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Elucidation of the structural basis of endothelial barrier function and the study of transcapillary fluid exchange dynamics are areas of active research. There has been significant enhancement in our understanding of the ultrastructural basis of endothelial barrier function. The role of glycocalyx has received special attention. Experimental evidence has called for a revision in the classic Starling principle of transcapillary exchange. The glycocalyx model provides a potential structural mechanism for the revised Starling principle. This knowledge can provide the framework for understanding the volume expansion effect of fluid therapy and the physiological basis of fluid therapy.

The rate of police-recorded assault more than doubled in NSW between 1990 and 2007. This bulletin investigates whether the increase was due to a genuine increase in violence or an increase in the amount and/or type of violent behaviour coming to police attention. Trends and patterns in police-recorded assault from 1995 to 2007 are supplemented with crime victim survey data, hospitalisations data and a selection of narratives for assault incidents. Over the period, rates of assault increased for both males and females and for all age groups. Increases occurred in both aggravated and common assault, assault with a weapon and without, in all statistical divisions and premise types. These trends in police-recorded assault, supported by increases in hospitalisation and victim survey data, suggest a real increase in violence. However, less serious police-recorded assaults (e.g. common assault and assault without a weapon) have increased at a greater rate than more serious assaults, and more recent assault narratives included a greater proportion of assaults with less serious actions. In addition, the increase in hospitalisations for assault was small in comparison to increases in police-recorded assault and crime survey victimisation rates. Thus, it is likely that the increase in assault was due not only to an increase in violence, but also to an increase in public awareness of assault and the increased willingness of victims and third parties to report, and/or police willingness to record, incidents as assault. [ABSTRACT FROM AUTHOR]

ABSTRACTThe ability to accurately diagnose malaria infections, particularly in settings where laboratory facilities are not well developed, is of key importance in the control of this disease. Rapid diagnostic tests (RDTs) offer great potential to address this need. Reports of significant variation in the field performance of RDTs based on the detection of Plasmodium falciparumhistidine-rich protein 2 (HRP2) (PfHRP2) and of significant sequence polymorphism in PfHRP2 led us to evaluate the binding of four HRP2-specific monoclonal antibodies (MABs) to parasite proteins from geographically distinct P. falciparumisolates, define the epitopes recognized by these MABs, and relate the copy number of the epitopes to MAB reactivity. We observed a significant difference in the reactivity of the same MAB to different isolates and between different MABs tested with single isolates. When the target epitopes of three of the MABs were determined and mapped onto the peptide sequences of the field isolates, significant variability in the frequency of these epitopes was observed. These findings support the role of sequence variation as an explanation for variations in the performance of HRP2-based RDTs and point toward possible approaches to improve their diagnostic sensitivities.

The article discusses the results on a study on the proportion of persons born in 1984 who have appeared in a criminal court before the age of 21 in New South Wales. About 9.9 percent of the cohort had at least one court appearance. Most of those persons who have appeared in court before the age of 21 appeared after the age of 18. About a third of those who have come out in the court for the first time are for driving-related offences.

ABSTRACTIndividuals in areas of intense malaria transmission exhibit resistance (or tolerance) to levels of parasitemia in their blood that would normally be associated with febrile illness in malaria-naïve subjects. The resulting level of parasitemia associated with illness (the pyrogenic threshold) is highest in childhood and lowest in adulthood. Clinical parallels between malarial and bacterial endotoxin tolerance have led to the supposition that both share common physiological processes, with nitric oxide (NO) proposed as a candidate mediator. The hypotheses that NO mediates tolerance and blood stage parasite killing in vivo were tested by determining its relationship to age and parasitemia cross-sectionally and longitudinally in a population of 195 children and adults from Papua New Guinea encountering intense malaria exposure. Despite pharmacological clearance of asymptomatic parasitemia, NO production and mononuclear cell NO synthase (NOS) activity were remarkably stable within individuals over time, were not influenced by parasitemia, and varied little with age. These results contrast with previous smaller cross-sectional studies. Baseline NO production and NOS activity did not protect against recurrent parasitemia, consistent with previous data suggesting that NO does not have antiparasitic effects against blood stage infection in vivo. The NO indices studied were markedly higher in specimens from study subjects than in samples from Australian controls, and NOS activity was significantly associated with plasma immunoglobulin E levels, consistent with induction of NO by chronic exposure to other infections and/or host genetic factors. These results suggest that NO is unlikely to mediate killing of blood stage parasites in this setting and is unlikely to be the primary mediator in the acquisition or maintenance of malarial tolerance.

ABSTRACTSulfadoxine is predominantly used in combination with pyrimethamine, commonly known as Fansidar, for the treatment of Plasmodium falciparum. This combination is usually less effective against Plasmodium vivax, probably due to the innate refractoriness of parasites to the sulfadoxine component. To investigate this mechanism of resistance by P. vivaxto sulfadoxine, we cloned and sequenced the P. vivax dhps(pvdhps) gene. The protein sequence was determined, and three-dimensional homology models of dihydropteroate synthase (DHPS) from P. vivaxas well as P. falciparumwere created. The docking of sulfadoxine to the two DHPS models allowed us to compare contact residues in the putative sulfadoxine-binding site in both species. The predicted sulfadoxine-binding sites between the species differ by one residue, V585 in P. vivax, equivalent to A613 in P. falciparum. V585 in P. vivaxis predicted by energy minimization to cause a reduction in binding of sulfadoxine to DHPS in P. vivaxcompared to P. falciparum. Sequencing dhpsgenes from a limited set of geographically different P. vivaxisolates revealed that V585 was present in all of the samples, suggesting that V585 may be responsible for innate resistance of P. vivaxto sulfadoxine. Additionally, amino acid mutations were observed in some P. vivaxisolates in positions known to cause resistance in P. falciparum, suggesting that, as in P. falciparum, these mutations are responsible for acquired increases in resistance of P. vivaxto sulfadoxine.

Mutations in the pfcrt and pfmdr1 genes have been associated with chloroquine resistance in Plasmodium falciparum. Ten and five mutations, respectively, have been identified in these genes from chloroquine-resistant parasites worldwide. Mutation patterns in pfcrt revealed that chloroquine resistance evolved independently in southeast Asia, South America, and Papua New Guinea. However, the evolution of chloroquine resistance in the rest of the Pacific region is unclear. In this study, we examined sequence polymorphisms in these genes in isolates from Morong, Philippines, and compared them to known chloroquine resistance sequences. Two novel mutations, A144T and L160Y, were identified outside of the 10 known mutations in pfcrt in Morong isolates. These novel mutations were identified only in parasites with K76T and N326D but without the common A220S mutation found in most chloroquine-resistant isolates. This represents a unique chloroquine resistance allelic type (K76T/A144T/L160Y/N326D) not previously found elsewhere in the world. One Morong isolate also had an additional C72S mutation, whereas only one isolate possessed an allelic type typical of chloroquine resistance in Asia. Parasites with the novel pfcrt allelic types were resistant to chloroquine in vitro and were unresponsive to verapamil (0.9 microM) chemosensitization, similar to chloroquine-resistant parasites from South America and Papua New Guinea. These results suggest that chloroquine resistance evolved independently in the Philippines and represents a second chloroquine resistance founder event in the South Pacific.

ABSTRACTMutations in the pfcrtand pfmdr1genes have been associated with chloroquine resistance in Plasmodium falciparum. Ten and five mutations, respectively, have been identified in these genes from chloroquine-resistant parasites worldwide. Mutation patterns in pfcrtrevealed that chloroquine resistance evolved independently in southeast Asia, South America, and Papua New Guinea. However, the evolution of chloroquine resistance in the rest of the Pacific region is unclear. In this study, we examined sequence polymorphisms in these genes in isolates from Morong, Philippines, and compared them to known chloroquine resistance sequences. Two novel mutations, A144T and L160Y, were identified outside of the 10 known mutations in pfcrtin Morong isolates. These novel mutations were identified only in parasites with K76T and N326D but without the common A220S mutation found in most chloroquine-resistant isolates. This represents a unique chloroquine resistance allelic type (K76T/A144T/L160Y/N326D) not previously found elsewhere in the world. One Morong isolate also had an additional C72S mutation, whereas only one isolate possessed an allelic type typical of chloroquine resistance in Asia. Parasites with the novel pfcrtallelic types were resistant to chloroquine in vitro and were unresponsive to verapamil (0.9 μM) chemosensitization, similar to chloroquine-resistant parasites from South America and Papua New Guinea. These results suggest that chloroquine resistance evolved independently in the Philippines and represents a second chloroquine resistance founder event in the South Pacific.

Provides guidelines to protect the body from toxic environment. Health consequences from polluted environment; Types of pollution; Importance of changing one's lifestyle; Use of eco-friendly products; Reduction in the use of cosmetics.

ABSTRACTArtemisinin-derivative combination therapies (ACT) are highly efficacious against multidrug-resistant Plasmodium falciparummalaria. Few efficacy data, however, are available for vivax malaria. With high rates of chloroquine (CQ) resistance in both vivax and falciparum malaria in Papua Province, Indonesia, new combination therapies are required for both species. We recently found artesunate plus sulfadoxine-pyrimethamine (ART-SP) to be highly effective (96%) in the treatment of falciparum malaria in Papua Province. Following a preliminary study of CQ plus sulfadoxine-pyrimethamine (CQ-SP) for the treatment of Plasmodium vivaxinfection, we used modified World Health Organization criteria to evaluate the efficacy of ART-SP for the treatment of vivax malaria in Papua. Nineteen of 22 patients treated with ART-SP could be evaluated on day 28, with no early treatment failures. Adequate clinical and parasitological responses were found by day 14 in all 20 (100%) of the patients able to be evaluated and by day 28 in 17 patients (89.5%). Fever and parasite clearance times were short, with hematological improvement observed in 70.6% of the patients. Double (at positions 58 and 117) and quadruple (at positions 57, 58, 61, and 117) mutations in the P. vivaxdihydrofolate reductase (PvDHFR) were common in Papuan P. vivaxisolates (46 and 18%, respectively). Treatment failure with SP-containing regimens was significantly higher with isolates with this PvDHFR quadruple mutation, which included a novel T→M mutation at residue 61 linked to an S→T (but not an S→N) mutation at residue 117. ART-SP ACT resulted in a high cure rate for both major Plasmodiumspecies in Papua, though progression of DHFR mutations in both species due to the continued use of SP monotherapy for clinically diagnosed malaria threatens the future utility of this combination.

We assess the global properties of associated C IV ll1548, 1550 absorption lines measured in the spectra of radio-loud quasars drawn from a near-complete, low-frequency-selected sample. The observations span rest-frame C IV in two redshift ranges, 0.7 < z < 1.0 and 1.5 < z < 3.0, which were targeted in the UV with the Hubble Space Telescope Space Telescope Imaging Spectrograph and in the optical with ground-based telescopes. First, we corroborate trends for C IV associated absorption to be found preferentially in steep-spectrum and lobe-dominated quasars, implying that the absorbing material tends to lie away from the radio-jet axis. Furthermore, we find a clear anticorrelation between C IV absorption strength and the projected linear size of steep-spectrum quasars, indicative of an evolutionary sequence. We also find that heavily absorbed quasars are systematically redder, implying that dust is mixed in with the C IV-absorbing gas. No redshift dependence was found in any of the trends considered. These new results show that radio sources are triggered in galaxies that are exceptionally rich in gas and dust, which then dissipates on a timescale comparable to but less than that of the radio source. This observational sequence, together with the lack of redshift dependence, points to a direct causal link between the event that triggered the radio source and the build-up of absorbing gas and dust, whose make-up is tantalizingly similar to the products of a postmerger starburst. Thus, these new results provide direct evidence for the clearing of absorbing material around quasars with time, as well as the probable association of starburst activity with the onset of the radio activity in active galactic nuclei.

Im folgenden Beitrag werden die Ergebnisse einer Studie zusammengefaßt, die sich mit der Evaluation der Implementation (nicht den weiteren Auswirkungen) eines Programms zur differenzierten Verfahrensdurchführung befaßt. Dieses Programm, im Januar 1994 am und vom Obersten Gericht von Neu Südwales eingeführt, wird in seiner Entwicklung und seinen Grundzügen dargestellt; es wird untersucht, inwieweit im ersten Jahr nach Erlaß seine Handhabung wie vom Gericht beabsichtigt erfolgte. Es wurde festgestellt, daß das Programm hinsichtlich seiner Vorschriften, die auf eine angemessene Fallbehandlung und eine Verkürzung der Verfahrensdauer zielen, nicht gänzlich wie geplant durchgeführt wurde. Darüber hinaus wurde festgestellt, daß das Programm in sich so angelegt ist, daß auch bei korrekter Durchführung einzelner Bestimmungen kontraproduktive Effekte entstehen können. Diese Befunde dürften nicht folgenlos sein für die künftige Realisierung der Programmziele (die selbst noch nicht Gegenstand der vorliegenden Studie ist).

Using complete samples of steep‐spectrum quasars, we present evidence for a correlation between radio and optical luminosity which is not caused by selection effects, nor caused by an orientation dependence (such as relativistic beaming), nor a by‐product of cosmic evolution. We argue that this rules out models of jet formation in which there are no parameters in common with the production of the optical continuum. This is arguably the most direct evidence to date for a close link between accretion on to a black hole and the fuelling of relativistic jets. The correlation also provides a natural explanation for the presence of aligned optical/radio structures in only the most radio‐luminous high‐redshift galaxies.

Studies that treat creativity as operant behavior were critically reviewed. Of the twenty studies, most met minimal requirements for methodological adequacy; all provided at least some evidence for increased creative responding. Major difficulties involved potential confounds between instructions and contingencies, lack of an independent record of the training interaction, lack of social validation data, and very limited evidence for generalization. Several issues were discussed: problems in the behavioral definition of creativity, objections to the use of contingent reinforcement, and the need for empirical analysis of the creative process.

This article argues for the existence of female social networks, which were centered around abbeys and which can be viewed as a female dimension to male patron-client networks. This female dimension forces some reevaluation of the nature of male patron-client networks away from the model of power structures towards a function of noble society. A study of the nuns who resided at the abbey of Saint Pierre de Reims, which was headed by a member of the Guise family, shows an expansive and interwoven network of women, both kinship and affinity, occupying the same physical space or communicating with each other. It also shows that a member of a noble family who was assigned to a church career had a valuable and significant role to play in family strategies and dynastic planning.

Joanne Baker lauds a paean to the experimentalists of the BBC Radiophonic Workshop.

ABSTRACTMalaria-specific rapid diagnostic tests (RDTs) targeting aldolase show highly variable sensitivities. We assessed diversity in Plasmodium falciparumand P. vivaxaldolases by sequencing the coding genes from parasites of various origins. The results show that aldolases are highly conserved, indicating that antigenic diversity is not a cause of variable RDT sensitivity.

Polish codebreakers paved the way for Alan Turing to decrypt German messages in the Second World War. Joanne Baker commends a gripping tale. Polish codebreakers paved the way for Alan Turing to decrypt German messages in the Second World War. Joanne Baker commends a gripping tale.