Ailing, Aging, Addicted: Studies of Compromised Leadership

What role did drug abuse play in John F. Kennedy\u27s White House, and how was it kept from the public? How did general anesthetics and aging affect the presidency of Ronald Reagan? Why did Winston Churchill become more egocentric, Woodrow Wilson more self- righteous, and Josef Stalin more paranoid as they aged—and how did those qualities alter the course of history? Was Napoleon poisoned with arsenic or did underlying disease account for his decline at the peak of his power? Does syphilis really explain Henry VIII\u27s midlife transformation? Was there more than messianism brewing in the brains of some zealots of the past, among them Adolf Hitler, Joan of Arc, and John Brown? Most important of all, when does one man\u27s illness cause millions to suffer, and when is it merely a footnote to history? To answer such questions requires the clinical intuition of a practicing physician and the scholarly perspective of a trained historian. Bert Park, who qualifies on both counts, offers here fascinating second opinions, basing his retrospective diagnoses on a wide range of sources from medicine and history. Few books so graphically portray the impact on history of physiologically compromised leadership, misdiagnosis, and inappropriate medical treatment. Park not only untangles medical mysteries from the past but also offers timely suggestions for dealing with such problems in the future. As a welcome sequel to his first work, The Impact of Illness on World Leaders, this book offers scholars, physicians, and general readers an entertaining, albeit sobering, analysis. Bert E. Park, M.D., is a practicing neurological surgeon, an adjunct professor of history, and a member of the Editorial Advisory Committee of the Papers of Woodrow Wilson. Historians will be grateful for Park\u27s meticulous and wide-ranging citations and well-crafted index. This book will entertain, provoke, and stimulate historians, physicians, and general readers alike, and should stimulate further scholarship concerning the pathography of world leaders. —Bulletin of the History of Medicinehttps://uknowledge.uky.edu/upk_history_in_general/1003/thumbnail.jp

When to hold that thought: an experimental study showing reduced inhibition of pre-trained associations in schizophrenia.

Schizophrenia encompasses a wide variety of cognitive dysfunctions, a number of which can be understood as deficits of inhibition. To date, no research has examined ‘conditioned inhibition’ in schizophrenia - the ability of a stimulus that signals the absence of an expected outcome to counteract the conditioned response produced by a signal for that outcome (a conditioned excitor). A computer-based task was used to measure conditioned excitation and inhibition in the same discrimination procedure, in 25 patients with a confirmed diagnosis of schizophrenia and a community-based comparison sample. Conditioned inhibition was measured by a ratio score, which compared the degree to which the inhibitory stimulus and a neutral control stimulus reduced conditioned responding to the excitatory cue: the lower the ratio, the greater the inhibitory learning. At test the ratios were 0.45 and 0.39 for patient and control groups respectively, and the relevant interaction term of the ANOVA confirmed that the degree of inhibition was reduced in the patient group, with an effect size of r = 0.28. These results demonstrate for the first time that inhibitory learning is impaired in schizophrenia. Such an impairment provides an attractive framework for the interpretation of the positive symptoms of schizophrenia. However, we were unable to demonstrate any relationship between the level of conditioned inhibition and medication. Similarly, in the present study it must be emphasised that the available data did not demonstrate any relationship between individual variation in inhibitory learning and the level of positive symptoms as measured by the PANSS. In fact inhibitory learning impairment was relatively greater in participants with a predominantly negative symptom profile and their excitatory learning was also reduced. Accordingly the next step will be to investigate such relationships in a larger sample with a priori defined sub-groups displaying predominantly positive versus predominantly negative symptoms

Abnormalities in structural covariance of cortical gyrification in schizophrenia

The highly convoluted shape of the adult human brain results from several well-coordinated maturational events that start from embryonic development and extend through the adult life span. Disturbances in these maturational events can result in various neurological and psychiatric disorders, resulting in abnormal patterns of morphological relationship among cortical structures (structural covariance). Structural covariance can be studied using graph theory-based approaches that evaluate topological properties of brain networks. Covariance-based graph metrics allow cross-sectional study of coordinated maturational relationship among brain regions. Disrupted gyrification of focal brain regions is a consistent feature of schizophrenia. However, it is unclear if these localized disturbances result from a failure of coordinated development of brain regions in schizophrenia. We studied the structural covariance of gyrification in a sample of 41 patients with schizophrenia and 40 healthy controls by constructing gyrification-based networks using a 3-dimensional index. We found that several key regions including anterior insula and dorsolateral prefrontal cortex show increased segregation in schizophrenia, alongside reduced segregation in somato-sensory and occipital regions. Patients also showed a lack of prominence of the distributed covariance (hubness) of cingulate cortex. The abnormal segregated folding pattern in the right peri-sylvian regions (insula and fronto-temporal cortex) was associated with greater severity of illness. The study of structural covariance in cortical folding supports the presence of subtle deviation in the coordinated development of cortical convolutions in schizophrenia. The heterogeneity in the severity of schizophrenia could be explained in part by aberrant trajectories of neurodevelopment

Instanton Induced Neutrino Majorana Masses in CFT Orientifolds with MSSM-like spectra

Recently it has been shown that string instanton effects may give rise to neutrino Majorana masses in certain classes of semi-realistic string compactifications. In this paper we make a systematic search for supersymmetric MSSM-like Type II Gepner orientifold constructions admitting boundary states associated with instantons giving rise to neutrino Majorana masses and other L- and/or B-violating operators. We analyze the zero mode structure of D-brane instantons on general type II orientifold compactifications, and show that only instantons with O(1) symmetry can have just the two zero modes required to contribute to the 4d superpotential. We however discuss how the addition of fluxes and/or possible non-perturbative extensions of the orientifold compactifications would allow also instantons with $Sp(2)$ and U(1) symmetries to generate such superpotentials. In the context of Gepner orientifolds with MSSM-like spectra, we find no models with O(1) instantons with just the required zero modes to generate a neutrino mass superpotential. On the other hand we find a number of models in one particular orientifold of the Gepner model $(2,4,22,22)$ with $Sp(2)$ instantons with a few extra uncharged non-chiral zero modes which could be easily lifted by the mentioned effects. A few more orientifold examples are also found under less stringent constraints on the zero modes. This class of $Sp(2)$ instantons have the interesting property that R-parity conservation is automatic and the flavour structure of the neutrino Majorana mass matrices has a simple factorized form.Comment: 68 pages, 2 figures; v2. typos corrected, refs adde

A Case of Bacteremia by Neisseria gonorrhoeae Coincident with Massive Hemorrhage of Esophageal Varices

A 42-yr-old man with hepatitis B virus associated liver cirrhosis was admitted to the emergency room because of multiple seizures, a history of chills and myalgia over the previous 2 weeks, and 3 days of melena. He was febrile with a temperature of 38.0℃. There were no symptoms and signs related to the genitourinary system, skin, or joints. Three sets of blood cultures were obtained and oxidase-positive, gram-negative diplococci were detected after 25.9-26.9 hr of incubation in all aerobic vials. The organism was positive for catalase and oxidase, and was identified as Neisseria gonorrhoeae, using a Vitek Neisseria-Haemophilus Identification card (bioMérieux Vitek, Inc., USA). Further, 16S rRNA sequencing of this isolate revealed a 99.9% homology with the published sequence of N. gonorrhoeae strain NCTC 83785 (GenBank Accession No. NR_026079.1). Acute bleeding by variceal rupture seems to be a likely route of introduction of N. gonorrhoeae from the mucosa into the blood. To the best of our knowledge, this is the first case of gonococcal bacteremia in Korea

Prognostic Significance of Infection Acquisition Sites in Spontaneous Bacterial Peritonitis: Nosocomial versus Community Acquired

Spontaneous bacterial peritonitis (SBP) is an ascitic fluid infection as a complication of end stage liver disease. The outcome is related to the severity of hepatorenal function, gastrointestinal bleeding, and many others; however it is not well known whether the infection acquisition sites have an effect on the prognosis of SBP. In order to identify the prognostic significance of the acquisition sites, we studied 106 patients who were diagnosed as culture positive SBP between October 1998 and August 2003. Thirty-two episodes were nosocomial and 74 were community acquired. Gram-negative bacilli such as Escherichia coli were dominant in both of the nosocomial and community-acquired SBPs. Despite significantly higher resistance to cefotaxime in nosocomial isolates compared to community-acquired isolates (77.8% vs. 13.6%, p=0.001), no difference was found regarding short or long term prognosis. Infection acquisition sites were not related to short or long term prognosis either. Shock, gastrointestinal bleeding and renal dysfunction were related to short term prognosis. Only Child-Pugh class C was identified as an independent prognostic factor of long-term survival