Cognitive Changes and Quality of Life in Neurocysticercosis: A Longitudinal Study

Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system. Cognitive changes have been frequently reported with this disease but have not been well studied. Our study team recruited a group of new onset NCC cases and a matched set of healthy neighborhood controls and new onset epilepsy controls in Lima, Peru for this study. A neuropsychological battery was administered at baseline and at 6 months to all groups. Brain MRI studies were also obtained on NCC cases at baseline and at 6 months. Newly diagnosed patients with NCC had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment. This study is the first to assess cognitive status and quality of life longitudinally in patients with NCC and provides new data on an important clinical morbidity outcome

Sickness behaviour pushed too far – the basis of the syndrome seen in severe protozoal, bacterial and viral diseases and post-trauma

Certain distinctive components of the severe systemic inflammatory syndrome are now well-recognized to be common to malaria, sepsis, viral infections, and post-trauma illness. While their connection with cytokines has been appreciated for some time, the constellation of changes that comprise the syndrome has simply been accepted as an empirical observation, with no theory to explain why they should coexist. New data on the effects of the main pro-inflammatory cytokines on the genetic control of sickness behaviour can be extended to provide a rationale for why this syndrome contains many of its accustomed components, such as reversible encephalopathy, gene silencing, dyserythropoiesis, seizures, coagulopathy, hypoalbuminaemia and hypertriglyceridaemia. It is thus proposed that the pattern of pathology that comprises much of the systemic inflammatory syndrome occurs when one of the usually advantageous roles of pro-inflammatory cytokines – generating sickness behaviour by moderately repressing genes (Dbp, Tef, Hlf, Per1, Per2 and Per3, and the nuclear receptor Rev-erbα) that control circadian rhythm – becomes excessive. Although reversible encephalopathy and gene silencing are severe events with potentially fatal consequences, they can be viewed as having survival advantages through lowering energy demand. In contrast, dyserythropoiesis, seizures, coagulopathy, hypoalbuminaemia and hypertriglyceridaemia may best be viewed as unfortunate consequences of extreme repression of these same genetic controls when the pro-inflammatory cytokines that cause sickness behaviour are produced excessively. As well as casting a new light on the previously unrationalized coexistence of these aspects of systemic inflammatory diseases, this concept is consistent with the case for a primary role for inflammatory cytokines in their pathogenesis across this range of diseases

Ebola: translational science considerations

We are currently in the midst of the most aggressive and fulminating outbreak of Ebola-related disease, commonly referred to as “Ebola”, ever recorded. In less than a year, the Ebola virus (EBOV, Zaire ebolavirus species) has infected over 10,000 people, indiscriminately of gender or age, with a fatality rate of about 50%. Whereas at its onset this Ebola outbreak was limited to three countries in West Africa (Guinea, where it was first reported in late March 2014, Liberia, where it has been most rampant in its capital city, Monrovia and other metropolitan cities, and Sierra Leone), cases were later reported in Nigeria, Mali and Senegal, as well as in Western Europe (i.e., Madrid, Spain) and the US (i.e., Dallas, Texas; New York City) by late October 2014. World and US health agencies declared that the current Ebola virus disease (EVD) outbreak has a strong likelihood of growing exponentially across the world before an effective vaccine, treatment or cure can be developed, tested, validated and distributed widely. In the meantime, the spread of the disease may rapidly evolve from an epidemics to a full-blown pandemic. The scientific and healthcare communities actively research and define an emerging kaleidoscope of knowledge about critical translational research parameters, including the virology of EBOV, the molecular biomarkers of the pathological manifestations of EVD, putative central nervous system involvement in EVD, and the cellular immune surveillance to EBOV, patient-centered anthropological and societal parameters of EVD, as well as translational effectiveness about novel putative patient-targeted vaccine and pharmaceutical interventions, which hold strong promise, if not hope, to curb this and future Ebola outbreaks. This work reviews and discusses the principal known facts about EBOV and EVD, and certain among the most interesting ongoing or future avenues of research in the field, including vaccination programs for the wild animal vectors of the virus and the disease from global translational science perspective

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

A Data Science Platform to Enable Time-domain Astronomy

SkyPortal is an open-source software package designed to discover interesting transients efficiently, manage follow-up, perform characterization, and visualize the results. By enabling fast access to archival and catalog data, crossmatching heterogeneous data streams, and the triggering and monitoring of on-demand observations for further characterization, a SkyPortal-based platform has been operating at scale for >2 yr for the Zwicky Transient Facility Phase II community, with hundreds of users, containing tens of millions of time-domain sources, interacting with dozens of telescopes, and enabling community reporting. While SkyPortal emphasizes rich user experiences across common front-end workflows, recognizing that scientific inquiry is increasingly performed programmatically, SkyPortal also surfaces an extensive and well-documented application programming interface system. From back-end and front-end software to data science analysis tools and visualization frameworks, the SkyPortal design emphasizes the reuse and leveraging of best-in-class approaches, with a strong extensibility ethos. For instance, SkyPortal now leverages ChatGPT large language models to generate and surface source-level human-readable summaries automatically. With the imminent restart of the next generation of gravitational-wave detectors, SkyPortal now also includes dedicated multimessenger features addressing the requirements of rapid multimessenger follow-up: multitelescope management, team/group organizing interfaces, and crossmatching of multimessenger data streams with time-domain optical surveys, with interfaces sufficiently intuitive for newcomers to the field. This paper focuses on the detailed implementations, capabilities, and early science results that establish SkyPortal as a community software package ready to take on the data science challenges and opportunities presented by this next chapter in the multimessenger era

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

EXPERIMENTAL AND FINITE-ELEMENT STUDIES ON MODE-I AND MIXED-MODE (I AND II) STABLE CRACK-GROWTH .2. FINITE-ELEMENT ANALYSIS

Finite element studies are presented on both mode I and mixed mode stable crack growth under static loadings through an aluminium (D16AT) alloy. A COD based criterion has been used to predict the load-displacement diagram from initiation to instability. The theoretical predictions are compared with experimental results presented in Part I. Results on computed crack profiles, stress-strain distribution ahead of the crack tip, J integrals, J resistance curves, plastic zones, etc., are included. The study indicates that the load-displacement diagram associated with a mixed mode stable crack growth in a compact tension type of specimen geometry can be predicted reasonably accurately using the criterion of a fixed crack opening displacement at a finite distance behind the crack tip provided the crack is allowed to grow in the direction of initial growth in the finite element analysis. The crack assumes a more blunted profile in a mixed mode than in the mode I at all the stages of stable extension. The distributions of normal stress and strain in the direction perpendicular to the crack extension line, ahead of the current crack tip, have similarities between the mode I and mixed mode, irrespective of loading angle. Both the stress and strain levels increase as the crack extension proceeds. In a mixed mode, the J integral at the onset of crack extension is the lowest compared with the values at the later stages of the extension. Further, the tearing modulus associated with initial kinking is very small; it becomes close to the mode I values at the later stages. The tearing modulus remained approximately constant during the whole mode I stable growth and it had a similar trend subsequent to kinking in a mixed mode. The specific work of crack extension is zero as DELTA-a-->0 and it increases gradually with DELTA-a irrespective of the mode of loading; the actual variation depends on the loading angle. The plastic zone size grows as the stable extension progresses; the growth is approximately the maximum along the crack extension line

EXPERIMENTAL AND FINITE-ELEMENT STUDIES ON MODE-I AND MIXED-MODE (I AND II) STABLE CRACK-GROWTH .1. EXPERIMENTAL

Experimental results on mode I and mixed mode stable crack growth under static loadings through an aluminium alloy (D16AT) are presented. The compact tension type of geometry was employed for both the sets of tests. Data pertaining to load-deflection diagrams, crack opening displacements, crack front geometry, etc., are included. There is a greater spurt of crack growth at the initiation stage in a mixed mode than in mode I. The crack opening angle (COA) remained nearly constant during the whole stable growth. There is a substantial tunneling, the extent of which increases as the extension progresses in both mode I and mixed mode. The tunneling reduces as the ratio a(0)/W increases. Because of this tunneling, the COD at a point finite distance behind the crack tip and on the specimen surface is much more than expected. At the maximum load the tunneling is 2 to 3.5 mm in the case of mode I. The crack extends intially almost along a straight line at an angle with the initial crack in a mixed mode. The maximum to initiation load ratio varied in the range 1.50 to 1.75 for the whole range of tests