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INTRODUCTION: In recent years, primary surgical treatment of older women with non-metastatic breast cancer has decreased in favor of primary endocrine therapy (PET). PET can be considered in women with a remaining life expectancy of less than five years. The aim of this study was to (1) assess the risk of distant metastases and other cause mortality over ten years in women aged 65 and older with stage I-III breast cancer treated with PET, (2) whether this was associated with geriatric characteristics and comorbidities and to (3) describe the reasons on which the choice for PET was made. METHODS: Women were included from the retrospective FOCUS cohort, which comprises all incident women diagnosed with breast cancer aged 65 or older between January 1997 and December 2004 in the Comprehensive Cancer Center Region West in the Netherlands. We selected women (N = 257) with stage I-III breast cancer and treated with PET from this cohort. Patient characteristics (including comorbidity, polypharmacy, walking, cognitive and sensory impairment), treatment and tumor characteristics were retrospectively extracted from charts. Outcomes were distant metastasis and other cause mortality. Cumulative incidences were calculated using the Cumulative Incidence for Competing Risks method (CICR); and subdistribution hazard ratios (SHR) were tested between groups based on age, geriatric characteristics and comorbidity with the Fine and Gray model. RESULTS: Women treated with PET were on average 84 years old and 41% had one or more geriatric characteristics. Other cause mortality exceeded the cumulative incidence of distant metastasis over ten years (83 versus 5.6%). The risk of dying from another cause further increased in women with geriatric characteristics (SHR 2.06, p < 0.001) or two or more comorbidities (SHR 1.72, p < 0.001). Often the reason for omitting surgery was not recorded (52.9%), but if recorded surgery was omitted mainly at the patient's request (18.7%). DISCUSSION: This study shows that the cumulative incidence of distant metastasis is much lower than other cause mortality in older women with breast cancer treated with PET, especially in the presence of geriatric characteristics or comorbidities. This confirms the importance of assessment of geriatric characteristics to aid counseling of older women.
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Neoplasias de la Mama , Femenino , Humanos , Anciano , Anciano de 80 o más Años , Estudios Retrospectivos , Neoplasias de la Mama/tratamiento farmacológico , Comorbilidad , Esperanza de Vida , Países Bajos/epidemiologíaRESUMEN
BACKGROUND: Ecological momentary assessment (EMA) is a promising method to gain insight into the daily lives of people with mental disorders. EMA can be used to monitor mood, symptoms, and experiences multiple times per day. Using advanced statistical methods, such as network analysis, as EMA feedback might result in novel insights that are relevant to psychiatric care. AIM: To investigate the promise, pitfalls, and possibilities of EMA and network analysis for psychiatric care. METHOD: Empirical network studies, reviews, and qualitative research were employed to investigate the state of research and the perspectives of patients and clinicians on EMA and network analysis. Furthermore, an empirical study will be discussed, in which twenty patients with bipolar disorders completed five EMA diaries per day for four months within treatment. RESULTS: Studies using network analysis demonstrated conflicting results. Qualitative research indicated that bipolar patients and clinicians are aware of the added benefit of EMA for psychiatric care, especially for improving insight and self-management. At the same time, EMA was seen as burdensome. Personalization and integration with existing treatment protocols emerged as necessary requirements for adequate implementation of EMA in psychiatric care. CONCLUSION: EMA can have added value for psychiatric care, provided it is adequately implemented. BACKGROUND: Ecological momentary assessment (EMA) is a promising method to gain insight into the daily lives of people with mental disorders. EMA can be used to monitor mood, symptoms, and experiences multiple times per day. Using advanced statistical methods, such as network analysis, as EMA feedback might result in novel insights that are relevant to psychiatric care. AIM: To investigate the promise, pitfalls, and possibilities of EMA and network analysis for psychiatric care. METHOD: Empirical network studies, reviews, and qualitative research were employed to investigate the state of research and the perspectives of patients and clinicians on EMA and network analysis. Furthermore, an empirical study will be discussed, in which twenty patients with bipolar disorders completed five EMA diaries per day for four months within treatment. RESULTS: Studies using network analysis demonstrated conflicting results. Qualitative research indicated that bipolar patients and clinicians are aware of the added benefit of EMA for psychiatric care, especially for improving insight and self-management. At the same time, EMA was seen as burdensome. Personalization and integration with existing treatment protocols emerged as necessary requirements for adequate implementation of EMA in psychiatric care. CONCLUSION: EMA can have added value for psychiatric care, provided it is adequately implemented.
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Trastorno Bipolar , Psiquiatría , Automanejo , Humanos , Evaluación Ecológica Momentánea , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/terapia , PsicoterapiaRESUMEN
PURPOSE: Treatment of head and neck cancer (HNC) carries a high risk of adverse outcomes in patients, especially in frail elderly. Therefore, it is important to identify patients in which treatment benefits outweigh the risk of any adverse outcome. Although the comprehensive geriatric assessment (CGA) identifies frailty, it is a time-consuming tool. Instead, measurement of skeletal muscle mass and strength (sarcopenia) may be a promising and time-efficient biomarker for frailty. The aim of this study was to examine the association between sarcopenia and frailty assessment tools, such as the CGA, Fried criteria and the Groningen Frailty Indicator (GFI). METHODS: A retrospective study was performed in elderly patients (≥ 70-years) with HNC. Sarcopenia was defined as the combination of reduced handgrip strength (HGS) and low skeletal muscle mass (SMM), according to the EWGSOP-2 criteria. SMM was measured on routinely available diagnostic imaging and corrected height: skeletal muscle index (SMI). A CGA was performed by a geriatrician. Frailty screening was performed using the GFI and the Fried criteria. RESULTS: In total, 73 patients were included of which 33 were men (45.2%) and 40 women (54.8%). Frail patients diagnosed by CGA were more likely to have low SMI, sarcopenia, more comorbidities and were at high risk for malnutrition (all p < 0.05). In multivariate regression analysis, the only significant predictor for frailty diagnosed by CGA was SMI (OR 0.9, p < 0.01) independent of comorbidity and muscle strength. CONCLUSION: Low SMI and sarcopenia are associated with frailty in elderly HNC patients. Low SMI predicts frailty and is a promising time-efficient and routinely available tool for clinical practice.
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Fragilidad , Neoplasias de Cabeza y Cuello , Anciano , Femenino , Fragilidad/diagnóstico , Fragilidad/epidemiología , Evaluación Geriátrica , Fuerza de la Mano , Neoplasias de Cabeza y Cuello/complicaciones , Humanos , Masculino , Músculo Esquelético , Estudios RetrospectivosRESUMEN
INTRODUCTION: Over the past few years, 3D printing has evolved rapidly. This has resulted in an increasing number of scientific publications reporting on the medical use of 3D printing. These applications can range from patient information, preoperative planning, education, or 3D printing of patient-specific surgical implants. The objective of this review was to give an overview of the different applications in urology and other disciplines based on a selection of publications. METHODS: In the current narrative review the Medline database was searched to identify all the related reports discussing the use of 3D printing in the medical field and more specifically in Urology. 3D printing applications were categorized so they could be searched more thoroughly within the Medline database. RESULTS: Three-dimensional printing can help improve pre-operative patient information, anatomy and medical trainee education. The 3D printed models may assist the surgeon in preoperative planning or become patient-specific surgical simulation models. In urology, kidney cancer surgery is the most concerned by 3D printing-related publications, for preoperative planning, but also for surgical simulation and surgical training. CONCLUSION: 3D printing has already proven useful in many medical applications, including urology, for patient information, education, pre-operative planning and surgical simulation. All areas of urology are involved and represented in the literature. Larger randomized controlled studies will certainly allow 3D printing to benefit patients in routine clinical practice.
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Neoplasias Renales , Urología , Humanos , Riñón , Modelos Anatómicos , Impresión TridimensionalRESUMEN
Partial nephrectomy is a first-line treatment option for the management of renal tumors. It is a surgical procedure whose complexity and stakes vary according to the specific anatomy of the patient and his tumor. 3D modeling and 3D printing have become a means of representing and thus visualizing the tumor lesion and its anatomical relationships within the organ. This mode of visualization allows the surgeon and his team, but also the patient, to easily realize the tumor complexity, the predictable difficulty of the surgery and therefore the risks of complications. Various publications have reported the benefit to the patient in terms of pre-therapy education. Some have shown a benefit for the operator in terms of surgical planning. Finally, studies on preoperative surgical simulation showed shorter kidney lumpectomy times and less bleeding when surgeons were able to train before the operation on the corresponding 3D printed model. 3D printing therefore represents an innovative tool that would improve patient management prior to partial nephrectomy, through the information it can deliver, but also through surgical simulation.
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Neoplasias Renales/cirugía , Modelos Anatómicos , Nefrectomía/métodos , Modelación Específica para el Paciente , Impresión Tridimensional , HumanosRESUMEN
INTRODUCTION: VMS is a Dutch risk assessment tool for hospitalized older adults that includes a short evaluation of four geriatric domains: risk for delirium, risk for undernutrition, risk for physical impairments, and fall risk. We investigated whether the information derived from this tool has prognostic value for outcomes of colorectal surgery. METHODS: All consecutive patients over age 70 years who underwent elective colorectal cancer surgery in three Dutch hospitals (2014-2016) were studied. The presence of risk was scored prior to surgery and per geriatric domain as either 0 (risk absent) or 1 (risk present). The total number of geriatric risk factors was summed. The primary outcome was long-term survival. Secondary outcomes were postoperative complications, including delirium. Cox proportional hazards models were used to evaluate the sumscore and risk factors associated with overall survival. RESULTS: Five hundred fifty patients were included. Median age was 76.5 years, and median follow-up was 870 days. Patients with intermediate (1-2) or high (3-4) sumscore were independently associated with lower overall survival, with hazard ratio (HR) of 1.9 [95% confidence interval (CI) 1.1-3.5; p = 0.03] and 8.7 (95% CI 4.0-19.2; p < 0.001), respectively. Sumscores were also associated with postoperative complications (intermediate sumscore OR 1.8; 95% CI 1.2-2.7; high sumscore OR 2.4; 95% CI 1.02-5.5). CONCLUSIONS: This easy-to-use geriatric sumscore has strong associations with long-term outcome and morbidity after colorectal cancer surgery. This information may be included in risk models for morbidity and mortality and can be used in shared decision-making.
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Neoplasias Colorrectales/cirugía , Cirugía Colorrectal/efectos adversos , Delirio/mortalidad , Procedimientos Quirúrgicos Electivos/efectos adversos , Complicaciones Posoperatorias/mortalidad , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/patología , Delirio/etiología , Femenino , Estudios de Seguimiento , Evaluación Geriátrica , Humanos , Masculino , Complicaciones Posoperatorias/etiología , Pronóstico , Medición de Riesgo , Tasa de SupervivenciaRESUMEN
High-energy neutrino emission has been predicted for several short-lived astrophysical transients including gamma-ray bursts (GRBs), core-collapse supernovae with choked jets, and neutron star mergers. IceCube's optical and x-ray follow-up program searches for such transient sources by looking for two or more muon neutrino candidates in directional coincidence and arriving within 100 s. The measured rate of neutrino alerts is consistent with the expected rate of chance coincidences of atmospheric background events and no likely electromagnetic counterparts have been identified in Swift follow-up observations. Here, we calculate generic bounds on the neutrino flux of short-lived transient sources. Assuming an E^{-2.5} neutrino spectrum, we find that the neutrino flux of rare sources, like long gamma-ray bursts, is constrained to <5% of the detected astrophysical flux and the energy released in neutrinos (100 GeV to 10 PeV) by a median bright GRB-like source is <10^{52.5} erg. For a harder E^{-2.13} neutrino spectrum up to 30% of the flux could be produced by GRBs and the allowed median source energy is <10^{52} erg. A hypothetical population of transient sources has to be more common than 10^{-5} Mpc^{-3} yr^{-1} (5×10^{-8} Mpc^{-3} yr^{-1} for the E^{-2.13} spectrum) to account for the complete astrophysical neutrino flux.
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We present a measurement of the atmospheric neutrino oscillation parameters using three years of data from the IceCube Neutrino Observatory. The DeepCore infill array in the center of IceCube enables the detection and reconstruction of neutrinos produced by the interaction of cosmic rays in Earth's atmosphere at energies as low as â¼5 GeV. That energy threshold permits measurements of muon neutrino disappearance, over a range of baselines up to the diameter of the Earth, probing the same range of L/E_{ν} as long-baseline experiments but with substantially higher-energy neutrinos. This analysis uses neutrinos from the full sky with reconstructed energies from 5.6 to 56 GeV. We measure Δm_{32}^{2}=2.31_{-0.13}^{+0.11}×10^{-3} eV^{2} and sin^{2}θ_{23}=0.51_{-0.09}^{+0.07}, assuming normal neutrino mass ordering. These results are consistent with, and of similar precision to, those from accelerator- and reactor-based experiments.
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The quality of medical care delivered to patients with cancer near the end of life is a significant issue. Previous studies have defined several areas suggestive of aggressive cancer treatment as potentially representing poor quality care. The primary objective of current analysis was to examine chemotherapy and healthcare utilisation in the last 3 months of life among patients with cancer that received palliative chemotherapy. Patients were selected from the hospital administration database of the Diakonessenhuis Utrecht, the Netherlands. Data were extracted from the medical files. A total of 604 patients were included for analysis (median age: 64 years). For 300 patients (50%) chemotherapy was given in the last 3 months (CT+). For 76% (n = 229) of CT+ patients unplanned hospital admissions were made in these last 3 months, compared to 44% (n = 133) of CT- patients (p < .001). Visits to the emergency room in last 3 months were made by 67% (n = 202) of CT+ patients compared to 43% (n = 132) of CT- patients (p < .001). Healthcare consumption was significantly higher in patients who received chemotherapy in the last 3 months of life. Being able to inform our patients about these aspects of treatment can help to optimise both the quality of life and the quality of dying in patients with cancer.
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Antineoplásicos/uso terapéutico , Necesidades y Demandas de Servicios de Salud/estadística & datos numéricos , Neoplasias/tratamiento farmacológico , Cuidados Paliativos/métodos , Cuidado Terminal/estadística & datos numéricos , Adulto , Anciano , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Países BajosRESUMEN
BACKGROUND: Treating elderly colorectal cancer patients can be challenging. It is very important to carefully weigh the risks and benefits of potential treatments in individual patients. This treatment decision making can be guided by geriatric consultation. Our aim was to assess the effect of a geriatric evaluation on treatment decisions for older patients with colorectal cancer. METHODS: Colorectal cancer patients who were referred for a geriatric consultation between 2013 and 2015 in three Dutch teaching hospitals were included in a prospective database. The outcome of geriatric assessment, non-oncological interventions and geriatricians' treatment recommendations were evaluated. RESULTS: The total number of included referrals was 168. The median age was 81 years (range 60-94). Most patients (71%) had colon cancer and 49% had tumour stage III disease. The reason for geriatric consultation was uncertainty regarding the optimal oncologic treatment in 139 patients (83%). Overall 93% of patients suffered from geriatric impairments; non-oncological interventions that followed after geriatric consultation was mostly aimed at malnutrition. The geriatrician recommended the 'more intensive treatment' option in 69% and the 'less intensive treatment' option in 31% of which 63% 'supportive care only'. CONCLUSION: Geriatric consultation can be useful in treatment decision making in elderly patients with colorectal cancer. It may lead to changes in the treatment plan for individual cases and may result in an additional optimisation of patient's health status prior to treatment.
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Neoplasias Colorrectales , Evaluación Geriátrica/métodos , Medición de Riesgo/métodos , Anciano , Anciano de 80 o más Años , Toma de Decisiones Clínicas/métodos , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Femenino , Humanos , Masculino , Estadificación de Neoplasias , Países Bajos/epidemiología , Planificación de Atención al Paciente/organización & administración , Selección de Paciente , Derivación y Consulta , Ajuste de RiesgoRESUMEN
BACKGROUND: Ostomies are being placed in 35 % of patients after colorectal cancer surgery. As decision-making regarding colorectal surgery is challenging in the older patients, it is important to have insight in the potential impact due to ostomies. METHODS: An internet-based survey was sent to all members with registered email addresses of the Dutch Ostomy Patient Association. RESULTS: The response rate was 49 %; 932 cases were included of whom 526 were aged <70 years old ("younger respondents"), 301 were aged between 70 and 79 years old ("the elderly"), and 105 were aged ≥80 years old ("oldest old"). Ostomy-related limitations were similar in the different age groups, just as uncertainty (8-10 %) and dependency (18-22 %) due to the ostomy. A reduced quality of life was experienced least in the oldest old group (24 % vs 37 % of the elderly and 46 % of the younger respondents, p < 0.001). Over time, a decrease of limitations and impact due to the ostomy was observed. CONCLUSION: Older ostomates do not experience more limitations or psychosocial impact due to the ostomy compared to their younger counterparts. Over the years, impact becomes less distinct. Treatment decision-making is challenging in the older colorectal cancer patients but ostomy placement should not be withheld based on age alone.
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Neoplasias Colorrectales/cirugía , Estomía , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/psicología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Factores de TiempoRESUMEN
BACKGROUND: Quality of life (QoL) should be included in trials where treatment is expected to have a limited impact on long-term survival. We set out to determine whether phase III chemotherapy trials addressing solid malignancies with a poor prognosis include QoL as a study objective and to assess the extent to which these data have been published. METHODS: We performed a search of the National Institutes of Health clinical trial registry website to identify phase III chemotherapy trials for poor prognosis solid malignancies. The retrieved protocols were subsequently reviewed, to assess whether QoL was included as an outcome measure. Subsequently, a Medline, Embase and world-wide-web search was performed to identify any full text publication or conference abstract regarding the outcome of trials including QoL, which were then reviewed to determine whether and to what extend quality of life results were included. RESULTS: For the 201 included studies, we found that 57 % of trials did not include QoL as a study objective. Of the remaining trials, 50 % have not reported the QoL results in a full text publication, or presented these only as a single sentence statement. CONCLUSION: Evaluation and publication of QoL results of phase III chemotherapy trials for poor prognosis solid malignancies remains limited. This must be improved in order to provide patients suffering from these malignancies with adequate information regarding the benefits and risks of the treatment in terms of both prolongation and quality of life.
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Quimioterapia/métodos , Neoplasias/psicología , Humanos , Neoplasias/tratamiento farmacológico , Pronóstico , Calidad de Vida , Resultado del TratamientoRESUMEN
The purpose of this study was to determine possible differences in propulsion technique between propelling the wheelchair with and without a racket in the hand. Eight experienced wheelchair tennis players performed three submaximal exercise tests and six sprint tests on a wheelchair ergometer. Torque and velocity were measured during the tests and power output and timing variables were calculated. Differences between the conditions with and without racket were analyzed. When propelling with the racket, the racket side showed a significantly lower push time (P = 0.03), lower percentage push time (P = 0.001), shorter contact angle (P < 0.001), more power loss before (P = 0.006) and after (P = 0.001) the push, a higher peak (P = 0.009) and mean (P = 0.005) power output during the push, and a lower mean overall velocity (P = 0.03). When the same hand is compared when propelling with and without racket or when the sprint data were analyzed, similar significant differences were found. Propelling the wheelchair while holding a racket has negative effects on the propulsion technique and may lead to injuries of the upper extremity. The longer time needed to couple the hand with the racket to the rim leads to higher power losses and subsequently higher power output generation during the shorter push phase.
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Mano , Equipo Deportivo , Tenis , Silla de Ruedas , Adolescente , Adulto , Brazo , Fenómenos Biomecánicos , Estudios Transversales , Ergometría , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Torque , Adulto JovenRESUMEN
INTRODUCTION: Adequate decision-making in elderly colorectal cancer patients requires accurate information regarding risks of treatment. We analysed the outcome and survival of colorectal resections in the oldest old (≥85 years). METHODS: An analysis of the 2011-2012 data from two large nationwide registries: the Dutch Surgical Colorectal Audit (DSCA), containing all colorectal cancer resections, and the Netherlands Cancer Registry (NCR), containing survival data for all newly diagnosed malignancies. RESULTS: The study included more than 1200 patients aged ≥85 years (DSCA n = 1232, NCR n = 1206). The postoperative complication rate was 41 % in the oldest old. The frequency of cardiopulmonary complications rose rapidly with age, from 11 % in those <70 years to 38 % for the oldest old (p < 0.001). Postoperative 30-day mortality rate was 10 % in the oldest old. Three-month mortality was 14 % (compared with 3 % of patients <85 years; p < 0.001). One-year mortality was 24 % and 2-year mortality 36 %. After correction for expected mortality in the general population, excess mortality for the oldest old was 12 % in the first year and 3 % in the second year. CONCLUSIONS: In this study of more than 1200 colorectal cancer patients aged ≥85 years undergoing surgical resection, we found high rates of cardiopulmonary complications and excess mortality, particularly in the first year after surgery. We propose that these data could be incorporated into individualized treatment algorithms, which also include detailed information regarding the patients' health status.
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Colectomía/mortalidad , Neoplasias Colorrectales/mortalidad , Complicaciones Posoperatorias/mortalidad , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Pronóstico , Sistema de Registros , Tasa de Supervivencia , Factores de Tiempo , Adulto JovenRESUMEN
We report constraints on the sources of ultrahigh-energy cosmic rays (UHECRs) above 10^{9} GeV, based on an analysis of seven years of IceCube data. This analysis efficiently selects very high- energy neutrino-induced events which have deposited energies from 5×10^{5} GeV to above 10^{11} GeV. Two neutrino-induced events with an estimated deposited energy of (2.6±0.3)×10^{6} GeV, the highest neutrino energy observed so far, and (7.7±2.0)×10^{5} GeV were detected. The atmospheric background-only hypothesis of detecting these events is rejected at 3.6σ. The hypothesis that the observed events are of cosmogenic origin is also rejected at >99% CL because of the limited deposited energy and the nonobservation of events at higher energy, while their observation is consistent with an astrophysical origin. Our limits on cosmogenic neutrino fluxes disfavor the UHECR sources having a cosmological evolution stronger than the star formation rate, e.g., active galactic nuclei and γ-ray bursts, assuming proton-dominated UHECRs. Constraints on UHECR sources including mixed and heavy UHECR compositions are obtained for models of neutrino production within UHECR sources. Our limit disfavors a significant part of parameter space for active galactic nuclei and new-born pulsar models. These limits on the ultrahigh-energy neutrino flux models are the most stringent to date.
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The IceCube neutrino telescope at the South Pole has measured the atmospheric muon neutrino spectrum as a function of zenith angle and energy in the approximate 320 GeV to 20 TeV range, to search for the oscillation signatures of light sterile neutrinos. No evidence for anomalous ν_{µ} or ν[over ¯]_{µ} disappearance is observed in either of two independently developed analyses, each using one year of atmospheric neutrino data. New exclusion limits are placed on the parameter space of the 3+1 model, in which muon antineutrinos experience a strong Mikheyev-Smirnov-Wolfenstein-resonant oscillation. The exclusion limits extend to sin^{2}2θ_{24}≤0.02 at Δm^{2}â¼0.3 eV^{2} at the 90% confidence level. The allowed region from global analysis of appearance experiments, including LSND and MiniBooNE, is excluded at approximately the 99% confidence level for the global best-fit value of |U_{e4}|^{2}.
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Results from the IceCube Neutrino Observatory have recently provided compelling evidence for the existence of a high energy astrophysical neutrino flux utilizing a dominantly Southern Hemisphere data set consisting primarily of ν(e) and ν(τ) charged-current and neutral-current (cascade) neutrino interactions. In the analysis presented here, a data sample of approximately 35,000 muon neutrinos from the Northern sky is extracted from data taken during 659.5 days of live time recorded between May 2010 and May 2012. While this sample is composed primarily of neutrinos produced by cosmic ray interactions in Earth's atmosphere, the highest energy events are inconsistent with a hypothesis of solely terrestrial origin at 3.7σ significance. These neutrinos can, however, be explained by an astrophysical flux per neutrino flavor at a level of Φ(E(ν))=9.9(-3.4)(+3.9)×10(-19) GeV(-1) cm(-2) sr(-1) s(-1)(E(ν)/100 TeV(-2), consistent with IceCube's Southern-Hemisphere-dominated result. Additionally, a fit for an astrophysical flux with an arbitrary spectral index is performed. We find a spectral index of 2.2(-0.2)(+0.2), which is also in good agreement with the Southern Hemisphere result.
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A diffuse flux of astrophysical neutrinos above 100 TeV has been observed at the IceCube Neutrino Observatory. Here we extend this analysis to probe the astrophysical flux down to 35 TeV and analyze its flavor composition by classifying events as showers or tracks. Taking advantage of lower atmospheric backgrounds for showerlike events, we obtain a shower-biased sample containing 129 showers and 8 tracks collected in three years from 2010 to 2013. We demonstrate consistency with the (fe:fµ:fτ)â≈(1:1:1)â flavor ratio at Earth commonly expected from the averaged oscillations of neutrinos produced by pion decay in distant astrophysical sources. Limits are placed on nonstandard flavor compositions that cannot be produced by averaged neutrino oscillations but could arise in exotic physics scenarios. A maximally tracklike composition of (0:1:0)â is excluded at 3.3σ, and a purely showerlike composition of (1:0:0)â is excluded at 2.3σ.
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The differences in systemic T-cell responses between patients with psoriatic arthritis (PsA) and patients with cutaneous psoriasis (Ps) are still largely unknown. To determine differential features that could be used to distinguish PsA from Ps, we compared the cytokine secretion profile of circulating T cells in patients with PsA, patients with cutaneous Ps and control subjects. We determined Th1, Th2 and Th17 cytokine secretion of anti-CD3-stimulated peripheral blood mononuclear cells (PBMCs) using a cytokine bead array. Normality of data distribution was assessed by the Shapiro-Wilk test, and statistical significance was calculated by the Mann-Whitney test. Phenotypic characterization of circulating T cells was performed by fluorescence-activated cell sorting analysis. We found that the major systemic differences distinguishing PsA from cutaneous Ps were the increased secretion of interleukin (IL)-2 by α-CD3-stimulated PBMCs and a higher percentage of circulating CD3+ T cells expressing the proliferation marker CD71 in PsA. These results indicate IL-2 as a possible biomarker of PsA, and suggest a role of circulating T cells with high proliferative capacity in the pathogenesis of PsA.
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Artritis Psoriásica/metabolismo , Complejo CD3/inmunología , Interleucina-2/metabolismo , Leucocitos Mononucleares/metabolismo , Psoriasis/metabolismo , Adolescente , Adulto , Citocinas/metabolismo , Femenino , Citometría de Flujo , Humanos , Leucocitos Mononucleares/inmunología , Masculino , Persona de Mediana Edad , Linfocitos T Colaboradores-Inductores/metabolismo , Adulto JovenRESUMEN
The vast majority of patients with fragile X syndrome show a folate-sensitive fragile site at Xq27.3 (FRAXA) at the cytogenetic level, and both amplification of the (CGG)n repeat and hypermethylation of the CpG island in the 5' fragile X gene (FMR-1) at the molecular level. We have studied the FMR-1 gene of a patient with the fragile X phenotype but without cytogenetic expression of FRAXA, a (CGG)n repeat of normal length and an unmethylated CpG island. We find a single point mutation in FMR-1 resulting in an lle367Asn substitution. This de novo mutation is absent in the patient's family and in 130 control X chromosomes, suggesting that the mutation causes the clinical abnormalities. Our results suggest that mutations in FMR-1 are directly responsible for fragile X syndrome, irrespective of possible secondary effects caused by FRAXA.