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Social memory dysfunction is an especially devastating symptom of many neuropsychiatric disorders, which makes understanding the cellular and molecular processes that contribute to such abnormalities important. Evidence suggests that the hippocampus, particularly the CA2 region, plays an important role in social memory. We sought to identify potential mechanisms of social memory dysfunction in the hippocampus by investigating features of neurons, glia, and the extracellular matrix (ECM) of BTBR mice, an inbred mouse strain with deficient social memory. The CA2 is known to receive inputs from dentate gyrus adult-born granule cells (abGCs), neurons known to participate in social memory, so we examined this cell population and found fewer abGCs, as well as fewer axons from abGCs in the CA2 of BTBR mice compared to controls. We also found that BTBR mice had fewer pyramidal cell dendritic spines, in addition to fewer microglia and astrocytes, in the CA2 compared to controls. Along with diminished neuronal and glial elements, we found atypical perineuronal nets (PNNs), specialized ECM structures that regulate plasticity, in the CA2 of BTBR mice. By diminishing PNNs in the CA2 of BTBR mice to control levels, we observed a partial restoration of social memory. Our findings suggest that the CA2 region of BTBR mice exhibits multiple cellular and extracellular abnormalities and identify atypical PNNs as one mechanism producing social memory dysfunction, although the contribution of reduced abGC afferents, pyramidal cell dendritic spine, and glial cell numbers remains unexplored.

Serious mental illness (SMI) is a major source of suffering among Medicare beneficiaries. To date, limited evidence exists evaluating whether Medicare accountable care organizations (ACOs) are associated with decreased spending among people with SMI. Using national Medicare data from the period 2009-17, we performed difference-in-differences analyses evaluating changes in spending and use associated with enrollment in the Medicare Shared Savings Program (MSSP) among beneficiaries with SMI. After five years, participation in MSSP ACOs was associated with small savings for beneficiaries with SMI (-$233 per person per year) in total health care spending, primarily related to savings from chronic medical conditions (excluding mental health; -$227 per person per year) and not from savings related to mental health services (-$6 per person per year). Savings were driven by reductions in acute and postacute care for medical conditions. Further work is needed to ensure that Medicare ACOs invest in strategies to reduce potentially unnecessary care related to mental health disorders and to improve health outcomes.

Medications for opioid use disorder (MOUD) remain highly inaccessible despite demonstrated effectiveness. We examine the extent of screening for opioid use and availability of MOUD in a national cross-section of multi-physician primary care and multispecialty practices. Drawing on an existing framework to characterize the internal and environmental context, we assess socio-technical, organizational-managerial, market-based, and state-regulation factors associated with the use of opioid screening and offering of MOUD in a practice. A total of 26.2% of practices offered MOUD, while 69.4% of practices screened for opioid use. Having advanced health information technology functionality was positively associated with both screening for opioid use and offering MOUD in a practice, while access to on-site behavioral clinicians was positively associated with offering MOUD in adjusted models. These results suggest that improving access to information and expertise may enable physician practices to respond more effectively to the nation’s ongoing opioid epidemic.

Experience governs neurogenesis from radial-glial neural stem cells (RGLs) in the adult hippocampus to support memory. Transcription factors in RGLs integrate physiological signals to dictate self-renewal division mode. Whereas asymmetric RGL divisions drive neurogenesis during favorable conditions, symmetric divisions prevent premature neurogenesis while amplifying RGLs to anticipate future neurogenic demands. The identities of transcription factors regulating RGL symmetric self-renewal, unlike those that regulate RGL asymmetric self-renewal, are not known. Here, we show that the transcription factor Kruppel-like factor 9 (Klf9) is elevated in quiescent RGLs and inducible, deletion of Klf9 promotes RGL activation state. Clonal analysis and longitudinal intravital 2-photon imaging directly demonstrate that Klf9 functions as a brake on RGL symmetric self-renewal. In vivo translational profiling of RGLs lacking Klf9 generated a blueprint of RGL symmetric self-renewal for stem cell community. Together, these observations identify Klf9 as a transcriptional regulator of neural stem cell expansion in the adult hippocampus.

In a population of 302, 000, in a Midlands district of England, the estimated prevalence of idiopathic Parkinson's disease (IPD) increased from 108 to 121 per 100, 000 from 1982 to 1992. Individual general practice prevalence ranged quite widely. Webster ratings were significantly more often scored in 1992, but at a lower level of severity, suggesting earlier diagnosis. Incidence in 1992 was estimated as 12 per 100, 000 per annum. Micrographia, when copying interlocking pentagons, was significantly related to Hoehn & Yahr scores. Over the 10-year period, there has been a considerable change in prescribing: a positive response to medication was confirmed as a good diagnostic indicator. Progression of symptoms and an increase of physical disability was noted in those of the 1982 study alive in 1992.

Background Although there is abundant evidence that moderate and high doses of radiation can cause leukaemia and other cancers, there is little direct evidence on the leukaemogenic (or other carcin...

We conducted a large record-based case-control study testing associations between childhood cancer and natural background radiation. Cases (27,447) born and diagnosed in Great Britain during 1980-2006 and matched cancer-free controls (36,793) were from the National Registry of Childhood Tumours. Radiation exposures were estimated for mother's residence at the child's birth from national databases, using the County District mean for gamma rays, and a predictive map based on domestic measurements grouped by geological boundaries for radon. There was 12% excess relative risk (ERR) (95% CI 3, 22; two-sided P=0.01) of childhood leukaemia per millisievert of cumulative red bone marrow dose from gamma radiation; the analogous association for radon was not significant, ERR 3% (95% CI -4, 11; P=0.35). Associations for other childhood cancers were not significant for either exposure. Excess risk was insensitive to adjustment for measures of socio-economic status. The statistically significant leukaemia risk reported in this reasonably powered study (power ~50%) is consistent with high-dose rate predictions. Substantial bias is unlikely, and we cannot identify mechanisms by which confounding might plausibly account for the association, which we regard as likely to be causal. The study supports the extrapolation of high-dose rate risk models to protracted exposures at natural background exposure levels.

The magnitude of the risks from low doses of radiation is one of the central questions in radiological protection. It is particularly relevant when discussing the justification and optimization of diagnostic medical exposures. Medical X-rays can undoubtedly confer substantial benefits in the healthcare of patients, but not without exposing them to effective doses ranging from a few microsieverts to a few tens of millisieverts. Do we have any evidence that these levels of exposure result in significant health risks to patients? The current consensus held by national and international radiological protection organizations is that, for these comparatively low doses, the most appropriate risk model is one in which the risk of radiation-induced cancer and hereditary disease is assumed to increase linearly with increasing radiation dose, with no threshold (the so-called linear no threshold (LNT) model). However, the LNT hypothesis has been challenged both by those who believe that low doses of radiation are more damaging than the hypothesis predicts and by those who believe that they are less harmful, and possibly even beneficial (often referred to as hormesis). This article reviews the evidence for and against both the LNT hypothesis and hormesis, and explains why the general scientific consensus is currently in favour of the LNT model as the most appropriate dose-response relationship for radiation protection purposes at low doses. Finally, the impact of the LNT model on the assessment of the risks from medical X-rays and how this affects the justification and optimization of such exposures is discussed.

Leon Trotsky [1] recognized the power of terrorism whenhe stated that ‘War, like revolution is founded uponintimidation. A victorious war, generally speaking,destroys only an insignificant part of the conquered army,intimidating the remainder and breaking their will . . .Terror . . . kills individuals, and intimidates thousands.’It has been previously argued that ‘weapons of massdestruction’, now more accurately known as ‘weapons ofmass effect’, would never be used by terrorists becausethey would have nothing to gain by inflicting casualties ona large scale. Events of recent years have led towidespread re-evaluation of emergency preparednessarrangements by the USA, the North Atlantic TreatyOrganization alliance and the European Union. The UKhas a history of dealing with the consequences ofconventional terrorism and has well-developed systems inplace for detecting and dealing with chemical and nuclearaccidents and communicable disease outbreaks.This wasenhanced by comprehensive guidance and training onplanning for major incidents and many individuals andinstitutions with an international reputation in nuclearbiological and chemical defence [2–4].This article considers examples of chemical,biological,radiological and nuclear terrorism,the agents that may be

The timeliness and adequacy of inpatient discharge communication between hospitals and general practitioners (GPs) in Northamptonshire was examined by a postal questionnaire survey of GPs of patients recently discharged from hospital, with the aim of improving the co-ordination of discharge procedures, and hence improving continuity of care. The questionnaire measured when and how the GP was informed of the discharge, and examined the adequacy of medical, therapeutic and social details in the discharge documents sent out by the hospital. It was found that 67 per cent of discharges had been notified to the GP by the hospital within five days of discharge. With notable exceptions the discharge documents were considered timely. General practitioners were less satisfied with the adequacy of discharge communication in terms of 'social' topics such as transport needs, social services back-up, and whether a patient with a malignancy knew about his or her diagnosis. The GPs of patients under geriatricians were more satisfied with the quality of discharge documents. Comparison with an earlier study suggested that the speed of communication and involvement of GPs in discharge in Northamptonshire is not as satisfactory as that found in Oxford in 1986. It was concluded that within the county there appear to be models of good practice in terms of discharge communication with GPs. These standards should be adopted by other specialties to match or improve on existing good practice.

The timeliness and adequacy of inpatient discharge communication between hospitals and general practitioners (GPs) in Northamptonshire was examined by a postal questionnaire survey of GPs of patients recently discharged from hospital, with the aim of improving the co-ordination of discharge procedures, and hence improving continuity of care. The questionnaire measured when and how the GP was informed of the discharge, and examined the adequacy of medical, therapeutic and social details in the discharge documents sent out by the hospital. It was found that 67 per cent of discharges had been notified to the GP by the hospital within five days of discharge. With notable exceptions the discharge documents were considered timely. General practitioners were less satisfied with the adequacy of discharge communication in terms of 'social' topics such as transport needs, social services back-up, and whether a patient with a malignancy knew about his or her diagnosis. The GPs of patients under geriatricians were more satisfied with the quality of discharge documents. Comparison with an earlier study suggested that the speed of communication and involvement of GPs in discharge in Northamptonshire is not as satisfactory as that found in Oxford in 1986. It was concluded that within the county there appear to be models of good practice in terms of discharge communication with GPs. These standards should be adopted by other specialties to match or improve on existing good practice.

People living in 102 rural households on private water supplies, and their matched controls on mains water, were asked about their health in a postal questionnaire. People using private water supplies were more likely to be from farming families (and so in socioeconomic class II) and less likely to be retired than their controls on mains water. Families using contaminated private supplies ('dirty' water) reported lower rates of colds and respiratory illnesses than people using mains water or uncontaminated private supplies ('clean' water). The mains-water users had visited their general practitioners more often in the last three months. There was no difference in the incidence of acute abdominal symptoms recorded in a diary kept by survey participants. Considering children, who are more susceptible to infectious illnesses, the only difference in health was that children in the families with 'dirty' private water took more medication (though reported illness less often) than others. In conclusion, the study indicated that private water is not harmful to health, but the results must be put in the context of evidence from other work.

BACKGROUND AND PURPOSE: To test the design and feasibility of a very large randomised controlled trial assessing the efficacy and safety of antithrombotic therapy started within 48 hours of symptom onset in patients with suspected acute ischaemic stroke. DESIGN: Randomised controlled multicentre open study, with a 3 x 2 factorial design, allocating patients to: medium dose subcutaneous heparin (12,500 units twice per day), versus low dose subcutaneous heparin (5000 units twice per day) versus no heparin; and aspirin (300 mg daily) versus no aspirin. Treatment was given for two weeks or until discharge from hospital if sooner. RESULTS: 984 patients were randomised. CT was performed in 924 (94%) (before randomisation in 622/984 (63%). Within 14 days: 97 patients had died (10%), 30 (3.0%) had a fatal or non-fatal recurrent ischaemic stroke, nine (0.9%) had fatal or non-fatal recurrent stroke due to intracranial haemorrhage, and eight (0.8%) had a fatal or non-fatal pulmonary embolus. At six months, vital status was known for 975 patients (99%), of whom 210 (22%) were dead, 373 (38%) were alive but dependent, and 225 (23%) were independent but not fully recovered. CONCLUSIONS: The trial procedures proved practicable and a wide variety of patients were recruited. Sample size calculation based on the event rates confirmed that reliable evidence on the balance of risk and benefit of early antithrombotic therapy might require a study with more than 20,000 patients. Recruitment rates in the pilot study indicated that if about 200 hospitals participated, recruitment could be completed by 1997.