Offset integrity reduces environmental risk: Using lessons from biodiversity and carbon offsetting to inform water quality offsetting in the catchments of the Great Barrier Reef.

Environmental offsetting has been developed as a mechanism to facilitate the benefits from economic development while avoiding or minimizing environmental harm. This is achieved by compensating for environmental impacts at one location by generating equivalent environmental improvements elsewhere. However, experience with biodiversity and carbon offsetting indicates it can be difficult to ensure the integrity of offsets. Under recent legislation in the catchments of the Great Barrier Reef (GBR), Australia, it is mandatory for water quality emissions from new or expanded point source development to be offset by reducing pollution elsewhere, frequently through reducing non-point source pollution (NPSP). Therefore, informed by experience with biodiversity and carbon offsetting, we summarised sources of uncertainty in NPSP reduction that would influence water quality offset integrity; estimated the maximum potential demand for water quality offsets from sewage treatment plants, the largest point source emitter of total nitrogen (TN) in the GBR catchments, between 2018 and 2050; and discussed the implications of both on the ability of offsetting to counterbalance the impact of economic development in catchments where nitrogen loads have a large influence on the health of important GBR ecosystems. The catchments surrounding the population centres of Cairns and Mackay had both a potentially high future demand for nitrogen water quality offsets and nitrogen loads with a strong influence on the health of the GBR. Consequently, any low integrity water quality offsets in these catchments could jeopardise progress toward the water quality improvements needed to ensure the continued health of the GBR. Water quality offsetting has numerous strengths as a policy instrument however substantial uncertainties remain related to environmental outcomes. Until further research can reduce these uncertainties, water quality offsets that are implemented near increased point source emissions and have a high certainty of effectiveness may provide a balance between scientific rigour and policy workability.

Risk for Heterosexual HIV Transmission Among Non-Injecting Female Partners of Injection Drug Users in Estonia.

The HIV epidemic in Estonia, as with other eastern European countries, is currently concentrated among injection drug users (IDUs). Non-IDUs who have IDU sex partners could serve as a potential bridge in an expanding epidemic. We applied HIV transmission modelling to data collected from non-IDU/IDU heterosexual couples in Kohtla-Järve, Estonia to estimate HIV risk from IDUs to their sex partners based on self-reported sexual behaviors shared by the couple. IDUs and their current main non-injecting sex partners were recruited for an interviewer-administered survey and HIV testing. Bernoulli modelling techniques were applied to estimate the risk of HIV transmission (incidence) among HIV negative non-injecting female partners of male IDUs. The estimated HIV incidence in this population of non-injecting women with only main sexual partners in the last 6 months ranged from 3.24 to 4.94 HIV seroconversions per 100 person years depending on the value used in the models for the per act transmission rate during acute stage infection. Non-IDUs who have IDU sex partners are at high risk for HIV and could serve as a potential bridge to a more generalized epidemic. Whether this might lead to an expansion of the HIV epidemic beyond core groups in Estonia or other Eastern European countries warrants closer study.

Disentangling the Impact of Point Defect Density and Carrier Localization-Enhanced Auger Recombination on Efficiency Droop in (In,Ga)N/GaN Quantum Wells.

The internal quantum efficiency of (In,Ga)N/GaN quantum wells can surpass 90% for blue-emitting structures at moderate drive current densities but decreases significantly for longer emission wavelengths and at higher excitation rates. This latter effect is known as efficiency "droop" and limits the brightness of light-emitting diodes (LEDs) based on such quantum wells. Several mechanisms have been proposed to explain efficiency droop including Auger recombination, both intrinsic and defect-assisted, carrier escape, and the saturation of localized states. However, it remains unclear which of these mechanisms is most important because it has proven difficult to reconcile theoretical calculations of droop with measurements. Here, we first present experimental photoluminescence measurements extending over three orders of magnitude of excitation for three samples grown at different temperatures that indicate that droop behavior is not dependent on the point defect density in the quantum wells studied. Second, we use an atomistic tight-binding electronic structure model to calculate localization-enhanced radiative and Auger rates and show that both the corresponding carrier density-dependent internal quantum efficiency and the carrier density decay dynamics are in excellent agreement with our experimental measurements. Moreover, we show that point defect density, Auger recombination, and the effect of the polarization field on recombination rates only limit the peak internal quantum efficiency to about 70% in the resonantly excited green-emitting quantum wells studied. This suggests that factors external to the quantum wells, such as carrier injection efficiency and homogeneity, contribute appreciably to the significantly lower peak external quantum efficiency of green LEDs.

Increased expression of ER stress- and hypoxia-associated molecules in grey matter lesions in multiple sclerosis.

BACKGROUND: The endoplasmic reticulum (ER) stress pathway may play a role in the pathogenesis multiple sclerosis (MS), and while ER stress-associated molecules have been demonstrated in white matter (WM) lesions, these have not been analysed in grey matter (GM) demyelination. OBJECTIVE: The objective was to characterise the type and frequency of GM lesions and establish expression profiles of ER stress- and hypoxia-associated markers. METHODS: Sections from 16 MS cases and 12 non-MS controls were stained for ER stress molecules (BiP and CHOP) and hypoxia-associated D110 antigen. RESULTS: Of the GM lesions analysed, 24% were type 1 (continuous between GM and WM), 22% were type 2 (entirely within GM) and the majority (54%) were type 3 (extending from pia mater). Comparison of GM lesions, MS normal-appearing grey matter (NAGM) and non-MS control tissue showed that NAGM, type 1 and type 3 lesions all had significantly increased levels of CHOP compared to controls. According to morphological and dual-labelling criteria, the majority of CHOP-positive cells were microglia. Approximately 50% of GM lesions contained D110-positive cells. CONCLUSION: These data suggest that ER stress plays an important role in GM lesion development and may be critical in activation of microglia in pre-lesional NAGM. The high number of lesions containing D110-positive cells suggests a role for hypoxic-like insult in GM lesion development.

BAOMS QOMS: findings from the pilot phase and lessons learned in the feasibility evaluation of a national quality improvement initiative.

The BAOMS QOMS pilot was developed and run in six England OMFS units between December 2019 - April 2020. The aims of this pilot project were: to evaluate feasibility of the questionnaires developed for the audit and how effective they were with regards to quality improvement, to test the processes associated with the data collection system and finally, to provide baseline data to support patient data collection without the requirement of prospective consent. The pilot included a series of six audits (oral and dentoalveolar [ODA], oncology, orthognathic, reconstruction, trauma, and skin). Data entry was clinician-led in five OMFS units and in one unit (EKHU), it was additionally supported by members of the clinical coding team. One hundred and twenty-eight REDCap account user details were issued and of these, 45 (35%) completed registration and 22 (17%) were active users who participated in the pilot data entry. Disproportionate focus on individual audits within QOMS was seen, though not all units offered the full range of service audited. Users suggest the skin and ODA audits were sufficiently clear, but improvement is required in the oncology and reconstruction questionnaire particularly. The pilot was successful in aiding the project team identify areas of weaknesses and strength in the design of the REDCap registry and implementation of the next phase of the initiative. The information and experience gained has to date enabled a successful application for section 251 approval from the HRA and progress for the next phase of national data collection.

Emergent properties of HIV risk among injection drug users in Tallinn, Estonia: synthesis of individual and neighbourhood-level factors.

OBJECTIVES: HIV/AIDS risk is embodied within multiple levels including structural and social levels. The aim of this study was to assess the effects of neighbourhood characteristics on HIV prevalence among injection drug users (IDU) residing in the area of Tallinn, Estonia in 2007. METHODS: A cross-sectional, multilevel design collecting individual-level data--a behaviour survey including data on self-reported residency and HIV antibody testing among 350 IDU and neighbourhood-level data--aggregate measures on socio-demo-economic residential characteristics from the 2000 Estonian census. Geocoding and multilevel modelling analysis was employed. RESULTS: Among the 350 IDU recruited, earlier age at first injection, fentanyl as the main injection drug, receptive syringe sharing, main income source other than legal employment and ever attended a syringe exchange programme remained significantly associated with increased odds of anti-HIV positivity in the multivariable analysis involving individual effects with no predictors at the neighbourhood level. In the multilevel model, individual (earlier at IDU initiation AOR 1.86, 95% CI 1.01 to 3.44; injecting opioids AOR 4.43, 95% CI 2.74 to 7.18; receptive syringe sharing AOR 2.51, 95% CI 1.86 to 3.37; main income source other than work AOR 2.04, 95% CI 1.32 to 3.14; ever attended a syringe exchange programme AOR 2.58, 95% CI 1.83 to 3.61) and neighbourhood level (higher unemployment rate AOR 5.95, 95% CI 2.47 to 14.31; greater residential change AOR 1.89, 95% CI 1.09 to 3.26) emerged as significant predictors of individual HIV-positive status. CONCLUSIONS: Our results indicate that both individual-level and emergent neighbourhood-level factors contribute to HIV risk among IDU and are amenable for preventive interventions.

Rayleigh anomaly-surface plasmon polariton resonances in palladium and gold subwavelength hole arrays.

Surface plasmon polaritons (SPPs) and Rayleigh anomalies (RAs) are two characteristic phenomena exhibited by periodic grating structures made of plasmonic materials. For Au subwavelength hole arrays, SPPs and RAs from opposite sides of the film can interact under certain conditions to produce highly intense, narrow spectral features called RA-SPP resonances. This paper reports how RA-SPP effects can be achieved in subwavelength hole arrays of Pd, a weak plasmonic material. Well-defined resonances are observed in measured and simulated optical transmission spectra with RASPP peaks as narrow as 45 nm (FWHM). Dispersion diagrams compiled from angle-resolved spectra show that RA-SPP resonances in Pd hole arrays shift in wavelength but do not decrease significantly in amplitude as the excitation angle is increased, in contrast with RA-SPP peaks in Au hole arrays. The apparent generality of the RA-SPP effect enables a novel route to optimize resonances in non-traditional plasmonic media.

Gene transfer into rat mesenchymal stem cells: a comparative study of viral and nonviral vectors.

Mesenchymal stem cells (MSCs) have been proposed for use in combinatorial gene and cell therapy protocols for the treatment of disease and promotion of repair. The efficacy of such a therapeutic approach depends on determination of which vectors give maximal transgene expression with minimal cell death. The study was carried out on bone-marrow derived rat MSCs, and a range of vectors was tested on the same stem cell preparation. Adenovirus, adeno-associated virus (AAV; serotypes 1, 2, 4, 5, and 6), lentivirus, and nonviral vectors were compared. Lentivirus proved to be most effective with transduction efficiencies of up to 95%, concurrent with low levels of cell toxicity. Adenovirus also proved effective, but a significant increase in cell death was seen with increasing viral titer. Rat MSCs remained refractory to transduction by all AAV serotypes, in contrast to rabbit MSCs tested at the same time. Lipofection of plasmid DNA gave moderate transfection levels but was also accompanied by cell death. Electroporative gene transfer proved ineffective at the parameters tested and resulted in high cell death. High and moderate levels of cell transduction using lentivirus vectors did not affect the ability of the cells to differentiate down the adipogenic pathway.

Secondary ion images of the rodent brain.

Sections of biologic tissue obtained from laboratory rodents are prepared and analyzed by secondary ion mass spectrometry. The intensity of phosphocholine secondary ions is used to identify anatomical features of the brain from secondary ion images and to evaluate the effectiveness of procedures developed. Secondary ion emission of phosphocholine (m/z 184), is found to be abundant and its intensity is heterogeneous. Effects of sample thickness are addressed. Correspondence between conventional optical images of stained tissue and secondary ion images shows that successive ion images may be used to produce a three-dimensional map of the brain, i.e., an atlas.

Organic ion imaging beyond the limit of static secondary ion mass spectrometry.

Secondary ion mass spectra and images were obtained from spikes of choline chloride, acetylcholine chloride, and methylphenylpyridinium iodide deposited onto specimens of porcine brain tissue. Samples were subsequently subjected to a dose of 10-keV Cs(+) sufficient to suppress secondary ion emission characteristic of the targeted analytes. Following ablation of the samples by massive glycerol clusters generated by electrohydrodynamic emission, secondary ion mass spectra and images could be obtained that reflected the identity and location of the spiked analytes. The absolute intensity of secondary ion emission that followed ablation was found to be between 30 and 100% of the intensity obtained prior to exposure to the high dose of Cs'. Not all chemical noise is removed by ablation, however, so that the signal-to-noise ratios after ablation correspond to between 10 and 85% of their values observed under conditions of low primary ion dose.

Charge compensation for imaging large insulating samples by using secondary ion tandem mass spectrometry.

A charge compensation technique has been developed for secondary ion mass spectrometry and imaging of insulating samples as large as 1 cm(2) using a triple quadrupole-based microprobe. The microprobe secondary ion extraction field is synchronized with a periodic primary Cs(+) beam to allow a sheetlike beam of 5-eV electrons to pass over the sample surface when the extraction field is zeroed. Electrons are attracted to, and neutralize, any points on the sample that have accumulated positive charge. Positive secondary ion images from Teflon®, a well-known insulator, illustrate the effectiveness of charge compensation. Locating and identifying analytes on dry filter paper by using tandem mass spectrometry are also demonstrated.

Dialysis adequacy and self-reported health status in a group of CAPD patients.

The purpose of the study was to describe in a cross sectional manner the self-reported level of health of a group of continuous ambulatory peritoneal dialysis (CAPD) patients and to establish whether any clinical or laboratory variables correlated with this measure of health. While undergoing routine baseline and 6 monthly measurements of weekly total urea over volume distribution (Kt/V) and weekly creatinine clearance (Ccr)/1.73 m2 body surface area (BSA), 57 patients voluntarily completed the Short Form 36 health status questionnaire (SF36) (a self-report, multidimensional, generic measure of health status). Weekly Kt/V was correlated with weekly Ccr (r = 0-81, p < 0.001). Thirty-one of the 57 patients were recorded as having Ccr < 65 L/week. A comparison with Australian interim normative data demonstrated that this group of CAPD patients reported lower scores on the eight physical and mental health components that are measured by the SF36 than did the general population. Patients who were most impaired in their physical functioning were more likely to be older, overweight, and to have a lower normalized protein catabolic rate (nPCR). Patients who were adequately dialyzed (Ccr > or = 65 L/week/1.73 m2) reported greater vitality than those patients recorded as having Ccr < 65 L/week/1.73 m2.

De novo SCN1A mutations in migrating partial seizures of infancy.

OBJECTIVE: To determine the genetic etiology of the severe early infantile onset syndrome of malignant migrating partial seizures of infancy (MPSI). METHODS: Fifteen unrelated children with MPSI were screened for mutations in genes associated with infantile epileptic encephalopathies: SCN1A, CDKL5, STXBP1, PCDH19, and POLG. Microarray studies were performed to identify copy number variations. RESULTS: One patient had a de novo SCN1A missense mutation p.R862G that affects the voltage sensor segment of SCN1A. A second patient had a de novo 11.06 Mb deletion of chromosome 2q24.2q31.1 encompassing more than 40 genes that included SCN1A. Screening of CDKL5 (13/15 patients), STXBP1 (13/15), PCDH19 (9/11 females), and the 3 common European mutations of POLG (11/15) was negative. Pathogenic copy number variations were not detected in 11/12 cases. CONCLUSION: Epilepsies associated with SCN1A mutations range in severity from febrile seizures to severe epileptic encephalopathies including Dravet syndrome and severe infantile multifocal epilepsy. MPSI is now the most severe SCN1A phenotype described to date. While not a common cause of MPSI, SCN1A screening should now be considered in patients with this devastating epileptic encephalopathy.

Periventricular heterotopia, mental retardation, and epilepsy associated with 5q14.3-q15 deletion.

BACKGROUND: Periventricular heterotopia (PH) is an etiologically heterogeneous disorder characterized by nodules of neurons ectopically placed along the lateral ventricles. Most affected patients have seizures and their cognitive level varies from normal to severely impaired. At present, two genes have been identified to cause PH when mutated. Mutations in FLNA (Xq28) and ARFGEF2 (20q13) are responsible for X-linked bilateral PH and a rare autosomal recessive form of PH with microcephaly. Chromosomal rearrangements involving the 1p36, 5p15, and 7q11 regions have also been reported in association with PH but the genes implicated remain unknown. Fourteen additional distinct anatomoclinical PH syndromes have been described, but no genetic insights into their causes have been gleaned. METHODS: We report the clinical and imaging features of three unrelated patients with epilepsy, mental retardation, and bilateral PH in the walls of the temporal horns of the lateral ventricles, associated with a de novo deletion of the 5q14.3-15 region. We used microarray-based comparative genomic hybridization to define the boundaries of the deletions. RESULTS: The three patients shared a common deleted region spanning 5.8 Mb and containing 14 candidate genes. CONCLUSION: We identified a new syndrome featuring bilateral periventricular heterotopia (PH), mental retardation, and epilepsy, mapping to chromosome 5q14.3-q15. This observation reinforces the extreme clinical and genetic heterogeneity of PH. Array comparative genomic hybridization is a powerful diagnostic tool for characterizing causative chromosomal rearrangements of limited size, identifying potential candidate genes for, and improving genetic counseling in, malformations of cortical development.

Increased nicotinamide nucleotide transhydrogenase levels predispose to insulin hypersecretion in a mouse strain susceptible to diabetes.

AIMS/HYPOTHESIS: Insulin hypersecretion may be an independent predictor of progression to type 2 diabetes. Identifying genes affecting insulin hypersecretion are important in understanding disease progression. We have previously shown that diabetes-susceptible DBA/2 mice congenitally display high insulin secretion. We studied this model to map and identify the gene(s) responsible for this trait. METHODS: Intravenous glucose tolerance tests followed by a genome-wide scan were performed on 171 (C57BL/6 x DBA/2) x C57BL/6 backcross mice. RESULTS: A quantitative trait locus, designated hyperinsulin production-1 (Hip1), was mapped with a logarithm of odds score of 7.7 to a region on chromosome 13. Production of congenic mice confirmed that Hip1 influenced the insulin hypersecretion trait. By studying appropriate recombinant inbred mouse strains, the Hip1 locus was further localised to a 2 Mb interval, which contained only nine genes. Expression analysis showed that the only gene differentially expressed in islets isolated from the parental strains was Nnt, which encodes the mitochondrial proton pump, nicotinamide nucleotide transhydrogenase (NNT). We also found in five mouse strains a positive correlation (r2 = 0.90, p < 0.01) between NNT activity and first-phase insulin secretion, emphasising the importance of this enzyme in beta cell function. Furthermore, of these five strains, only those with high NNT activity are known to exhibit severe diabetes after becoming obese. CONCLUSIONS/INTERPRETATION: Insulin hypersecretion is associated with increased Nnt expression. We suggest that NNT must play an important role in beta cell function and that its effect on the high insulin secretory capacity of the DBA/2 mouse may predispose beta cells of these mice to failure.

A new molecular mechanism for severe myoclonic epilepsy of infancy: exonic deletions in SCN1A.

We examined cases of severe myoclonic epilepsy of infancy (SMEI) for exon deletions or duplications within the sodium channel SCN1A gene by multiplex ligation-dependent probe amplification. Two of 13 patients (15%) who fulfilled the strict clinical definition of SMEI but without SCN1A coding or splicing mutations had exonic deletions of SCN1A.