Selective cerebral hypothermia for post-hypoxic neuroprotection in neonates using a solid ice cap

No Abstract. South African Medical Journal Vol. 96(9) (Part 2) 2006: 976-98

Why do we talk to ourselves?

Human beings talk to themselves; sometimes out-loud, other times in inner speech. In this paper, I present a resolution to the following dilemma that arises from self-talk. If self-talk exists then either, (i) we know what we are going to say and self-talk serves no communicative purpose, and must serve some other purpose, or (ii) we don’t know what we are going to say, and self-talk does serve a communicative purpose, namely, it is an instance of us communicating with ourselves. Adopting (i) was the strategy taken by Bart Geurts, who claims that the primary purpose of self-talk is to entrain commitments, and is not (primarily) communicative. While accepting that self-talk can usefully play this role, I criticise the view that entraining commitments is self-talk’s fundamental role. I argue that adopting the view that we are self-blind, at least to a significant degree, means that we can accept that self-talk does play a communicative role

Phototherapy and exchange transfusion for neonatal hyperbilirubinaemia

The purpose of this document is to address the current lack of consensus  regarding the management of hyperbilirubinaemia in neonates in South Africa. If left untreated, severe neonatal hyperbilirubinaemia may cause kernicterus and ultimately death and the severity of neonatal jaundice is often underestimated clinically. However, if phototherapy is instituted  timeously and at the correct intensity an exchange transfusion can usually be avoided. The literature describing intervention thresholds for  phototherapy and exchange transfusion in both term and preterm infants is therefore reviewed and specific intervention thresholds that can be used throughout South Africa are proposed and presented graphically. A simplified version for use in a primary care setting is also presented. All academic heads of neonatology departments throughout South Africa were consulted in the process of drawing up this document and consensus was achieved

Positive definite metric spaces

Magnitude is a numerical invariant of finite metric spaces, recently introduced by T. Leinster, which is analogous in precise senses to the cardinality of finite sets or the Euler characteristic of topological spaces. It has been extended to infinite metric spaces in several a priori distinct ways. This paper develops the theory of a class of metric spaces, positive definite metric spaces, for which magnitude is more tractable than in general. Positive definiteness is a generalization of the classical property of negative type for a metric space, which is known to hold for many interesting classes of spaces. It is proved that all the proposed definitions of magnitude coincide for compact positive definite metric spaces and further results are proved about the behavior of magnitude as a function of such spaces. Finally, some facts about the magnitude of compact subsets of l_p^n for p \le 2 are proved, generalizing results of Leinster for p=1,2, using properties of these spaces which are somewhat stronger than positive definiteness.Comment: v5: Corrected some misstatements in the last few paragraphs. Updated reference

Methodological quality of systematic reviews of animal studies: a survey of reviews of basic research

BACKGROUND: Systematic reviews can serve as a tool in translation of basic life sciences research from laboratory to human research and healthcare. The extent to which reviews of animal research are systematic and unbiased is not known. METHODS: We searched, without language restrictions, Medline, Embase, bibliographies of known reviews (1996–2004) and contacted experts to identify citations of reviews of basic science literature which, as a minimum, performed search of a publicly available resource. From these we identified reviews of animal studies where laboratory variables were measured or where treatments were administered to live animals to examine their effects, and compared them with reviews of bench studies in which human or animal tissues, cell systems or organ preparations were examined in laboratories to better understand mechanisms of diseases. RESULTS: Systematic reviews of animal studies often lacked methodological features such as specification of a testable hypothesis (9/30, 30%); literature search without language restriction (8/30, 26.6%); assessment of publication bias (5/30, 16.6%), study validity (15/30, 50%) and heterogeneity (10/30, 33.3%); and meta-analysis for quantitative synthesis (12/30, 40%). Compared to reviews of bench studies, they were less prone to bias as they specified the question (96.6% vs. 80%, p = 0.04), searched multiple databases (60% vs. 26.6%, p = 0.01), assessed study quality (50% vs. 20%, p = 0.01), and explored heterogeneity (33.3% vs. 2.2%, p = 0.001) more often. CONCLUSION: There seems to be a gradient of frequency of methodological weaknesses among reviews: Attempted systematic reviews of whole animal research tend to be better than those of bench studies, though compared to systematic reviews of human clinical trials they are apparently poorer. There is a need for rigour when reviewing animal research

Would the field of cognitive neuroscience be advanced by sharing functional MRI data?

During the past two decades, the advent of functional magnetic resonance imaging (fMRI) has fundamentally changed our understanding of brain-behavior relationships. However, the data from any one study add only incrementally to the big picture. This fact raises important questions about the dominant practice of performing studies in isolation. To what extent are the findings from any single study reproducible? Are researchers who lack the resources to conduct a fMRI study being needlessly excluded? Is pre-existing fMRI data being used effectively to train new students in the field? Here, we will argue that greater sharing and synthesis of raw fMRI data among researchers would make the answers to all of these questions more favorable to scientific discovery than they are today and that such sharing is an important next step for advancing the field of cognitive neuroscience

California Men's Health Study (CMHS): a multiethnic cohort in a managed care setting

BACKGROUND: We established a male, multiethnic cohort primarily to study prostate cancer etiology and secondarily to study the etiologies of other cancer and non-cancer conditions. METHODS/DESIGN: Eligible participants were 45-to-69 year old males who were members of a large, prepaid health plan in California. Participants completed two surveys on-line or on paper in 2002 – 2003. Survey content included demographics; family, medical, and cancer screening history; sexuality and sexual development; lifestyle (diet, physical activity, and smoking); prescription and non-prescription drugs; and herbal supplements. We linked study data with clinical data, including laboratory, hospitalization, and cancer data, from electronic health plan files. We recruited 84,170 participants, approximately 40% from minority populations and over 5,000 who identified themselves as other than heterosexual. We observed a wide range of education (53% completed less than college) and income. PSA testing rates (75% overall) were highest among black participants. Body mass index (BMI) (median 27.2) was highest for blacks and Latinos and lowest for Asians, and showed 80.6% agreement with BMI from clinical data sources. The sensitivity and specificity can be assessed by comparing self-reported data, such as PSA testing, diabetes, and history of cancer, to health plan data. We anticipate that nearly 1,500 prostate cancer diagnoses will occur within five years of cohort inception. DISCUSSION: A wide variety of epidemiologic, health services, and outcomes research utilizing a rich array of electronic, biological, and clinical resources is possible within this multiethnic cohort. The California Men's Health Study and other cohorts nested within comprehensive health delivery systems can make important contributions in the area of men's health

High-dose chemotherapy and autologous stem cell rescue for atypical teratoid/rhabdoid tumor of the central nervous system

Atypical Teratoid/Rhabdoid tumors (AT/RT) of the central nervous system are rare but aggressive tumors of childhood. Median survival with surgery and standard chemotherapy is less than 12 months. In an attempt to improve outcome, patients were treated with aggressive surgical resection and multi-agent chemotherapy, followed by high dose chemotherapy with autologous stem cell rescue. Nine consecutive children (median age 21 months) were diagnosed with AT/RT at the University of California San Francisco Childrens Hospital from 1997 to 2007 and treated with this aggressive approach. Diagnosis was confirmed using molecular markers. There are two long-term survivors (78 and 98 months from diagnosis). One additional patient is alive with disease. Three patients died of disease during therapy. Three patients died of disease after therapy was complete. There were no toxic deaths. Two of nine patients treated for AT/RT at our institution with high dose chemotherapy and autologous bone marrow transplant are long-term survivors, suggesting that a subset of patients can be cured with this approach

Nature of protein family signatures: Insights from singular value analysis of position-specific scoring matrices

Position-specific scoring matrices (PSSMs) are useful for detecting weak homology in protein sequence analysis, and they are thought to contain some essential signatures of the protein families. In order to elucidate what kind of ingredients constitute such family-specific signatures, we apply singular value decomposition to a set of PSSMs and examine the properties of dominant right and left singular vectors. The first right singular vectors were correlated with various amino acid indices including relative mutability, amino acid composition in protein interior, hydropathy, or turn propensity, depending on proteins. A significant correlation between the first left singular vector and a measure of site conservation was observed. It is shown that the contribution of the first singular component to the PSSMs act to disfavor potentially but falsely functionally important residues at conserved sites. The second right singular vectors were highly correlated with hydrophobicity scales, and the corresponding left singular vectors with contact numbers of protein structures. It is suggested that sequence alignment with a PSSM is essentially equivalent to threading supplemented with functional information. The presented method may be used to separate functionally important sites from structurally important ones, and thus it may be a useful tool for predicting protein functions.Comment: 22 pages, 7 figures, 4 table

Contrasting prefrontal cortex contributions to episodic memory dysfunction in behavioural variant frontotemporal dementia and alzheimer's disease

Recent evidence has questioned the integrity of episodic memory in behavioural variant frontotemporal dementia (bvFTD), where recall performance is impaired to the same extent as in Alzheimer's disease (AD). While these deficits appear to be mediated by divergent patterns of brain atrophy, there is evidence to suggest that certain prefrontal regions are implicated across both patient groups. In this study we sought to further elucidate the dorsolateral (DLPFC) and ventromedial (VMPFC) prefrontal contributions to episodic memory impairment in bvFTD and AD. Performance on episodic memory tasks and neuropsychological measures typically tapping into either DLPFC or VMPFC functions was assessed in 22 bvFTD, 32 AD patients and 35 age- and education-matched controls. Behaviourally, patient groups did not differ on measures of episodic memory recall or DLPFC-mediated executive functions. BvFTD patients were significantly more impaired on measures of VMPFC-mediated executive functions. Composite measures of the recall, DLPFC and VMPFC task scores were covaried against the T1 MRI scans of all participants to identify regions of atrophy correlating with performance on these tasks. Imaging analysis showed that impaired recall performance is associated with divergent patterns of PFC atrophy in bvFTD and AD. Whereas in bvFTD, PFC atrophy covariates for recall encompassed both DLPFC and VMPFC regions, only the DLPFC was implicated in AD. Our results suggest that episodic memory deficits in bvFTD and AD are underpinned by divergent prefrontal mechanisms. Moreover, we argue that these differences are not adequately captured by existing neuropsychological measures