Recombinant canine distemper virus strain Snyder Hill expressing green or red fluorescent proteins causes meningoencephalitis in the ferret

The propensity of canine distemper virus (CDV) to spread to the central nervous system is one of the primary features of distemper. Therefore, we developed a reverse genetics system based on the neurovirulent Snyder Hill (SH) strain of CDV (CDV(SH)) and show that this virus rapidly circumvents the blood-brain and blood-cerebrospinal fluid (CSF) barriers to spread into the subarachnoid space to induce dramatic viral meningoencephalitis. The use of recombinant CDV(SH) (rCDV(SH)) expressing enhanced green fluorescent protein (EGFP) or red fluorescent protein (dTomato) facilitated the sensitive pathological assessment of routes of virus spread in vivo. Infection of ferrets with these viruses led to the full spectrum of clinical signs typically associated with distemper in dogs during a rapid, fatal disease course of approximately 2 weeks. Comparison with the ferret-adapted CDV(5804P) and the prototypic wild-type CDV(R252) showed that hematogenous infection of the choroid plexus is not a significant route of virus spread into the CSF. Instead, viral spread into the subarachnoid space in rCDV(SH)-infected animals was triggered by infection of vascular endothelial cells and the hematogenous spread of virus-infected leukocytes from meningeal blood vessels into the subarachnoid space. This resulted in widespread infection of cells of the pia and arachnoid mater of the leptomeninges over large areas of the cerebral hemispheres. The ability to sensitively assess the in vivo spread of a neurovirulent strain of CDV provides a novel model system to study the mechanisms of virus spread into the CSF and the pathogenesis of acute viral meningitis.

Perceived causes of prescribing errors by junior doctors in hospital inpatients:a study from the PROTECT programme

Prescribing errors are a major cause of patient safety incidents. Understanding the underlying factors is essential in developing interventions to address this problem. This study aimed to investigate the perceived causes of prescribing errors among foundation (junior) doctors in Scotland.

Aflatoxin exposure in utero causes growth faltering in Gambian infants

Background Growth faltering in West African children has previously been associated with dietary exposure to aflatoxins, particularly upon weaning. However, in animal studies in utero exposure to low levels of aflatoxin also results in growth faltering.

Objective This study investigated the effect of in utero aflatoxin exposure on infant growth in the first year of life in The Gambia.

Methods Height and weight were measured for 138 infants at birth and at regular monthly intervals for one year. Aflatoxin-albumin (AF-alb) adduct level was measured in maternal blood during pregnancy, in cord blood and in infants at age 16 weeks.

Results The geometric mean AF-alb levels were 40.4pg/mg (range 4.82-60.8pg/mg), 10.1pg/mg (range 5.01-89.6pg/mg) and 8.7pg/mg (range 5.0-30.2pg/mg) in maternal, cord and infant blood, respectively. AF-alb in maternal blood was a strong predictor of both weight (P = 0.012) and height (P = 0.044) gain, with lower gain in those with higher exposure. A reduction of maternal AF-alb from 110pg/mg to 10pg/mg would lead to a 0.8kg increase in weight and 2cm increase in height within the first year of life.

Conclusions This study shows a strong effect of maternal aflatoxin exposure during pregnancy on growth in the first year of life and thus extends earlier observations of an association between aflatoxin exposure during infancy and growth faltering. The findings imply value in targeting intervention strategies at early life exposures.

Wild-type Measles Virus Infection Upregulates Poliovirus Receptor-Related 4 and Causes Apoptosis in Brain Endothelial Cells by Induction of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand

Small numbers of brain endothelial cells (BECs) are infected in children with neurologic complications of measles virus (MV) infection. This may provide a mechanism for virus entry into the central nervous system, but the mechanisms are unclear. Both in vitro culture systems and animal models are required to elucidate events in the endothelium. We compared the ability of wild-type (WT), vaccine, and rodent-adapted MV strains to infect, replicate, and induce apoptosis in human and murine brain endothelial cells (HBECs and MBECs, respectively). Mice also were infected intracerebrally. All MV stains productively infected HBECs and induced the MV receptor PVRL4. Efficient WT MV production also occurred in MBECs. Extensive monolayer destruction associated with activated caspase 3 staining was observed in HBECs and MBECs, most markedly with WT MV. Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), but not Fas ligand, was induced by MV infection. Treatment of MBECs with supernatants from MV-infected MBEC cultures with an anti-TRAIL antibody blocked caspase 3 expression and monolayer destruction. TRAIL was also expressed in the endothelium and other cell types in infected murine brains. This is the first demonstration that infection of low numbers of BECs with WT MV allows efficient virus production, induction of TRAIL, and subsequent widespread apoptosis.

Arsenate causes differential acute toxicity to two P-deprived genotypes of rice seedlings (Oryza sativa L.)

Significant genotypic difference in response to arsenate toxicity in rice (Oryza sativa) was investigated in root elongation, arsenate uptake kinetics, physiological and biochemical response and arsenic (As) speciation. Uptake kinetics data showed that P-deprived genotype 94D-54 had a little higher As uptake than P-deprived 94D-64, but the difference was not large enough to cause acute toxicity in P-deprived 94D-54. There was no difference in tissue P concentrations between the two genotypes under P deficient conditions. In addition, arsenic speciation in plant tissues (using high performance liquid chromatography-inductively coupled plasma mass spectrometry) was not different between P pretreatments and between genotypes. P-deprived genotype 94D-54 suffered much higher stress induced by arsenate toxicity than P-deprived genotype 94D-64, in terms of lipid peroxidation, tissue H2O2 concentrations and exosmosis of K, P and As. However, P-deprived 94D-54 also had higher overproduction of enzymatic antioxidants (with higher GPX, SOD, CAT) and NPT (non-protein thiols) than P-deprived 94D-64. It appeared that, the higher sensitivity of P-deprived 94D-54 to arsenate toxicity might cause the overproduction of NPT, thus leading to the depletion of GSH and to the accumulation of H2O2. The differential sensitivity of the two genotypes has major implications for breeding rice for As affected paddy soil.

Rapid rise in Effective Sea-Level in southwest Bangladesh: Its causes and contemporary rates

Evidence is presented from three estuarine tide gauges located in the
Sundarban area of southwest Bangladesh of relative sea level rise
substantially in excess of the generally accepted rates from altimetry, as
well as previous tide-gauge analyses. It is proposed that the difference
arises from the use of relative mean sea level (RMSL) to characterise the
present and future coastal flood hazard, since RMSL can be misleading in
estuaries in which tidal range is changing. Three tide gauges, one located in
the uninhabited mangrove forested area (Sundarban) of southwest
Bangladesh, the others in the densely populated polder zone north of the
present Sundarban, show rates of increase in RMSL ranging from 2.8 mm
a-1 to 8.8 mm a-1. However, these trends in RMSL disguise the fact that high
water levels in the polder zone have been increasing at an average rate of
15.9 mm a-1 and a maximum of 17.2 mm a-1. In an area experiencing tidal
range amplification, RMSL will always underestimate the rise in high water
levels; consequently, as an alternative to RMSL, the use of trends in high
water maxima or ‘Effective Sea Level Rise’ (ESLR) is adopted as a more
strategic parameter to characterise the flooding hazard potential. The rate
of increase in ESLR is shown to be due to a combination of deltaic
subsidence, including sediment compaction, and eustatic sea level rise, but
principally as a result of increased tidal range in estuary channels recently
constricted by embankments. These increases in ESLR have been partially
offset by decreases in fresh water discharge in those estuaries connected
to the Ganges. The recognition of increases of the effective sea level in the
Bangladesh Sundarban, which are substantially greater than increases in
mean sea level, is of the utmost importance to flood management in this
low-lying and densely populated area.

Considering Just-World Thinking in Counter-Terrorism Cases: Miscarriages of Justice in Northern Ireland

Recent literature has drawn a parallel between the discriminatory application of counterterrorism legislation to the Irish population in the United Kingdom during the Northern Ireland conflict and the targeting of Muslims after September 2001. Less attention has been paid to lessons that can be drawn from judicial decision making in terrorism-related cases stemming from the Northern Ireland conflict. This Article examines Northern Ireland Court of Appeal (“NICA”) jurisprudence on miscarriages of justice in cases regarding counterterrorism offenses. In particular, the Article focuses on cases referred after the 1998 peace agreements in Northern Ireland from the Criminal Cases Review Commission (“CCRC”), a relatively new entity that investigates potential wrongful convictions in England, Wales, and Northern Ireland. Although the NICA’s human rights jurisprudence has developed significantly in recent years, the study of CCRC-referred cases finds that judges have retained confidence in the integrity of the conflict-era counterterrorism system even while acknowledging abuses and procedural irregularities that occurred. This study partially contradicts contentions that judicial deference to the executive recedes in a post-conflict or post-emergency period. Despite a high rate of quashed convictions, the NICA’s decisions suggest that it seeks to limit a large number of referrals and demonstrate a judicial predisposition to defend the justness of the past system’s laws and procedure. This perspective is consistent with what social psychologists have studied as “just-world thinking,” in which objective observers, although motivated by a concern with justice, believe—as a result of cognitive bias—that individuals “got what they deserved.” The Article considers other potential interpretations of the jurisprudence and contends that conservative decision making is particularly dangerous in the politicized realm of counterterrorism and in light of the criminalization of members of suspect communities.

Prevalence and Causes of Prescribing ErrorsL The PRescribing Outcomes for Trainee Doctors Engaged in Clinical Training (PROTECT) Study

Objectives: Study objectives were to investigate the prevalence and causes of prescribing errors amongst foundation doctors (i.e. junior doctors in their first (F1) or second (F2) year of post-graduate training), describe their knowledge and experience of prescribing errors, and explore their self-efficacy (i.e. confidence) in prescribing.

Method: A three-part mixed-methods design was used, comprising: prospective observational study; semi-structured interviews and cross-sectional survey. All doctors prescribing in eight purposively selected hospitals in Scotland participated. All foundation doctors throughout Scotland participated in the survey. The number of prescribing errors per patient, doctor, ward and hospital, perceived causes of errors and a measure of doctors’ self-efficacy were established.

Results: 4710 patient charts and 44,726 prescribed medicines were reviewed. There were 3364 errors, affecting 1700 (36.1%) charts (overall error rate: 7.5%; F1:7.4%; F2:8.6%; consultants:6.3%). Higher error rates were associated with : teaching hospitals (p,0.001), surgical (p = ,0.001) or mixed wards (0.008) rather thanmedical ward, higher patient turnover wards (p,0.001), a greater number of prescribed medicines (p,0.001) and the months December and June (p,0.001). One hundred errors were discussed in 40 interviews. Error causation was multi-factorial; work environment and team factors were particularly noted. Of 548 completed questionnaires (national response rate of 35.4%), 508 (92.7% of respondents) reported errors, most of which (328 (64.6%) did not reach the patient. Pressure from other staff, workload and interruptions were cited as the main causes of errors. Foundation year 2 doctors reported greater confidence than year 1 doctors in deciding the most appropriate medication regimen.

Conclusions: Prescribing errors are frequent and of complex causation. Foundation doctors made more errors than other doctors, but undertook the majority of prescribing, making them a key target for intervention. Contributing causes included work environment, team, task, individual and patient factors. Further work is needed to develop and assess interventions that address these.