays from single OB-type stars, massive binaries, magnetic hot objects and evolved WR stars.Comment: accepted for Astron. Astrophys. Rev., 98 journal pages, 30 figures (partly multiple); some corrections made after proof stag

Association of limbic system-associated membrane protein (LSAMP) to male completed suicide

<p>Abstract</p> <p>Background</p> <p>Neuroimaging studies have demonstrated volumetric abnormalities in limbic structures of suicide victims. The morphological changes might be caused by some inherited neurodevelopmental defect, such as failure to form proper axonal connections due to genetically determined dysfunction of neurite guidance molecules. Limbic system-associated membrane protein (LSAMP) is a neuronal adhesive molecule, preferentially expressed in developing limbic system neuronal dendrites and somata. Some evidence for the association between LSAMP gene and behavior has come from both animal as well as human studies but further investigation is required. In current study, polymorphic loci in human LSAMP gene were examined in order to reveal any associations between genetic variation in <it>LSAMP </it>and suicidal behaviour.</p> <p>Methods</p> <p>DNA was obtained from 288 male suicide victims and 327 healthy male volunteers. Thirty SNPs from LSAMP gene and adjacent region were selected by Tagger algorithm implemented in Haploview 3.32. Genotyping was performed using the SNPlex™ (Applied Biosystems) platform. Data was analyzed by Genemapper 3.7, Haploview 3.32 and SPSS 13.0.</p> <p>Results</p> <p>Chi square test revealed four allelic variants (rs2918215, rs2918213, rs9874470 and rs4821129) located in the intronic region of the gene to be associated with suicide, major alleles being overrepresented in suicide group. However, the associations did not survive multiple correction test. Defining the haplotype blocks using confidence interval algorithm implemented in Haploview 3.32, we failed to detect any associated haplotypes.</p> <p>Conclusion</p> <p>Despite a considerable amount of investigation on the nature of suicidal behaviour, its aetiology and pathogenesis remain unknown. This study examined the variability in LSAMP gene in relation to completed suicide. Our results indicate that LSAMP might play a role in pathoaetiology of suicidal behaviour but further studies are needed to understand its exact contribution.</p

Lesões musculoesqueléticas em policiais militares

INTRODUCTION: The physical qualities need to be analyzed and are risk factors associated with the development of musculoskeletal injuries during military sports training. OBJECTIVE: Epidemiological studies of musculoskeletal injuries occurred in the ankle and foot of military police officers. METHODS: We collected all the medical records of military police officers who have suffered previous injuries in the ankle and foot during the period September 2005 to August 2011. The information was obtained through physical therapy evaluation form found in the records and subsequently the data were tabulated and analyzed. RESULTS: After collecting the data from the medical records, it was found that there 29% bone injuries, 32% ligament injuries and 35% muscle injuries. CONCLUSION: A sprained ankle demonstrates a risk to public health is described by the international statistical classification of diseases and related health problems, which is also in the military environment, described as risk during sports practice.INTRODUCCIÓN: Las cualidades físicas precisan ser analizadas y se vinculan como factores de riesgos para desarrollar lesiones musculoesqueléticas durante el entrenamiento deportivo-militar. OBJETIVO: Recolectar datos sobre epidemiología de las lesiones musculoesqueléticas ocurridas en tobillos y pies de policías militares. MATERIALES Y MÉTODOS: Se analizaron todas las fichas médicas de policías militares que sufrieron lesiones previas en tobillos y pies durante el período de septiembre de 2005 a agosto de 2011; las informaciones fueron obtenidas mediante los formularios de evaluación fisioterapéutica que se encontraban en las fichas médicas; posteriormente, los datos obtenidos fueron tabulados y analizados. RESULTADOS: Después de la recolección de datos de las fichas médicas se observó 29% de lesiones óseas, 32% de ligamentarias y 35% de musculares. CONCLUSIÓN: La torcedura de tobillo demuestra ser un riesgo para la salud pública como se describe en la clasificación estadística internacional de enfermedades y problemas relacionados con la salud, siendo en el medio militar señalada también como un riesgo durante la práctica deportiva.INTRODUÇÃO: As qualidades físicas precisam ser analisadas e estão associadas como fatores de risco a desenvolver lesões musculoesqueléticas durante o treinamento esportivo militar. OBJETIVO: Levantar a epidemiologia das lesões musculoesqueléticas ocorridas em tornozelo e pé de policiais militares. MATERIAIS E MÉTODOS: Foram coletados todos os prontuários de policiais militares que sofreram lesões prévias no tornozelo e pé durante o período de setembro de 2005 a agosto de 2011, as informações foram obtidas através da ficha de avaliação fisioterapêutica constatada nos prontuários, posteriormente os dados obtidos foram tabulados e analisados. RESULTADOS: Após a coleta de dados dos prontuários foi observado que houve 29% de lesões ósseas, 32% de ligamentares e 35% de musculares. CONCLUSÃO: A entorse de tornozelo demonstra um risco à saúde pública como descrita pela classificação estatística internacional de doenças e problemas relacionados à saúde, sendo no meio militar também descrita como um risco durante a prática esportiva.Centro de Reabilitação da Polícia MilitarUniversidade Federal de São Paulo (UNIFESP) Centro de Traumatologia do EsporteUNIFESP, Centro de Traumatologia do EsporteSciEL

Multi-Scale Motility Amplitude Associated with Suicidal Thoughts in Major Depression

Major depression occurs at high prevalence in the general population, often starts in juvenile years, recurs over a lifetime, and is strongly associated with disability and suicide. Searches for biological markers in depression may have been hindered by assuming that depression is a unitary and relatively homogeneous disorder, mainly of mood, rather than addressing particular, clinically crucial features or diagnostic subtypes. Many studies have implicated quantitative alterations of motility rhythms in depressed human subjects. Since a candidate feature of great public-health significance is the unusually high risk of suicidal behavior in depressive disorders, we studied correlations between a measure (vulnerability index [VI]) derived from multi-scale characteristics of daily-motility rhythms in depressed subjects (n = 36) monitored with noninvasive, wrist-worn, electronic actigraphs and their self-assessed level of suicidal thinking operationalized as a wish to die. Patient-subjects had a stable clinical diagnosis of bipolar-I, bipolar-II, or unipolar major depression (n = 12 of each type). VI was associated inversely with suicidal thinking (r =  –0.61 with all subjects and r =  –0.73 with bipolar disorder subjects; both p<0.0001) and distinguished patients with bipolar versus unipolar major depression with a sensitivity of 91.7% and a specificity of 79.2%. VI may be a useful biomarker of characteristic features of major depression, contribute to differentiating bipolar and unipolar depression, and help to detect risk of suicide. An objective biomarker of suicide-risk could be advantageous when patients are unwilling or unable to share suicidal thinking with clinicians

An experimental test of host’s life history traits modulation in response to cuckoo parasitism risk

Hosts can counteract parasites through defences based on resistance and/or tolerance. The mechanistic basis of tolerance, which involve defensive mechanisms minimizing parasite damage after a successful parasitic attack, remains poorly explored in the study of cuckoo-host interactions. Here, we experimentally explore the possibility that the risk of great spotted cuckoo Clamator glandarius parasitism may induce tolerance defences in magpie Pica pica hosts through plasticity in life-history traits. We predict that magpies exposed to auditory cues indicating high parasitism risk will more likely exhibit resistance and/or modify their life-history traits to minimize parasitism costs (i.e. tolerance) compared to magpies under low parasitism risk. We found that manipulating the perceived parasitism risk did not affect host resistance (i.e. rejection of parasitic eggs) nor host life-history traits. Unexpectedly, host's egg volume increased over the season in nests exposed to auditory cues of control non-harmful hoopoes Upupa epops. Our results do not provide support for inducible defences (either based on resistance or tolerance) in response to risk of parasitism in magpie hosts. Even so, we encourage studying plastic expression of breeding strategies in response to risk of cuckoo parasitism to achieve a better understanding of the mechanistic basis of tolerance defences.This work was supported by the Spanish Ministry of Education and Science/FEDER (Projects CGL2011-27561/BOS and CGL2014-56769-P to D. P. and J.M.A.). D.P. was supported by the Government of Extremadura while writing (contract number TA13002). M.E.G. was supported by the Spanish Ministry of Economy and Competitiveness (grant number BES-2012-051898).

Do breast implants after a mastectomy affect subsequent prognosis and survival?

In a large study, published in this issue of Breast Cancer Research, Le and colleagues report that women receiving implants after mastectomies for early-stage breast cancer experience lower breast cancer mortality than women not receiving implants. Assessment of survival patterns among women receiving reconstructive implants is complex given unique patient characteristics, disease attributes, and treatment patterns. The interpretation of reduced mortality from breast cancer must be assessed in light of significantly reduced risks of death from most other causes. In contrast, patients receiving post-mastectomy implants had elevated rates of suicide, consistent with findings among women with cosmetic implants. Additional well-designed investigations are needed to clarify survival patterns among women receiving reconstructive implants