Perinatal outcomes in lesbian couples employing shared motherhood IVF compared with those performing artificial insemination with donor sperm.

STUDY QUESTION: In lesbian couples, is shared motherhood IVF (SMI) associated with an increase in perinatal complications compared with artificial insemination with donor sperm (AID)? SUMMARY ANSWER: Singleton pregnancies in SMI and AID had very similar outcomes, except for a non-significant increase in the rate of preeclampsia/hypertension (PE/HT) in SMI (recipient's age-adjusted odds ratio (OR) = 1.9, 95% CI = 0.7-5.2; P = 0.19), but twin SMI pregnancies had a much higher frequency of PE/HT than AID twins (recipient's age-adjusted OR = 21.7, 95% CI = 2.8-289.4; P = 0.01). WHAT IS KNOWN ALREADY: Oocyte donation (OD) pregnancies are associated with an increase in perinatal complications, in particular, preterm delivery and low birth weight, and PE/HT. However, it is unclear to what extent these complications are due to OD process or to the conditions why OD was performed, such as advanced age and underlying health conditions. Unfortunately, the literature concerning perinatal outcomes in SMI is scarce. STUDY DESIGN, SIZE, DURATION: Retrospective study involving 660 SMI cycles (299 pregnancies) and 4349 AID cycles (949 pregnancies) assisted over a 10-year period. PARTICIPANTS/MATERIALS, SETTING, METHODS: All cycles fulfilling the inclusion criteria performed in lesbian couples seeking fertility treatment in 17 Spanish clinics of the same group. Pregnancy rates of SMI and AID cycles were compared. Perinatal outcomes were compared: gestational length, newborn weight, preterm and low birth rates, PE/HT rates, cesarean section rates, perinatal mortality, and newborn malformations. MAIN RESULTS AND THE ROLE OF CHANCE: Pregnancy rates were higher in SMI than in AID (45.3% versus 21.8%, P < 0.001). There was a non-significant trend to higher multiple rate in AID (4.7% versus 8.5%, P = 0.08). In single pregnancies, there were no differences between SMI and AID in gestational age (278 days (268-285) versus 279 (272-284), P = 0.24), preterm rate (8.3% versus 7.3%, P = 0.80), preterm <28 weeks (0.6% versus 0.4%, P = 1.00), newborn weight (3195 g (2915-3620) versus 3270 g (2980-3600), P = 0.296), low birth rate (6.4% versus 6.4%, P = 1.00), extremely low birth weight (0.6% versus 0.5%, P = 1.00), and the distribution of newborns by weight groups. Cesarean section rate, newborn malformation rate, and perinatal mortality were also similar in SMI and AID. Additionally, there was non-significant trend in hypertensive disorders to an increase in PE/HT among SMI (recipient's age-adjusted OR = 1.9, 95% CI = 0.7-5.2). Overall, perinatal data are consistent with what is reported in the general population. In twin pregnancies, the aforementioned perinatal parameters were also very similar in SMI and AID. However, SMI twin pregnancies had a very high risk of PE/HT when compared with AID (recipient's age-adjusted OR = 21.7, 95% CI = 2.8-289.4, P = 0.01). LIMITATIONS, REASONS FOR CAUTION: Our data regarding the pregnancy course were obtained from information registered in the delivery report as well as from what was reported by the patients themselves, so a certain degree of inaccuracy cannot be ruled out. Additionally, in some parameters, there was up to 10% of data missing. However, since the methodology of reporting was the same in SMI and AID groups, one should not expect a differential reporting bias. It cannot be ruled out that the risk of PE/HT in simple gestations would be significant in a larger study. Additionally, in the SMI group allocation to the transfer of 2 embryos was not randomized so some bias is possible. WIDER IMPLICATIONS OF THE FINDINGS: SMI, if single embryo transfer is performed, seems to be is a safe procedure. Double embryo transfer should not be performed in SMI. Our data suggest that the majority of complications in OD could be related more with recipient status than with OD itself, since with SMI (performed in women without fertility problems) the perinatal complications were much lower than usually described in OD. STUDY FUNDING/COMPETING INTEREST(S): No external funding was received. The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Prevalence of Neospora caninum, Toxoplasma gondii and Brucella abortus in water buffalo (Bubalus bubalis): Climatic and environmental risk factors in eastern and southeast Mexico.

A total of 600 serum samples from five farms were collected and the geographic coordinates of each farm were georeferenced to establish two Köppen climate classes (wet tropical and tropical rainforest). Serum samples were examined by commercially available enzyme-linked immunosorbent assay (ELISA) kits to detect antibodies against N. caninum and T. gondii, while anti-B. abortus antibodies were analysed using the Rose Bengal test and ELISA kit. The overall estimated prevalence of N. caninum, T. gondii and B. abortus was 41.2%, 30.7% and 0.5%, respectively. The highest percentages of positive buffaloes with neosporosis and toxoplasmosis were found in the states of Tabasco (46.7%, wet tropical climate) and Veracruz (32.7%, tropical rainforest climate), respectively. Multivariate logistic regression showed that N. caninum seropositivity in buffalos was associated with the normalized difference vegetation index (NDVI) (OR: 1.068; 95% CI: 1.026-1.112; P = 0.001) and tropical climate regions (OR: 1.737; 95% CI: 1.112-2.712; P = 0.015). In addition, statistical analysis revealed that sex (OR: 1.737, 95% CI: 1.685-9.737; P = 0.002), NDVI (OR: 1.382; 95% CI: 1.095-1.746; P = 0.007) and rainfall (OR: 1.478; 95% CI: 1.110-1.967; P = 0.007) were significant risk factors for T. gondii infections. These results indicate that the potential impact of the risk factors was different for each disease in buffaloes, which may be useful for developing regionally adapted control strategies and preventive measures.

From initial segment to cauda: a regional characterization of mouse epididymal CD11c+ mononuclear phagocytes based on immune phenotype and function.

Successful sperm maturation and storage rely on a unique immunological balance that protects the male reproductive organs from invading pathogens and spermatozoa from a destructive autoimmune response. We previously characterized one subset of mononuclear phagocytes (MPs) in the murine epididymis, CX3CR1+ cells, emphasizing their different functional properties. This population partially overlaps with another subset of understudied heterogeneous MPs, the CD11c+ cells. In the present study, we analyzed the CD11c+ MPs for their immune phenotype, morphology, and antigen capturing and presenting abilities. Epididymides from CD11c-EYFP mice, which express enhanced yellow fluorescent protein (EYFP) in CD11c+ MPs, were divided into initial segment (IS), caput/corpus, and cauda regions. Flow cytometry analysis showed that CD11c+ MPs with a macrophage phenotype (CD64+ and F4/80+) were the most abundant in the IS, whereas those with a dendritic cell signature [CD64- major histocompatibility complex class II (MHCII)+] were more frequent in the cauda. Immunofluorescence revealed morphological and phenotypic differences between CD11c+ MPs in the regions examined. To assess the ability of CD11c+ cells to take up antigens, CD11c-EYFP mice were injected intravenously with ovalbumin. In the IS, MPs expressing macrophage markers were most active in taking up the antigens. A functional antigen-presenting coculture study was performed, whereby CD4+ T cells were activated after ovalbumin presentation by CD11c+ epididymal MPs. The results demonstrated that CD11c+ MPs in all regions were capable of capturing and presenting antigens. Together, this study defines a marked regional variation in epididymal antigen-presenting cells that could help us understand fertility and contraception but also has larger implications in inflammation and disease pathology.

Percepciones de los profesionales sobre la atención prestada, obstáculos y dilemas éticos relacionados con el final de la vida en hospitales, centros de Atención Primaria y residencias de ancianos / Perceptions of health care professionals about end-of-life care, obstacles and ethical dilemmas in hospitals, primary care and nursing homes

Fundamento: Este estudio compara la percepción de la práctica profesional, los obstáculos percibidos y los dilemas éticos de profesionales de medicina y enfermería en la atención al final de la vida en atención primaria (AP), atención hospitalaria (AH) y residencias de ancianos (RA). Material y Métodos: Estudio descriptivo, transversal y multicéntrico. Se realizó un muestreo intencional de profesionales de medicina y enfermería con más de cuatro meses de antigüedad de cuatro hospitales, cinco centros de AP y veintinueve RA de Granada. Se recogieron mediante un cuestionario ad hoc: la percepción de la práctica profesional en ocho dimensiones (estructura y procesos, aspectos físicos, psicológicos, sociales, espirituales, culturales, éticos y cuidados del moribundo), la frecuencia percibida de dilemas éticos, y los obstáculos para el cuidado. Se compararon las puntuaciones de los distintos contextos con la prueba ANOVA y análisis post hoc. Resultados: Participaron 378 profesionales, 215 (56,9%) de AH, 97 (25,7%) de AP y 66 (17,5%) de RA. En comparación a los profesionales de AP y AH, los de RA fueron significativamente (p <0,01) más jóvenes y con mayor experiencia profesional, y puntuaron significativamente mejor (p <0,01) tanto su propia práctica profesional como la de la institución en relación a las dimensiones de estructura y procesos de atención, aspectos físicos, psicológicos, sociales, espirituales, culturales y atención al moribundo. Los aspectos psicológicos y éticos fueron los peor valorados en todos los contextos, no encontrándose diferencias respecto a estos últimos. En comparación a los otros ámbitos estudiados, los profesionales de AP identificaron menos dilemas y los de RA percibieron mayores obstáculos. Conclusiones: Profesionales de AP y AH presentan resultados similares en la percepción de la atención al final de la vida, e inferiores a los de RA, pese a que en las RA se presentan más dilemas y obstáculos

Background: This study compares the perceptions of physicians and nurses regarding professional practice, perceived obstacles and ethical dilemmas in end-of-life care in primary care (PC), hospitals and nursing homes (NH). Methods: Descriptive, cross-sectional and multicentre study. Intentional sampling of physicians and nurses with more than four months professional practice from four hospitals, five PC centres and twenty-nine NH in Granada was carried out. An ad hoc questionnaire was developed to assess perception of professional practice in eight dimensions (structure and processes of care, physical, psychological, social, spiritual, cultural, ethical aspects and care for the dying), frequency of ethical dilemmas, and obstacles to optimum care. Scores of different settings were compared using the ANOVA test and post hoc analysis. Results: A total of 378 professionals participated, 215 (56.9%) from hospitals, 97 (25.7%) from PC and 66 (17.5%) from NH. NH professionals were older and had more professional experience than those from PC and hospitals, and they also rated both the institution and their own professional practice significantly better (p<0.01) than other professionals with respect to the dimensions of structure and processes of care, physical, psychological, social, spiritual, cultural aspects and care for the dying. Psychological and ethical aspects were the worst valued in all settings, with no differences regarding ethical aspects. Fewer ethical dilemmas were identified by PC professionals, while NH professionals perceived greater obstacles to end-of-life care in relation to other settings. Conclusion: Primary care and hospitalization presented similar results on the perception of end-of-life care, and lower results than those of nursing homes, although in these centres more ethical dilemmas and more obstacles were identified

[Perceptions of health care professionals about end-of-life care, obstacles and ethical dilemmas in hospitals, primary care and nursing homes.] / Percepciones de los profesionales sobre la atención prestada, obstáculos y dilemas éticos relacionados con el final de la vida en hospitales, centros de Atención Primaria y residencias de ancianos.

BACKGROUND: This study compares the perceptions of physicians and nurses regarding professional practice, perceived obstacles and ethical dilemmas in end-of-life care in primary care (PC), hospitals and nursing homes (NH). METHODS: Descriptive, cross-sectional and multicentre study. Intentional sampling of physicians and nurses with more than four months professional practice from four hospitals, five PC centres and twenty-nine NH in Granada was carried out. An ad hoc questionnaire was developed to assess perception of professional practice in eight dimensions (structure and processes of care, physical, psychological, social, spiritual, cultural, ethical aspects and care for the dying), frequency of ethical dilemmas, and obstacles to optimum care. Scores of different settings were compared using the ANOVA test and post hoc analysis. RESULTS: A total of 378 professionals participated, 215 (56.9%) from hospitals, 97 (25.7%) from PC and 66 (17.5%) from NH. NH professionals were older and had more professional experience than those from PC and hospitals, and they also rated both the institution and their own professional practice significantly better (p<0.01) than other professionals with respect to the dimensions of structure and processes of care, physical, psychological, social, spiritual, cultural aspects and care for the dying. Psychological and ethical aspects were the worst valued in all settings, with no differences regarding ethical aspects. Fewer ethical dilemmas were identified by PC professionals, while NH professionals perceived greater obstacles to end-of-life care in relation to other settings. CONCLUSION: Primary care and hospitalization presented similar results on the perception of end-of-life care, and lower results than those of nursing homes, although in these centres more ethical dilemmas and more obstacles were identified.

Guía de actuación clínica en la hemorragia subaracnoidea. Sistemática diagnóstica y tratamiento / Clinical practice guidelines for subarachnoid haemorrhage. Diagnosis and treatment

No disponible

Relación entre autoconcepto físico, ansiedad e IMC en estudiantes universitarios mexicanos / The relation of physical self-concept, anxiety, and BMI among Mexican university students

El propósito de la investigación es conocer y relacionar los resultados del autoconcepto físico, con diferentes tipos de ansiedad y el IMC en los estudiantes de enfermería y educación física dela península de Yucatán (México). La muestra estuvo formada por 264 participantes, de los cuales 91 eran varones y 173 mujeres, con edades comprendidas entre 18 y 25 años. Nuestros datos revelan que en el autoconcepto físico, los valores obtenidos por los estudiantes de educación física son superiores al de los estudiantes de enfermería. Los estudiantes de enfermería presentan mayores valores de ansiedad estado que los de educación física. La percepción que tienen los estudiantes de ciclos superiores en prácticamente todas las dimensiones del autoconcepto es superior a la del alumnado de ciclos inferiores. Los niveles de ansiedad disminuyen conforme pasan de ciclos inferiores a superiores (AU)

The purpose of this paper is to know and relate the results of the various dimensions formed by the physical self-concept with respect to the different types of anxiety and the BMI among nursing and physical education students in the area of the Yucatán peninsula in Mexico. The study is based on a sample of 264 people, being 91 men and 173 women between the ages of 18 and 25. The outcome shows that the values obtained by physical education students are higher than those obtained by nursing students regarding the physical self-concept. Nursing students present a higher level of anxiety compared to physical education students. The perception showed by junior and senior students with regard to almost all dimensions of self-concept is higher than that of freshmen and sophomore students. Anxiety level among students decreases throughout the years (AU)

Role and therapeutic value of dendritic cells in central nervous system autoimmunity.

Dendritic cells (DCs) are professional antigen-presenting cells that control the generation of adaptive immunity. Consequently, DCs have a central role in the induction of protective immunity to pathogens and also in the pathogenic immune response responsible for the development and progression of autoimmune disorders. Thus the study of the molecular pathways that control DC development and function is likely to result in new strategies for the therapeutic manipulation of the immune response. In this review, we discuss the role and therapeutic value of DCs in autoimmune diseases, with a special focus on multiple sclerosis.

Clinical management guidelines for subarachnoid haemorrhage. Diagnosis and treatment.

OBJECTIVE: To update the Spanish Society of Neurology's guidelines for subarachnoid haemorrhage diagnosis and treatment. MATERIAL AND METHODS: A review and analysis of the existing literature. Recommendations are given based on the level of evidence for each study reviewed. RESULTS: The most common cause of spontaneous subarachnoid haemorrhage (SAH) is cerebral aneurysm rupture. Its estimated incidence in Spain is 9/100 000 inhabitants/year with a relative frequency of approximately 5% of all strokes. Hypertension and smoking are the main risk factors. Stroke patients require treatment in a specialised centre. Admission to a stroke unit should be considered for SAH patients whose initial clinical condition is good (Grades I or II on the Hunt and Hess scale). We recommend early exclusion of aneurysms from the circulation. The diagnostic study of choice for SAH is brain CT (computed tomography) without contrast. If the test is negative and SAH is still suspected, a lumbar puncture should then be performed. The diagnostic tests recommended in order to determine the source of the haemorrhage are MRI (magnetic resonance imaging) and angiography. Doppler ultrasonography studies are very useful for diagnosing and monitoring vasospasm. Nimodipine is recommended for preventing delayed cerebral ischaemia. Blood pressure treatment and neurovascular intervention may be considered in treating refractory vasospasm. CONCLUSIONS: SAH is a severe and complex disease which must be managed in specialised centres by professionals with ample experience in relevant diagnostic and therapeutic processes.

Influencia del ámbito, rural o urbano, en la percepción de los apoyos y las necesidades de las personas cuidadoras en el hospital / Influence of environment, rural or urban, in the perception of the supports and needs of caregivers in hospitals

Fundamento. Tras implementar un Plan Funcional con medidas de apoyo a personas cuidadoras en dos hospitales de Granada, se analizan la eficacia y el efecto del medio en la percepción y las necesidades de la persona cuidadora. Material y método. Se realizó un estudio cualitativo, fenomenológico, a través de entrevistas semi-estructuradas. Participaron 45 personas cuidadoras incluidas en el Plan Funcional. Se midieron además apoyo social percibido, función familiar y nivel de ansiedad mediante los cuestionarios Duke-unc, Apgar familiar y Escala de Goldberg, respectivamente. El análisis de los datos cualitativos se llevó a cabo mediante codificación abierta, axial y selectiva, y los cuestionarios mediante estadística descriptiva .Resultado. Las personas cuidadoras del ámbito urbano valoraron más los apoyos que les facilitaban la vida en el hospital y los apoyos sociales para el domicilio y las del ámbito rural los apoyos hospitalarios orientados a educación en cuidados para cuando estuviesen en su domicilio, todos ellos vinculados a la personalización de cuidados. Las alteraciones personales por el cuidado están presentes en ambos ámbitos aunque difieren en las repercusiones psíquicas y en el tipo de fármacos y su consumo. Existen diferencias en cuanto a los apoyos necesarios y las dificultades encontradas. Conclusiones. El ámbito donde habitualmente viven las personas cuidadoras condiciona sus percepciones del cuidado y algunas de sus necesidades en el hospital. Se deberán revisar las medidas del Plan Funcional cuestionadas, redefinir algunas prioridades e incluir medidas adicionales en función de la situación familiar de las personas cuidadoras (AU)

Background. After the Functional Plan was implemented with support measures for caregivers in hospitals of Granada (Spain), the effectiveness and impact of environment on the perception and needs of caregivers was analysed. Materials and methods. A qualitative, phenomenological study was made through semi-structured interviews. A total of 45 caregivers included in the Functional Plan participated. In addition, perceived social support, family functioning, and the anxiety level was measured, respectively, through the Duke-UNC, Apgar Family, and Goldberg Scale questionnaires. The data were qualitatively analysed by open, axial, and selective coding, and the questionnaires by descriptive statistics. Results. The caregivers of the urban setting valued more the support that made their life easier in the hospital and the social support at home, while caregivers in rural settings valued the hospital support oriented towards education in care for life after returning home, all linked to the personalization of care. The personal disturbances due to care occurred in all the settings, although differences appeared in psychic repercussions and in the type of drugs and their consumption. There were differences in terms of support needed and the difficulties encountered. Conclusions. The setting where caregivers live determine their perceptions of the care and some of their needs in the hospital. The measures questioned in the Functional Plan should be reviewed and some priorities should be redefined, including additional measures, depending on the family situation of the caregivers (AU)

Suffering indicators in terminally ill children from the parental perspective.

PURPOSE: Suffering is a complex multifaceted phenomenon, which has received limited attention in relation to children with terminal illness. As part of a wider study we interviewed parents of children with terminal illness to elicit their perspectives on suffering, in order to provide initial understanding from which to develop observational indicators and further research. METHODS: Qualitative descriptive study with semi-structured interviews made "ad hoc". Selection through deliberate sampling of mothers and fathers of hospitalised children (0-16 years old) with a terminal illness in Granada (Spain). KEY RESULTS: 13 parents were interviewed. They described children's suffering as manifested through sadness, apathy, and anger towards their parents and the professionals. The isolation from their natural environment, the uncertainty towards the future, and the anticipation of pain caused suffering in children. The pain is experienced as an assault that their parents allow to occur. CONCLUSIONS: The analysis of the interview with the parents about their perception of their ill children's suffering at the end of their lives is a valuable source of information to consider supportive interventions for children and parents in health care settings. An outline summary of the assessed aspects of suffering, the indicators and aspects for health professional consideration is proposed.

Immunological biomarkers: catalysts for translational advances in autoimmune diabetes.

In a recent workshop organized by the JDRF focused on the 'Identification and Utilization of Robust Biomarkers in Type1 Diabetes', leaders in the field of type 1 diabetes (T1D)/autoimmunity and assay technology came together from academia, government and industry to assess the current state of the field, evaluate available resources/technologies and identify gaps that need to be filled for moving the field of T1D research forward. The highlights of this workshop are discussed in this paper, as well as the proposal for a larger, planned consortium effort, incorporating a JDRF Biomarker Core, to foster collaboration and accelerate progress in this critically needed area of T1D research.

Leptin deficiency modulates allograft survival by favoring a Th2 and a regulatory immune profile. [corrected].

Leptin, an adipose-secreted hormone, links metabolism and immunity. Our aim was to determine whether leptin affects the alloimmune response. We used an allogeneic skin transplant model as a means to analyze the allograft immune response in Lep(ob/ob) and wild-type mice. Leptin deficiency results in an increased frequency of Treg and Th2 cells and a prolonged graft survival. These effects of leptin deficiency indicate the importance of leptin and obesity in modulating the allograft immune responses. Our data suggest a possible explanation for the increased susceptibility of hyperleptinemic obese patients to acute and chronic graft rejection.

[Influence of rural or urban environment on perception of the supports and needs of caregivers in hospitals]. / Influencia del ámbito, rural o urbano, en la percepción de los apoyos y las necesidades de las personas cuidadoras en el hospital.

BACKGROUND: After the Functional Plan was implemented with support measures for caregivers in hospitals of Granada (Spain), the effectiveness and impact of environment on the perception and needs of caregivers was analysed. MATERIALS AND METHODS: A qualitative, phenomenological study was made through semi-structured interviews. A total of 45 caregivers included in the Functional Plan took part. In addition, perceived social support, family functioning, and anxiety level were measured, respectively, through the Duke-UNC, Apgar Family, and Goldberg Scale questionnaires. The data were qualitatively analysed by open, axial, and selective coding, and the questionnaires by descriptive statistics. RESULTS: The caregivers of the urban setting valued the support that made their life easier in hospital and the social support received at home more highly, while caregivers in rural settings valued hospital support oriented towards education in care for life after returning home, all linked to the personalization of care. Personal disturbances due to care occurred in all settings, although differences appeared in psychic repercussions and in the type of drugs and their consumption. There were differences in terms of support needed and the difficulties encountered. CONCLUSIONS: The setting where caregivers live determines their perceptions of care and some of their needs in the hospital. The measures questioned in the Functional Plan should be reviewed and some priorities should be redefined, including additional measures, depending on the family situation of the caregivers.

[Spanish Society of Anaesthesia (SEDAR) guidelines for pre-anaesthesia checking procedures]. / Directrices de procedimientos de comprobación y validación («chequeo¼) previos a la anestesia de la Sociedad Española de Anestesiología.

We present this document as a guide to preparing a specific institutional pre-anaesthesia checklist, as recommended in the Helsinki declaration on patient safety in anaesthesiology. Also, the recently recommended WHO "safe surgery check-list" includes a check-list for anaesthesia. A working group was established in accordance with the charter of the Spanish Society of Anaesthesiology and Resuscitation (Sociedad Española de Anestesiología y Reanimación [SEDAR]). The new patient safety culture introduced into medicine, and the recommendations of European anaesthesia societies has led us to design and update protocols in order to improve results in this important part of our speciality. We have prepared these recommendations or guidelines using, as examples, updates of pre-anaesthesia check-lists by other American (ASA), British, or Canadian societies of anaesthesia. With that aim, we enlisted the help of anaesthesia ventilator experts and the participation and advice of experienced anaesthesiologists from all parts of Spain. After various corrections and modifications, the document was available at www.sedar.es, so that any anaesthesiologist could propose any correction, or give their opinion. Finally, these guidelines have been approved by the SEDAR Board of Directors, before it was sent for publication in this journal. The aims of this document are to provide: a guideline applicable to all anaesthesia machines, a descriptive pre-anaesthesia check-list that include everything necessary for the anaesthesia procedure, and a resumed check-list to be available in all the anaesthesia machines or other equivalent, but prepared for each institution, which should include anaesthetic equipment and drugs. So, in order to ensure the aims and requirements of the European Board of Anaesthesiology, the European Society of Anaesthesiology, and the WHO are met, each institution should have a protocol for checking equipment and drugs. These guidelines are applicable to any anaesthesia equipment, enabling every institution to develop their own checking protocols, adapted to their anaesthesia machines and their procedures. With the consent of the SEDAR, this group will collaborate with anaesthesia machines providers in order to develop specific checklists for each of their models that will be available at www.sedar.es.

Antigen microarrays identify CNS-produced autoantibodies in RRMS.

OBJECTIVE: Multiple sclerosis (MS) is characterized by the local production of antibodies in the CNS and the presence of oligoclonal bands in the CSF. Antigen arrays allow the study of antibody reactivity against a large number of antigens using small volumes of fluid with greater sensitivity than ELISA. We investigated whether there were unique autoantibodies in the CSF of patients with MS as measured by antigen arrays and whether these antibodies differed from those in serum. METHODS: We used antigen arrays to analyze the reactivity of antibodies in matched serum and CSF samples of 20 patients with untreated relapsing-remitting MS (RRMS), 26 methylprednisolone-treated patients with RRMS, and 20 control patients with other noninflammatory neurologic conditions (ONDs) against 334 different antigens including heat shock proteins, lipids, and myelin antigens. RESULTS: We found different antibody signatures in matched CSF and serum samples The targets of these antibodies included epitopes of the myelin antigens CNP, MBP, MOBP, MOG, and PLP (59%), HSP60 and HSP70 (38%), and the 68-kD neurofilament (3%). The antibody response in patients with MS was heterogeneous; CSF antibodies in individual patients reacted with different autoantigens. These autoantibodies were locally synthesized in the CNS and were of the immunoglobulin G class. Finally, we found that treatment with steroids decreased autoantibody reactivity, epitope spreading, and intrathecal autoantibody synthesis. CONCLUSIONS: These studies provide a new avenue to investigate the local antibody response in the CNS, which may serve as a biomarker to monitor both disease progression and response to therapy in MS.

Borrowing strength with nonexchangeable priors over subpopulations.

We introduce a nonparametric Bayesian model for a phase II clinical trial with patients presenting different subtypes of the disease under study. The objective is to estimate the success probability of an experimental therapy for each subtype. We consider the case when small sample sizes require extensive borrowing of information across subtypes, but the subtypes are not a priori exchangeable. The lack of a priori exchangeability hinders the straightforward use of traditional hierarchical models to implement borrowing of strength across disease subtypes. We introduce instead a random partition model for the set of disease subtypes. This is a variation of the product partition model that allows us to model a nonexchangeable prior structure. Like a hierarchical model, the proposed clustering approach considers all observations, across all disease subtypes, to estimate individual success probabilities. But in contrast to standard hierarchical models, the model considers disease subtypes a priori nonexchangeable. This implies that when assessing the success probability for a particular type our model borrows more information from the outcome of the patients sharing the same prognosis than from the others. Our data arise from a phase II clinical trial of patients with sarcoma, a rare type of cancer affecting connective or supportive tissues and soft tissue (e.g., cartilage and fat). Each patient presents one subtype of the disease and subtypes are grouped by good, intermediate, and poor prognosis. The prior model should respect the varying prognosis across disease subtypes. The practical motivation for the proposed approach is that the number of accrued patients within each disease subtype is small. Thus it is not possible to carry out a clinical study of possible new therapies for rare conditions, because it would be impossible to plan for sufficiently large sample size to achieve the desired power. We carry out a simulation study to compare the proposed model with a model that assumes similar success probabilities for all subtypes with the same prognosis, i.e., a fixed partition of subtypes by prognosis. When the assumption is satisfied the two models perform comparably. But the proposed model outperforms the competing model when the assumption is incorrect.