Evidence for neutrino emission from the nearby active galaxy NGC 1068.

A supermassive black hole, obscured by cosmic dust, powers the nearby active galaxy NGC 1068. Neutrinos, which rarely interact with matter, could provide information on the galaxy's active core. We searched for neutrino emission from astrophysical objects using data recorded with the IceCube neutrino detector between 2011 and 2020. The positions of 110 known gamma-ray sources were individually searched for neutrino detections above atmospheric and cosmic backgrounds. We found that NGC 1068 has an excess of [Formula: see text] neutrinos at tera-electron volt energies, with a global significance of 4.2σ, which we interpret as associated with the active galaxy. The flux of high-energy neutrinos that we measured from NGC 1068 is more than an order of magnitude higher than the upper limit on emissions of tera-electron volt gamma rays from this source.

Strong Constraints on Neutrino Nonstandard Interactions from TeV-Scale ν_{µ} Disappearance at IceCube.

We report a search for nonstandard neutrino interactions (NSI) using eight years of TeV-scale atmospheric muon neutrino data from the IceCube Neutrino Observatory. By reconstructing incident energies and zenith angles for atmospheric neutrino events, this analysis presents unified confidence intervals for the NSI parameter ε_{µτ}. The best-fit value is consistent with no NSI at a p value of 25.2%. With a 90% confidence interval of -0.0041≤ε_{µτ}≤0.0031 along the real axis and similar strength in the complex plane, this result is the strongest constraint on any NSI parameter from any oscillation channel to date.

Search for Relativistic Magnetic Monopoles with Eight Years of IceCube Data.

We present an all-sky 90% confidence level upper limit on the cosmic flux of relativistic magnetic monopoles using 2886 days of IceCube data. The analysis was optimized for monopole speeds between 0.750c and 0.995c, without any explicit restriction on the monopole mass. We constrain the flux of relativistic cosmic magnetic monopoles to a level below 2.0×10^{-19} cm^{-2} s^{-1} sr^{-1} over the majority of the targeted speed range. This result constitutes the most strict upper limit to date for magnetic monopoles with ß≳0.8 and up to ß∼0.995 and fills the gap between existing limits on the cosmic flux of nonrelativistic and ultrarelativistic magnetic monopoles.

Digitizing Medicines for Remote Capture of Oral Medication Adherence Using Co-encapsulation.

High-resolution measurement of medication adherence is essential to personalized drug therapy. A US Food and Drug Administration (FDA)-cleared device, using an edible ingestion sensor (IS), external wearable patch, and paired mobile device can detect and record ingestion events. Oral medications must be combined with an IS to generate precise "digitized-medication" ingestion records. We developed a Good Manufacturing Practice protocol to repackage oral medications with the IS within certified Capsugel capsules, termed co-encapsulation (CoE). A randomized bioequivalence study of CoE-IS-Rifamate (Isoniazid/Rifampin 150/300 mg) vs. native-Rifamate was conducted in 12 patients with active Mycobacterium tuberculosis and demonstrated bioequivalence using the population method ratio test (95% confidence interval). Subsequently, CoE-IS-medications across all biopharmaceutical classes underwent in vitro dissolution testing utilizing USP and FDA guidelines. CoE-IS medications tested met USP dissolution specifications and were equivalent to their native formulations. CoE combines oral medications with the IS without altering the quality of the native formulation, generating "digitized" medications for remote capture of dosing histories.

Simple, illustrated medicines information improves ARV knowledge and patient self-efficacy in limited literacy South African HIV patients.

Few studies have investigated antiretroviral (ARV) knowledge and self-efficacy in limited literacy patients. Using a randomized controlled study design, we investigated the influence of a simple pre-tested patient information leaflet (PIL) containing both text and illustrations on HIV- and ARV-related knowledge and on self-efficacy over six months in a limited literacy African population. The recruited patients were randomly allocated to either control (standard care) or intervention group (standard care plus illustrated PIL). HIV and medicines-related knowledge was evaluated with a 22-question test at baseline, one, three, and six months. Self-efficacy was assessed using a modified version of the HIV Treatment Adherence Self-Efficacy Scale. Two-thirds of the patients were female, mean age was 39.0 ± 9.6 years and mean education was 7.3 ± 2.8 years. Patients who received the PIL showed a significant knowledge increase over the six-month period (62.0-94.4%), with improvement at each subsequent interview whereas the control group showed no improvement. At baseline, side effect knowledge was the lowest (50-56%) but increased in the intervention group to 92%. Similarly, other medicine-related knowledge at baseline (57-67%) improved significantly (93%) and was sustained over six months. Cohen's d values post-baseline ranged between 1.36 and 2.18, indicating a large intervention effect. Self-efficacy improved significantly over six months in intervention but not control patients. At baseline, patients with ≤ 3 years of education had lower knowledge and self-efficacy but this was not observed post-intervention, which we attribute to the PIL mitigating the effect of limited education. Knowledge and self-efficacy were significantly correlated in the intervention group. In conclusion, a low-cost intervention of a well-designed, pre-tested, simple, illustrated PIL significantly increased both ARV knowledge and self-efficacy in HIV patients with limited education.

Multi-modal delivery of therapeutics using biomaterial scaffolds.

Functionalisation of biomaterials with therapeutic moieties (proteins, drugs, genes) is a pre-requisite to tissue regeneration and restoration of function following injury or disease. However, up until now, single-factor delivery has not proven to be clinically efficacious, most likely due to the complex nature of pathological states. In this regard, strategies that respect the complex nature of disease can prove successful, paving the way for the delivery of several factors to modulate several stages of the pathology over time. Biomaterials offer opportunities to deliver multiple therapeutics in a temporal manner (multi-modal release) using a number of strategies. The importance of these strategies will be described, as well as the methodologies used to achieve multi-modal release. Furthermore, strategies to engineer more programmed and responsive biomaterials as multi-modal delivery systems will be explored.

The relationship between insight and neurological dysfunction in first-episode psychosis.

PURPOSE: Impaired insight is commonly seen in psychosis and some studies have proposed that is a biologically based deficit. Support for this view comes from the excess of neurological soft signs (NSS) observed in patients with psychoses and their neural correlates which demonstrate a degree of overlap with the regions of interest implicated in neuroimaging studies of insight. The aim was to examine the relationship between NSS and insight in a sample of 241 first-episode psychosis patients. METHOD: Total scores and subscale scores from three insight measures and two NSS scales were correlated in addition to factors representing overall insight and NSS which we created using principal component analysis. RESULTS: There were only four significant associations when we controlled for symptoms. "Softer" condensed neurological evaluation (CNE) signs were associated with our overall insight factor (r = 0.19, P = 0.02), with total Birchwood (r = -0.24, P < 0.01), and the Birchwood subscales; recognition of mental illness (r = -0.24, P < 0.01) and need for treatment (r = -0.18, P = 0.02). Total neurological evaluation scale (NES) and recognition of the achieved effects of medication were also weakly correlated (r = 0.14, P = 0.04). CONCLUSION: This study does not support a direct link between neurological dysfunction and insight in psychosis. Our understanding of insight as a concept remains in its infancy.

Systematic review: kidney transplantation compared with dialysis in clinically relevant outcomes.

Individual studies indicate that kidney transplantation is associated with lower mortality and improved quality of life compared with chronic dialysis treatment. We did a systematic review to summarize the benefits of transplantation, aiming to identify characteristics associated with especially large or small relative benefit. Results were not pooled because of expected diversity inherent to observational studies. Risk of bias was assessed using the Downs and Black checklist and items related to time-to-event analysis techniques. MEDLINE and EMBASE were searched up to February 2010. Cohort studies comparing adult chronic dialysis patients with kidney transplantation recipients for clinical outcomes were selected. We identified 110 eligible studies with a total of 1 922 300 participants. Most studies found significantly lower mortality associated with transplantation, and the relative magnitude of the benefit seemed to increase over time (p < 0.001). Most studies also found that the risk of cardiovascular events was significantly reduced among transplant recipients. Quality of life was significantly and substantially better among transplant recipients. Despite increases in the age and comorbidity of contemporary transplant recipients, the relative benefits of transplantation seem to be increasing over time. These findings validate current attempts to increase the number of people worldwide that benefit from kidney transplantation.

[Medical students as members of the health care team]. / Los estudiantes de medicina como parte del equipo de salud.

BACKGROUND: Teaching hospitals include both undergraduate and postgraduate students, but the role of medical students in the health care team has not been clearly established. AIM: To know the opinion of different professionals about the role of medical students and how this opinion may have an influence in medical education. MATERIAL AND METHODS: A qualitative method was used, asking open questions to focus groups of physicians, nurses and midwives, technicians and undergraduate medical students of 4th and 5th grade. RESULTS: Physicians believe that medical students have no special role in the health care team, nurses think that they may help in communication with patients, and technicians (nurses's aids) value their companionship and closeness with patients. Medical students recognize that their main function is to learn but they are aware that they do help patients. They suggest increasing their integration with other students of other health related careers. CONCLUSIONS: Although medical students are usually not seen as part of the health care team, they may fulfill a role with patients during their clinical learning practice. This would improve the quality of their training and the multidisciplinary work of the health care team.

The impact of pancreas transplantation on kidney allograft survival.

Whether pancreas after kidney transplantation (PAK) compromises kidney allograft survival, and what pre-PAK glomerular filtration rate (GFR) should be used to select patients for PAK is unclear. We analyzed all (n = 2776) PAK recipients in the United States between 1989 and 2007 and compared their risk of kidney failure to a comparator group of n = 13 635 young adult diabetic kidney only transplant recipients during the same time after accounting for selection bias by the use of a propensity score for PAK in a multivariate time to event analysis. In a secondary analysis, we determined the association of pre-PAK GFR with subsequent kidney allograft survival. Despite an increased risk of death early after pancreas transplantation, PAK recipients had a decreased long-term risk of kidney allograft failure compared to diabetic kidney only transplant recipients HR = 0.89; 95% CI: [0.78-1.00]; p = 0.05. An association of pre-PAK GFR with kidney survival was not evident until 3 years after pancreas transplantation, and patients with a pre-PAK GFR of 30-39 mL/min still attained 10-year post-PAK kidney survival of 69%. We conclude that PAK is associated with improved kidney allograft survival, and pre-PAK GFR 30-39 mL/min should not preclude PAK. Expanded use of PAK is warranted.

Modifiable and fixed factors predicting quality of life in people with colorectal cancer.

BACKGROUND: People with colorectal cancer have impaired quality of life (QoL). We investigated what factors were most highly associated with it. METHODS: Four hundred and ninety-six people with colorectal cancer completed questionnaires about QoL, functioning, symptoms, co-morbidity, cognitions and personal and social factors. Disease, treatment and co-morbidity data were abstracted from case notes. Multiple linear regression identified modifiable and unmodifiable factors independently predictive of global quality of life (EORTC-QLQ-C30). RESULTS: Of unmodifiable factors, female sex (P<0.001), more self-reported co-morbidities (P=0.006) and metastases at diagnosis (P=0.036) significantly predicted poorer QoL, but explained little of the variability in the model (R(2)=0.064). Adding modifiable factors, poorer role (P<0.001) and social functioning (P=0.003), fatigue (P=0.001), dyspnoea (P=0.001), anorexia (P<0.001), depression (P<0.001) and worse perceived consequences (P=0.013) improved the model fit considerably (R(2)=0.574). Omitting functioning subscales resulted in recent diagnosis (P=0.002), lower perceived personal control (P=0.020) and travel difficulties (P<0.001) becoming significant predictors. CONCLUSION: Most factors affecting QoL are modifiable, especially symptoms (fatigue, anorexia, dyspnoea) and depression. Beliefs about illness are also important. Unmodifiable factors, including metastatic (or unstaged) disease at diagnosis, have less impact. There appears to be potential for interventions to improve QoL in patients with colorectal cancer.

Los estudiantes de medicina como parte del equipo de salud / Medical students as members of the health care team

Background: Teaching hospitals include both undergraduate and postgraduate students, but the role of medical students in the health care team has not been clearly established. Aim: To know the opinion of different professionals about the role of medical students and how this opinion may have an influence in medical education. Material and Methods: A qualitative method was used, asking open questions to focus groups of physicians, nurses and midwives, technicians and undergraduate medical students of 4th and 5th grade. Results: Physicians believe that medical students have no special role in the health care team, nurses think that they may help in commu-nication with patients, and technicians (nurses’s aids) value their companionship and closeness with patients. Medical students recognize that their main function is to learn but they are aware that they do help patients. They suggest increasing their integration with other students of other health related careers. Conclusions: Although medical students are usually not seen as part of the health care team, they may fulfll a role with patients during their clinical learning practice. This would improve the quality of their training and the multidisciplinary work of the health care team.

Anti-interferon-γ autoantibody and opportunistic infections: case series and review of the literature.

Immune defects in interleukin-12-dependent interferon-gamma (IFN-γ) pathways are associated with disseminated infections caused by non-tuberculous mycobacteria (NTM) and Salmonella. Recently, there have been an increasing number of reports of acquired autoantibodies to IFN-γ in adults, especially in Asian patients. We describe here three human immunodeficiency virus-negative Thai adults who had persistent or recurrent disseminated infections caused by NTM, Salmonella, and other opportunistic pathogens, possibly due to anti-IFN-γ autoantibodies. The antibodies were shown to exhibit very high inhibitory activity to IFN-γ. Two patients also developed Sweet's syndrome during the course of infections. In addition, we also review all previous reports of patients with anti-IFN-γ antibodies who were susceptible to NTM and Salmonella infections.

Post-traumatic amnesia and its relationship to the functional outcome of people with severe traumatic brain injury.

OBJECTIVE: To investigate the relationship between Post-Traumatic Amnesia (PTA) duration, length of stay and functional outcomes in Australian in-patients with severe traumatic brain injury (TBI). DESIGN: Retrospective, descriptive study using prospectively collected data from the Uniform Data Set for Medical Rehabilitation (UDSMR). METHODS: Prospective collection of Westmead PTA scores and analysis of database for admissions for primary TBI rehabilitation from 1993-2003. Functional Independence Measure (FIM) was used to measure functional outcome. Statistical analysis using SPSS Version 13. RESULTS: Six hundred and thirty-eight consecutive admissions; 611 patients had PTA classified by ranges, 436 of whom had an exact number of PTA days. Mean age 37.6 years; more than 90% had a PTA duration greater than 1 week. Significant predictors of discharge FIM scores and total length of hospitalization were PTA duration, admission FIM scores and acute length of hospitalization. CONCLUSIONS: PTA duration correlates with length of hospitalization and discharge function. PTA duration affects recovery rate. Implications include use of PTA duration for prognosticating, discharge planning and funding systems.

Predictors of outcome in first-episode schizophrenia over the first 4 years of illness.

BACKGROUND: The outcome of schizophrenia appears to be more favourable than once thought. However, methodological issues, including the reliance on diagnosis at first presentation have limited the validity of outcome studies to date. METHOD: We conducted a first-episode follow-up study of 97 patients with DSM-IV schizophrenia over the first 4 years of illness. First presentation and follow-up assessments were compared using paired t tests and a forced-entry regression analysis was used to determine prognostic variables. RESULTS: There were significant improvements in positive and negative symptoms and global assessment of functioning between first presentation and follow-up. At first presentation, fewer negative symptoms (t=-3.40, p<0.01), more years spent in education (t=3.25, p<0.01), and a shorter duration of untreated psychosis (DUP) (t=-2.77, p<0.01) significantly predicted a better outcome at follow-up. CONCLUSIONS: The outcome of schizophrenia may not be as pessimistic as once thought and most patients did not display a downward deteriorating course of illness. This study supports the relationship between DUP and outcome beyond the early stages of illness.

A prospective evaluation of adherence to medication in first episode schizophrenia.

The aim of this study was to identify the features of first episode schizophrenia that predict adherence antipsychotic medication at six-month follow-up. We used validated instruments to assess clinical and socio-demographic variables in all patients with first episode schizophrenia from a defined geographical area admitted to a Dublin psychiatric hospital over a four-year period (N=100). At six-month follow-up (N=60) we assessed adherence to medication using the Compliance Interview. One third of patients with schizophrenia were non-adherent with medication within six months of their first episode of illness. High levels of positive symptoms at baseline, lack of insight at baseline, alcohol misuse at baseline and previous drug misuse predict non-adherence. These results indicate that an identifiable subgroup of patients with first episode schizophrenia is at high risk of early non-adherence to medication. While high positive symptom scores pre-date and predict non-adherence in most patients, reduced insight is the best predictor of non-adherence in patients who do not misuse alcohol or other drugs.

Early insight predicts depression and attempted suicide after 4 years in first-episode schizophrenia and schizophreniform disorder.

OBJECTIVE: To map the development of insight in the 4 years after presentation with first-episode schizophrenia and schizophreniform disorder and to determine the effects of evolving insight on depression and the likelihood of attempted suicide. METHOD: We assessed 101 individuals at presentation, 6 months and 4 years. We measured insight, including recognition of mental illness, recognition of need for treatment and ability to relabel psychotic symptoms. We measured depression and recorded all suicide attempts. RESULTS: Insight improved with time. Recognition of mental illness at 6 months predicted depression and attempted suicide at 4 years. CONCLUSION: Six months after presentation, the greater the acknowledgement by people that they had a mental illness, the more depressed they were at 4 years and the greater the likelihood that they would attempt suicide by 4 years. This may have implications for disclosure of diagnosis.