Lymphatic network drainage resolves cerebral edema and facilitates recovery from experimental cerebral malaria.

While brain swelling, associated with fluid accumulation, is a known feature of pediatric cerebral malaria (CM), how fluid and macromolecules are drained from the brain during recovery from CM is unknown. Using the experimental CM (ECM) model, we show that fluid accumulation in the brain during CM is driven by vasogenic edema and not by perivascular cerebrospinal fluid (CSF) influx. We identify that fluid and molecules are removed from the brain extremely quickly in mice with ECM to the deep cervical lymph nodes (dcLNs), predominantly through basal routes and across the cribriform plate and the nasal lymphatics. In agreement, we demonstrate that ligation of the afferent lymphatic vessels draining to the dcLNs significantly impairs fluid drainage from the brain and lowers anti-malarial drug recovery from the ECM syndrome. Collectively, our results provide insight into the pathways that coordinate recovery from CM

EMPIRIC ANALYSIS OF EXTERNAL DEBT IN CROATIA: VAR MODEL APPROACH

Djelovanje različitih endogenih i egzogenih faktora zaduženosti dovelo je u posljednjem desetljeću do naglog porasta inozemne zaduženosti u Hrvatskoj. Udio bruto inozemnog duga u bruto domaćem proizvodu je premašio razinu od 100 posto uz pogoršanje pokazatelja inozemne zaduženosti, a problem inozemne zaduženosti se nadvio kao Damoklov mač nad hrvatskim gospodarstvom. Cilj rada je istražiti međuovisnost čimbenika koji su doveli do naglog rasta inozemne zaduženosti u Hrvatskoj i dati prijedlog mjera za rješenje problema inozemne zaduženosti zemlje. Determinante inozemne zaduženosti koje se koriste u ekonometrijskoj analizi su deficit trgovinske (robne) razmjene, realni efektivni tečaj kune, kamatni diferencijal i deficit državnog proračuna. Da bi se istražila dinamička međuovisnost varijabli formiran je VAR model koji pretpostavlja da su sve varijable u modelu potencijalno endogene. Koristi se Grangerov test uzročnosti radi određivanja ispravnog poretka varijabli u faktorizaciji, a testom impulsnog odziva prikazuju se reakcije bruto inozemnog duga na promjene ključnih varijabli za dvije standardne devijacije u kratkom i dugom roku. Rezultati Grangerovog testa uzročnosti su pokazali da postoji uzročna veza u smjeru od deficita državnog proračuna i robne razmjene prema bruto inozemnom dugu. S druge strane, postoji uzročna veza u smjeru od bruto inozemnog duga prema kamatnom diferencijalu. Dekompozicija varijanci prognostičkih pogrešaka je pokazala da najveći značaj u objašnjenju varijabiliteta bruto inozemnog duga imaju varijable deficit državnog proračuna i deficit tekućeg računa bilance plaćanja.The sharp rise of external debt in Croatia in the last decade was the result of different endogenous and exogenous factors of external indebtedness. The share of gross external debt to gross domestic product has exceeded the ratio of 100 percent while worsening other indicators of external debt. Symbolically speaking the problem of external debt hangs like a Damocles sword over the Croatian economy. The aim of this paper is to explore the interdependence between the factors which led to a sharp increase of foreign debt in Croatia and to suggest the measures to overcome the problem of indebtedness. Determinants of external debt used in the econometric analysis are merchandise trade deficit, real effective exchange rate, interest rate differential and the budget deficit. In order to investigate the dynamic interdependence between the variables econometric VAR model was built. It assumes that all variables in the model are potentially endogenous. Granger causality test was used to determine the correct order of variables in factorization while the test of impulse responses explains the reaction of the gross external debt to two standard deviation changes in key variables in the short and the long run. The results of Granger causality tests have shown that there is a causal relationship in the direction from budget and merchandise trade deficit to gross external debt. On the other hand, there is a causal relationship in the direction from the gross external debt to interest rate differential. Forecast error variance decomposition has shown that the greatest importance in explaining the variability of the gross external debt has budget deficit and current account deficit

Health, education, and social care provision after diagnosis of childhood visual disability

Aim: To investigate the health, education, and social care provision for children newly diagnosed with visual disability.Method: This was a national prospective study, the British Childhood Visual Impairment and Blindness Study 2 (BCVIS2), ascertaining new diagnoses of visual impairment or severe visual impairment and blindness (SVIBL), or equivalent vi-sion. Data collection was performed by managing clinicians up to 1-year follow-up, and included health and developmental needs, and health, education, and social care provision.Results: BCVIS2 identified 784 children newly diagnosed with visual impairment/SVIBL (313 with visual impairment, 471 with SVIBL). Most children had associated systemic disorders (559 [71%], 167 [54%] with visual impairment, and 392 [84%] with SVIBL). Care from multidisciplinary teams was provided for 549 children (70%). Two-thirds (515) had not received an Education, Health, and Care Plan (EHCP). Fewer children with visual impairment had seen a specialist teacher (SVIBL 35%, visual impairment 28%, χ2p < 0.001), or had an EHCP (11% vs 7%, χ2p < 0 . 01).Interpretation: Families need additional support from managing clinicians to access recommended complex interventions such as the use of multidisciplinary teams and educational support. This need is pressing, as the population of children with visual impairment/SVIBL is expected to grow in size and complexity.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

T cell autoreactivity directed toward CD1c itself rather than toward carried self lipids

The hallmark function of αβ T cell antigen receptors (TCRs) involves the highly specific co-recognition of a major histocompatibility complex molecule and its carried peptide. However, the molecular basis of the interactions of TCRs with the lipid antigen–presenting molecule CD1c is unknown. We identified frequent staining of human T cells with CD1c tetramers across numerous subjects. Whereas TCRs typically show high specificity for antigen, both tetramer binding and autoreactivity occurred with CD1c in complex with numerous, chemically diverse self lipids. Such extreme polyspecificity was attributable to binding of the TCR over the closed surface of CD1c, with the TCR covering the portal where lipids normally protrude. The TCR essentially failed to contact lipids because they were fully seated within CD1c. These data demonstrate the sequestration of lipids within CD1c as a mechanism of autoreactivity and point to small lipid size as a determinant of autoreactive T cell responses

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

Background: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. Methods: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. Findings: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96–1·28). Interpretation: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. Funding: National Institute for Health Research Health Services and Delivery Research Programme

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

BACKGROUND: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. METHODS: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. FINDINGS: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96-1·28). INTERPRETATION: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. FUNDING: National Institute for Health Research Health Services and Delivery Research Programme

Ontogenic time and worker longevity in the Australian stingless bee, Austroplebeia australis

Little is known about the biology and life cycle of the Australian stingless bee, Austroplebeia australis (Friese). The ontogenic times for developing offspring, as well as the longevity of adults, drive the overall life cycle of a social colony. The developmental times for brood within stingless bee species which build cluster-type nests, such as A. australis, are as yet unreported. A technique was developed whereby ‘donor’ brood cells were separated from the main brood cluster and ‘grafted’ into hive annexes, allowing workers from within the colony to access the brood ‘grafts’ for hygiene and maintenance activities, whilst enabling observation of developing brood. The mean ontogenic time for A. australis workers, maintained at ~27 °C, was 55 days, which is similar to that reported for other stingless bees. The maximum longevity of A. australis was determined by marking cohorts of worker bees within five colonies. Workers within all colonies demonstrated extended longevity, with an overall maximum longevity of 161 days, with the oldest bee living for 240 days. Extended longevity may result from evolutionary adaptations to the floral resource scarcity, which is regularly experienced in semi-arid, inland Australia, the natural habitat of A. australis

The thermal environment of nests of the Australian stingless bee, Austroplebeia australis

The greatest diversity of stingless bee species is found in warm tropical regions, where brood thermoregulation is unnecessary for survival. Although Austroplebeia australis (Friese) naturally occurs in northern regions of Australia, some populations experience extreme temperature ranges, including sub-zero temperatures. In this study, the temperature was monitored in A. australis colonies' brood chamber (n = 6) and the hive cavity (n = 3), over a 12-month period. The A. australis colonies demonstrated some degree of thermoconformity, i.e. brood temperature although higher correlated with cavity temperature, and were able to warm the brood chamber throughout the year. Brood production continued throughout the cold season and developing offspring survived and emerged, even after exposure to very low (-0.4 °C) and high (37.6 °C) temperatures. Austroplebeia australis, thus, demonstrated a remarkable ability to survive temperature extremes, which has not been seen in other stingless bee species

The Australian stingless bee industry : a follow-up survey, one decade on

In 2010, an online survey was conducted to assess the current status of the Australian stingless bee industry and its recent development. This was a follow-up survey conducted approximately one decade after the first study, by Heard and Dollin in 1998/99. It showed that the Australian industry had grown over the past ten or so years but is still underdeveloped. There was a 2.5-fold increase in the number of bee keepers and a 3.5 fold increase in the number of domesticated colonies. Seventy-eight percent of bee keepers were hobbyists, 54% of whom owned only one colony. Most colonies were kept in suburban areas. Two species, Tetragonula carbonaria and Austroplebeia australis, dominated the relatively short list of species kept. There was a high demand for Australian stingless bee colonies and their honey, but with less than 250 bee keepers currently propagating colonies, and many of them on a small scale, it is difficult to meet this demand. Pollination services were provided by less than 4% of the major stakeholders within the industry. Further research and development in the area of colony propagation may see this industry grow more quickly

Lymphatic network drainage resolves cerebral oedema and facilitates recovery from experimental cerebral malaria

SummaryWhilst brain swelling, associated with fluid accumulation, is a known feature ofpaediatric cerebral malaria (CM), how fluid and macromolecules are drained from the brain during recovery from CM is unknown. Using the experimental cerebral malaria model (ECM), we show that fluid accumulation in the brain during CM is driven by vasogenic oedema, and not by perivascular cerebrospinal fluid (CSF) influx. Fluid and molecules were removed from the brain extremely quickly in mice with ECM to the deep cervical lymph nodes (dcLNs), predominantly through basal routes and across the cribriform plate and the nasal lymphatics. In agreement, ligation of the afferent lymphatic vessels draining to the dcLNs significantly impaired fluid drainage from the brain, sustained brain swelling, and lowered anti-malarial drug recovery from the ECM syndrome. Collectively, our results show that CM is not due to damaged CNS fluid drainage pathways and provide new insight into the pathways that coordinate recovery from CM.<br/