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Two sentiments governed the postwar world: fear and hope. These two feelings dominated the debates that gave birth to both the Charter of the United Nations and the Universal Declaration of Human Rights. The League of Nations had failed. Leaders had expressed the desire for a world grounded in human rights but could not agree on what that meant or whether individual rights trumped the sovereign rights of nations. The UN Charter reflected these concerns, recognizing human rights but leaving their scope undefined. No precedents existed to guide the work. A committee of eighteen nations, chaired by Eleanor Roosevelt, accepted the unprecedented assignment of defining basic rights for all people everywhere. After consulting with noted jurists, philosophers, and social justice organizations, the committee set out to draft a document that would recognize the horrors of war and engender a commitment to peace. They envisioned a world governed more by hope than by fear. It was hard work. The debate was punctuated by escalating Cold War politics. A legally binding document seemed out of reach. All efforts turned instead to securing a declaration of human rights, which ultimately paved the way for legally binding commitments and energized a budding human rights movement.
Rodent models of schizophrenia (SCZ) are indispensable when screening for novel treatments, but quantifying their translational relevance with the underlying human pathophysiology has proved difficult. A novel systems methodology (shown in Figure 1) was developed integrating and comparing proteomic data of anterior prefrontal cortex tissue from SCZ post-mortem brains and matched controls with data obtained from four established glutamatergic rodent models, with the aim of evaluating which of these models represent SCZ most closely. Liquid chromatography coupled tandem mass spectrometry (LC-MSE) proteomic profiling was applied comparing healthy and “disease state” in human post-mortem samples and rodent brain tissue samples. Protein-protein interaction networks were constructed from significant abundance changes and enrichment analyses enabled the identification of pathophysiological characteristics of the disorder, which were represented across all four rodent models. Subsequently, these functional domains were used for cross-species comparisons. Five functional domains such as “development and differentiation” represented across all four rodent models, were identified. It was quantified that the chronic phencyclidine (cPCP) model represented SCZ brain changes most closely for four of these functional domains, by using machine-learning techniques. This is the first study aiming to quantify which rodent model recapitulates the neuropathological features of SCZ most closely. The methodology and findings presented here support recent efforts to overcome translational hurdles of preclinical psychiatric research by associating behavioural endophenotypes with distinct biological processes.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Health anxiety is an under-recognised but a frequent cause of distress. It is particularly common in general hospitals.
We carried out an 8-year follow-up of medical out-patients with health anxiety (hypochondriasis) enrolled in a randomised-controlled trial in five general hospitals in London, Middlesex and Nottinghamshire. Randomisation was to a mean of six sessions of cognitive behaviour therapy adapted for health anxiety (CBT-HA) or to standard care in the clinics. The primary outcome was a change in score on the Short Health Anxiety Inventory, with generalised anxiety and depression as secondary outcomes. Of 444 patients aged 16–75 years seen in cardiology, endocrinology, gastroenterology, neurology and respiratory medicine clinics, 306 (68.9%) were followed-up 8 years after randomisation, including 36 who had died. The study is registered with controlled-trials.com, ISRCTN14565822.
There was a significant difference in the HAI score in favour of CBT-HA over standard care after 8 years [1.83, 95% confidence interval (CI) 0.25–3.40, p = 0.023], between group differences in generalised anxiety were less (0.54, 95% CI −0.29 to 1.36), p = 0.20, ns), but those for depression were greater at 8 years (1.22, 95% CI 0.42–2.01, p < 0.003) in CBT-HA than in standard care, most in standard care satisfying the criteria for clinical depression. Those seen by nurse therapists and in cardiology and gastrointestinal clinics achieved the greatest gains with CBT-HA, with greater improvement in both symptoms and social function.
CBT-HA is a highly long-term effective treatment for pathological health anxiety with long-term benefits. Standard care for health anxiety in medical clinics promotes depression. Nurse therapists are effective practitioners.
Neutrophil–lymphocyte ratio has been associated with clinical outcomes in several groups of cardiac patients, including patients with coronary artery disease, cardiac failure, and cardiac transplant recipients. We hypothesised that pre- and/or post-operative haematological cell counts are associated with clinical outcomes in children undergoing cardiac surgery for CHD. We performed a post hoc analysis of data collected as part of a prospective observational cohort study (n = 83, data available n = 47) of children evaluated for glucocorticoid receptor levels after cardiac surgery (July 2015–January 2016). The association of neutrophil–lymphocyte ratio with low cardiac output syndrome, time to inotrope free, and vasoactive-inotropic score was examined using proportional odds analysis, cox regression, and linear regression models, respectively. A majority (80%) of patients were infants (median/interquartile range 4.1/0.2–7.6 months) with conotruncal (36%) and left-sided obstructed lesions (28%). Two patients required mechanical circulatory support and three died. Higher pre-operative neutrophil–lymphocyte ratio was associated with higher cumulative odds of severe/moderate versus mild low cardiac output on post-operative day 1 (odds ratio 2.86; 95% confidence interval 1.18–6.93; p = 0.02). Pre-operative neutrophil–lymphocyte ratio was not significantly associated with time to inotrope free or vasoactive-inotrope score. Post-operative neutrophil–lymphocyte ratio was also not associated with outcomes. In children after congenital heart surgery, higher pre-operative neutrophil–lymphocyte ratio was associated with a higher chance of low cardiac output in the early post-operative period. Pre-operative neutrophil–lymphocyte ratio maybe a useful prognostic marker in children undergoing congenital heart surgery.
Non-tuberculous mycobacterium encephalitis is rare. Since 2013, a global outbreak of Mycobacterium chimaera infection has been attributed to point-source contamination of heater cooler units used in cardiac surgery. Disseminated M. chimaera infection has presented many unique challenges, including non-specific clinical presentations with delays in diagnosis, and a high mortality rate among predominantly immunocompetent adults. Here, we describe three patients with fatal disseminated Mycobacterium chimaera infection showing initially non-specific, progressively worsening neurocognitive decline, including confusion, delirium, depression and apathy. Autopsy revealed widespread granulomatous encephalitis of the cerebrum, brain stem and spinal cord, along with granulomatous chorioretinitis. Cerebral involvement and differentiation between mycobacterial granulomas and microangiopathic changes can be assessed best on MRI with contrast enhancement. The prognosis of M. chimaera encephalitis appears to be very poor, but might be improved by increased awareness of this new syndrome and timely antimicrobial treatment.
This presentation will enable the learner to:
1.Describe the clinical, radiological and neuropathological findings of Mycobacterium chimaera encephalitis
2.Be aware of this rare form of encephalitis, and explain its diagnosis, prognosis and management
The Developmental Origins of Disease hypothesis has spurred increased interest in how prenatal exposures affect lifelong health, while mechanisms such as epigenetics may explain the multigenerational influences on health. Such factors are not well captured within conventional epidemiologic study designs. We explored the feasibility of collecting information on the offspring and grand-offspring of participants in a long-running study.
The Bogalusa Heart Study is a study, begun in 1973, of life-course cardiovascular health in a semirural population (65% white and 35% black).
Female participants who had previously provided information on their pregnancies were contacted to obtain contact information for their daughters aged 12 and older. Daughters were then contacted to obtain reproductive histories, and invited for a clinic or lab visit to measure cardiovascular risk factors.
Two hundred seventy-four daughters of 208 mothers were recruited; 81% (223) had a full clinic visit and 19% (51) a phone interview only. Forty-five percent of the daughters were black, and 55% white. Mean and median age at interview was 27, with 15% under the age of 18. The strongest predictors of participation were black race, recent maternal participation in the parent study, and living in or near Bogalusa. Simple correlations for cardiovascular risk factors across generations were between r = 0.19 (systolic blood pressure) and r = 0.39 (BMI, LDL).
It is feasible to contact the children of study participants even when participants are adults, and initial information on the grandchildren can also be determined in this manner.
We assessed the impact of an embedded electronic medical record decision-support matrix (Cerner software system) for the reduction of hospital-onset Clostridioides difficile. A critical review of 3,124 patients highlighted excessive testing frequency in an academic medical center and demonstrated the impact of decision support following a testing fidelity algorithm.
Cardiac surgery-associated acute kidney injury is common. In order to improve our understanding of acute kidney injury, we formed the multi-centre Neonatal and Pediatric Heart and Renal Outcomes Network. Our main goals are to describe neonatal kidney injury epidemiology, evaluate variability in diagnosis and management, identify risk factors, investigate the impact of fluid overload, and explore associations with outcomes.
The Neonatal and Pediatric Heart and Renal Outcomes Network collaborative includes representatives from paediatric cardiac critical care, cardiology, nephrology, and cardiac surgery. The collaborative sites and infrastructure are part of the Pediatric Cardiac Critical Care Consortium. An acute kidney injury module was developed and merged into the existing infrastructure. A total of twenty-two participating centres provided data on 100–150 consecutive neonates who underwent cardiac surgery within the first 30 post-natal days. Additional acute kidney injury variables were abstracted by chart review and merged with the corresponding record in the quality improvement database. Exclusion criteria included >1 operation in the 7-day study period, pre-operative renal replacement therapy, pre-operative serum creatinine >1.5 mg/dl, and need for extracorporeal support in the operating room or within 24 hours after the index operation.
A total of 2240 neonatal patients were enrolled across 22 centres. The incidence of acute kidney injury was 54% (stage 1 = 31%, stage 2 = 13%, and stage 3 = 9%).
Neonatal and Pediatric Heart and Renal Outcomes Network represents the largest multi-centre study of neonatal kidney injury. This new network will enhance our understanding of kidney injury and its complications.
This foreign policy analysis textbook is written especially for students studying to become national security professionals. It translates academic knowledge about the complex influences on American foreign policymaking into an intuitive, cohesive, and practical set of analytic tools. The focus here is not theory for the sake of theory, but rather to translate theory into practice. Classic paradigms are adapted to fit the changing realities of the contemporary national security environment. For example, the growing centrality of the White House is seen in the 'palace politics' of the president's inner circle, and the growth of the national security apparatus introduces new dimensions to organizational processes and subordinate levels of bureaucratic politics. Real-world case studies are used throughout to allow students to apply theory. These comprise recent events that draw impartially across partisan lines and encompass a variety of diplomatic, military, and economic and trade issues.