Simple quantitative assessment of the outdoor versus indoor airborne transmission of viruses and COVID-19.

In this paper we develop a simple model of the inhaled flow rate of aerosol particles of respiratory origin i.e. that have been exhaled by other people. A connection is made between the exposure dose and the probability of developing an airborne disease. This allows a simple assessment of the outdoor versus indoor risk of contamination to be made in a variety of meteorological situations. It is shown quantitatively that for most cases, the outdoor risk is orders of magnitude less than the indoor risk and that it can become comparable only for extremely specific meteorological and topographical situations. It sheds light on various observations of COVID-19 spreading in mountain valleys with temperature inversions while at the same time other areas are much less impacted.

Insulin gene region-encoded susceptibility to type 1 diabetes is not restricted to HLA-DR4-positive individuals.

Type 1 or insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease of the insulin-producing pancreatic beta-cells which is determined by both genetic and environmental factors. The major histocompatibility complex and the insulin gene region (INS) on human chromosomes 6p and 11p, respectively, contain susceptibility genes. Using a mostly French data set, evidence for linkage of INS to IDDM was recently obtained but only in male meioses (suggesting involvement of maternal imprinting) and only in HLA-DR4-positive diabetics. In contrast, we find evidence for linkage in both male and female meioses and that the effect of the susceptibility gene(s) in the INS region is not dependent on the presence of HLA-DR4.

Parental origin of diabetes-associated HLA types in sibling pairs with type I diabetes.

Genetic susceptibility to type I diabetes is partly determined by genes located in the human leukocyte antigen (HLA) region on chromosome 6. It has been claimed that the transmission of HLA-encoded susceptibility is influenced by parental sex. Fathers are reported to transmit HLA-DR4 haplotypes more frequently to their diabetic offspring than mothers. More recently, it has been suggested that the presence of HLA-DR4 in a mother may influence susceptibility in her offspring, even when it is not inherited. We have analyzed 172 multiplex diabetic pedigrees from the U.K. and find no evidence to support an important effect of parental sex on the inheritance of HLA-encoded susceptibility. Examination of a further 110 pedigrees from the U.S. supports this finding. These results have important implications for strategies involving genetic screening for type I diabetes.

Clinical and neurophysiological studies of aldose reductase inhibitor ponalrestat in chronic symptomatic diabetic peripheral neuropathy.

Increased flux through the polyol pathway mediated by the enzyme aldose reductase may be associated with the development of diabetic neuropathy. Fifty-four diabetic patients (median age 56 yr, range 25-65 yr) with chronic neuropathic symptoms were randomly allocated to placebo or aldose reductase inhibition (300 or 600 mg ponalrestat ICI 128436) groups for 24 wk. Patients with vibration perception thresholds (VPTs) greater than 35 V at the great toe or thermal difference thresholds (TTs) greater than 10 degrees C on the dorsum of the foot were excluded from the trial. No significant changes were observed in symptoms of pain, numbness, or paresthesia between ponalrestat and placebo groups, and there were no improvements in VPT or TT at several sites. Posterior tibial nerve conduction velocity changed from 35.3 +/- 4.9 m/s at baseline to 33.4 +/- 4.0 m/s at 24 wk (NS) with placebo compared with 37.6 +/- 5.6 vs. 37.2 +/- 8.7 m/s (NS) with 300 mg ponalrestat and 34.5 +/- 6.1 vs. 36.2 +/- 6.8 m/s (NS) with 600 mg ponalrestat. Further studies are indicated with intervention at an earlier stage in the evolution of neuropathy and for longer periods.

Development of a pulsed uniform supersonic gas expansion system based on an aerodynamic chopper for gas phase reaction kinetic studies at ultra-low temperatures.

A detailed description of a new pulsed supersonic uniform gas expansion system is presented together with the experimental validation of the setup by applying the CRESU (French acronym for Cinétique de Réaction en Ecoulement Supersonique Uniforme or Reaction Kinetics in a Uniform Supersonic Flow) technique to the gas-phase reaction of OH radicals with 1-butene at ca. 23 K and 0.63 millibars of helium (carrier gas). The carrier gas flow, containing negligible mixing ratios of OH-precursor and 1-butene, is expanded from a high pressure reservoir (337 millibars) to a low pressure region (0.63 millibars) through a convergent-divergent nozzle (Laval type). The novelty of this experimental setup is that the uniform supersonic flow is pulsed by means of a Teflon-coated aerodynamic chopper provided with two symmetrical apertures. Under these operational conditions, the designed Laval nozzle achieves a temperature of (22.4 ± 1.4) K in the gas jet. The spatial characterization of the temperature and the total gas density within the pulsed uniform supersonic flow has also been performed by both aerodynamical and spectroscopic methods. The gas consumption with this technique is considerably reduced with respect to a continuous CRESU system. The kinetics of the OH+1-butene reaction was investigated by the pulsed laser photolysis/laser induced fluorescence technique. The rotation speed of the disk is temporally synchronized with the exit of the photolysis and the probe lasers. The rate coefficient (k(OH)) for the reaction under investigation was then obtained and compared with the only available data at this temperature.

Evidence for transhemispheric diaschisis in unilateral stroke.

Nineteen patients with strictly unilateral ischemic stroke as determined by clinical examination, computed tomography, magnetic resonance imaging, and standard angiography underwent cerebral blood flow (CBF) analysis using fluorine 18 fluoromethane and positron emission tomography. Mean flow values for averaged hemispheric, infarct, and homologous contralateral regions of interest (ROIs) were determined. All patient CBF values were significantly below comparable CBF ROIs in neurologically normal controls using Wilcoxon's two-sample rank testing. Multiple regression analysis disclosed a significant correlation between contralateral CBF are both localized CBF in the infarct ROI and patient age. Correlations between contralateral CBF and dependency score or severity of neurologic deficit at time of positron emission tomography, expired PCO2, mean arterial blood pressure, serum glucose or hematocrit, risk factor score, and number of days studied after stroke were not statistically significant. Although we did not identify the biologic mechanisms involved, we conclude that CBF reduction contralateral to a strictly unilateral ischemic infarction is due to a combination of aging and transhemispheric diaschisis.

Cerebral vasocapacitance and TIAs.

We report the vasocapacitance of the cerebral circulation, as determined by cerebral blood flow reactivity to induced hypercapnia using fluoromethane positron emission tomography, in 32 patients with unilateral anterior circulation transient ischemic attacks. A hemodynamic subset of eight patients, defined based on exertional, positional, orthostatic, or cardiac dysrhythmic induction of symptomatology, is characterized by multiple (median, 4.5 attacks per patient), brief (median, 2.5 minutes per attack), continued episodes of hemispheric ischemia including focal limb shaking. Symptomatic middle cerebral artery flow territories show significantly lower (p less than 0.04) and more asymmetric (p = 0.036) vasodilatory responses in the hemodynamic subset. Although ipsilateral internal carotid artery occlusion is more prevalent in the hemodynamic subset, the features of age, mean arterial blood pressure, carbon dioxide values, serum glucose, serum hematocrit, and number or type of risk factors do not differ significantly between groups. These studies of vasocapacitance help validate clinical criteria for cerebral hemodynamic events with an objective physiologic measurement.

Estimation of absolute left ventricular volume from gated radionuclide ventriculograms. A method using phase image assisted automated edge detection and two-dimensional echocardiography.

Twenty-four patients underwent gated cardiac blood pool (GBP) imaging, two-dimensional echocardiography (2-D echo), and single-plane contrast ventriculography (within 24 hours). Variable left ventricular (LV) regions of interest on GBP images were identified by an automated threshold radial search. To avoid excluding LV counts we indexed the search threshold to the threshold identified by a phase image generated by Fourier analysis. LV depth calculated by 2-D echo was used for attenuation correction of LV counts. LV end-diastolic volume (EDV) and end-systolic volume (ESV) were calculated by dividing attenuation, background and deadtime corrected LV count rates by the background corrected count rate/ml of venous blood drawn during the study. Correlations between radionuclide and contrast volumes were good (EDV + ESV r = 0.97, EDV r = 0.94, ESV r = 0.95). Regression lines were close to the lines of identity. This method, in which GBP imaging and automated LV edge finding are complemented by 2-D echo for count attenuation correction, demonstrated reliable and reproducible noninvasive estimates of absolute LV volume.

Is candidiasis the true cause of vulvovaginal irritation in women with diabetes mellitus?

Vulvovaginitis is common in diabetic women and is often treated with antifungal agents on the assumption that the causative organism is Candida albicans. In a survey of 100 consecutive diabetic women attending a diabetes clinic 36 had complained to their general practitioner about vulvovaginal irritation during the past three years and 26 were treated with antifungal agents without a vaginal examination or swabs being taken. In a separate study 27 post-menopausal women with non-insulin dependent diabetes and symptoms of vulvovaginitis were investigated. The organisms cultured were: Candida albicans (n = 6), beta haemolytic streptococci (n = 14), Gardnerella vaginalis (n = 2), Staphylococcus aureus (n = 2), Streptococcus milleri (n = 1), Streptococcus faecalis (n = 1), Klebsiella oxytoca (n = 1), no organisms (n = 3). Where a bacterial organism was isolated symptoms resolved in all but one case with appropriate antibiotic treatment. It is recommended that the practice of initiating antifungal treatment without taking high vaginal swabs should be reviewed and treatment should be given specifically rather than empirically.

Placebo-controlled trial of lisinopril in normotensive diabetic patients with incipient nephropathy.

To study the effects of an angiotensin converting enzyme inhibitor, lisinopril, on renal function in incipient diabetic nephropathy, a prospective double-blind randomised placebo-controlled single centre study was set up at our outpatient diabetic-renal clinic. There were 27 patients with Type I and Type II diabetes with an albumin excretion rate of between 20 micrograms/min and 200 micrograms/min, respectively and no hypertension. Intervention treatment with placebo or low dose lisinopril was for 48 weeks. The main outcome changes were in urinary albumin excretion rate, urinary prostaglandin excretion, and glomerular filtration rate. Secondary outcome measures included changes in BP and heart rate. Of the 32 patients entered into the study, 27 completed 48 weeks treatment (12 lisinopril, 15 placebo). Mean (+/- SD) urinary albumin excretion rate fell from 57.6 (25.7) micrograms/min (n = 15) at visit 1 to 26.8 (26.7) micrograms/min (n = 12) at visit 7 after 48 weeks treatment in the lisinopril group but not in the placebo group: 119.2 (116.6) micrograms/min (n = 17) vs. 113.7 (77.0) micrograms/min (n = 15). There was a least squares mean treatment difference of -67.6 micrograms/min (95% confidence interval (CI), -115.0 to -20.2, P < 0.01) in favour of lisinopril compared with placebo. After 48 weeks treatment seven lisinopril treated patients were normoalbuminuric and five were microproteinuric; three placebo treated patients were normoalbuminuric, nine were microalbuminuric and three were macroproteinuric. Excretion of prostaglandin-F1 alpha (PGF1 alpha) and thromboxane-B2 (TXB2) fell in the lisinopril treated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of the effects of an angiotensin converting enzyme inhibitor and a calcium antagonist in hypertensive, macroproteinuric diabetic patients: a randomised double-blind study.

The objective of this study was to compare the effects of an angiotensin converting enzyme inhibitor, lisinopril, with those of a calcium blocker, nifedipine, on BP control and renal function, in a prospective randomised double-blind, double-dummy trial lasting 19 weeks in patients with diabetic nephropathy. We enrolled 28 diabetic patients with hypertension and macroproteinuria from the out-patient diabetic-renal clinic. The antihypertensive treatment consisted of lisinopril or nifedipine, and their effect on arterial BP, urinary albumin excretion, glomerular filtration rate, and renal blood flow were measured. BPs at entry were 166/99 (SD 23/9) mmHg for the lisinopril group and 165/99(21/7) mmHg for the nifedipine group. BPs fell to 143/88 (17/13) mmHg for the lisinopril group and 148/85(25/10) mmHg for the nifedipine group at the end of the study. The albumin excretion rate fell in the lisinopril group from 738.7 (635.2) micrograms/min to 644.6 (965.2) micrograms/min and rose in the nifedipine group from 981.2 (1022.2) micrograms/min to 1072.5 (908.5) micrograms/min (P = NS). Glomerular filtration rates fell from 105.2 (57.5) ml/min per 1.73 m2 to 72.1 (39.4) ml/min per 1.73 m2 in the lisinopril group and from 109.9 (50.0) ml/min per 1.73 m2 to 82.9 (53.9) ml/min per 1.73 m2 in the nifedipine treated group. Renal blood flow fell from 446.8 (217.9) ml/min per 1.73 m2 to 435.1 (243.3) ml/min per 1.73 m2 for the lisinopril group and from 473.0 (216.4) ml/min per 1.73 m2 to 419.0 (278.6) ml/min per 1.73 m2 for the nifedipine group. Differences between the groups were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Techniques for the study of reaction kinetics at low temperatures: application to the atmospheric chemistry of Titan.

Data on the low-temperature (< 200 K) dependence of the kinetics of chemical reactions are of great importance for understanding the composition of planetary atmospheres (as well as interstellar clouds). To date such studies have been relatively rare but the situation is beginning to change. During the past 10 years a number of experimental instruments have been designed to address this problem. These instruments rely on either cryogenic or supersonic cooling, and both methods have been applied to the study of neutral-neutral or ion-neutral reactions. We briefly review these different techniques, with an emphasis on the CRESU method, and provide examples of the types of reactive systems that have been studied, with particular attention to those relevant to the atmosphere of Titan. The perspectives for future work are also evoked.

ApoE genotype and Alzheimer's disease in adults with Down syndrome: meta-analysis.

The apoE gene polymorphism was examined in 100 adults with Down syndrome (with and without dementia) compared to 346 control subjects without mental retardation. Meta-analysis of available data (480 subjects) revealed that apolipoprotein E genotype distribution for people with Down syndrome was similar to that of the nonretarded population. Although no significant association between possession of the apoE epsilon 4 allele and onset of Alzheimer's disease was found, subjects with the allele had a tendency towards lower age of onset of dementia. Subjects with apoE epsilon 2 allele may not develop dementia and may have increased longevity.

Noninvasive testing of cerebral perfusion reserve prior to coronary artery bypass graft surgery.

Cerebral perfusion reserve testing using fluorine-18-fluoromethane and positron emission tomographic brain scanning to define cerebral blood flow abnormalities was performed in 5 patients being considered for combined coronary and carotid reconstructive surgery. Blood flow testing during normocapnia and following hypercapnia was utilized in these patients to determine the hemodynamic significance of known extracranial carotid artery occlusive lesions. Reserve diminution in 2 of these patients prompted combined surgery, whereas normal reserve values in the other 3 prompted coronary surgery alone. Results obtained in this preliminary series show how preoperative noninvasive testing of cerebral perfusion reserve adds to the diagnostic evaluation of patients with widespread vascular disease.

Recombination of polycyclic aromatic hydrocarbon photoions with electrons in a flowing afterglow plasma.

A new technique, flowing afterglow with photoions (FIAPI), has been developed to measure the rate coefficient for the recombination of complex ions, and, in particular, polycyclic aromatic hydrocarbon (PAH) cations with electrons. The method is based on the flowing afterglow Langmuir probe - mass spectrometer apparatus at the University of Rennes I. A helium plasma is generated by a microwave discharge in a He buffer gas and downstream, a small amount of argon gas is injected to destroy any helium metastables. A very small amount of neutral PAH molecules is added to the afterglow plasma by evaporation from a plate coated with the PAH to be studied. PAH ions are then produced by photoionization of the parent molecule using a pulsed UV laser (157 nm). The laser beam is oriented along the flow tube and so a constant spatial concentration of photoions is obtained. The electron concentration along the flow tube is measured by means of a movable Langmuir probe. Ion concentration decay in time is measured at a fixed position using a quadrupole mass spectrometer which is triggered by the laser pulse. The recombination of anthracene and pyrene cations has been studied using this technique and we have found a recombination rate of (2.4 +/- 0.8) x 10(-6) cm(3) s(-1) for anthracene and (4.1 +/- 1.2) x 10(-6) cm(3) s(-1) for pyrene.

The reaction of anthracene with OH radicals: an experimental study of the kinetics between 58 and 470 K.

The first direct measurement of the reaction rate constant of a polycyclic aromatic hydrocarbon in the gas phase in the temperature range 58-470 K is reported. The reaction is OH+ anthracene and the experiment has been performed in a continuous flow Cinetique de Reaction en Ecoulement Supersonique Uniforme apparatus, which had to be modified for this purpose. Pulsed laser photolysis of H(2)O(2) has been used to generate OH radicals and laser-induced fluorescence to observe the kinetic decay of the radicals and hence determine the rate coefficients. The reaction is found to be fast, and the rate constant increases monotonically as the temperature is lowered. The rate coefficients match the expression k(cm(3) molecules(-1) s(-1))=1.12 x 10(-10)(T/300)(-0.46).

Pre-conception counselling in Asian women with non insulin dependent diabetes and impaired glucose tolerance.

Asian patients comprise greater than 8% of our diabetic clinic. Retrospective analysis of the case notes of 22 Asian patients and 20 white patients with NIDDM or impaired glucose tolerance (IGT) attending our combined diabetic/antenatal clinic during 1985-1987 confirmed the reported advantages of pre-conception counselling. Those Asian patients with NIDDM or IGT had higher corrected birthweight than a parity matched Asian control group (3,472.3 +/- 595 g v 2,798.6 +/- 672.3 g p less than 0.001). Those Asian patients who had preconception counselling had, however, significantly smaller babies (3,270.8 +/- 445.1 g v 3,714.4 +/- 727.1 g p less than 0.05). An increase in foetal and maternal complications has been documented in cases of gestational diabetes, but the glucose levels that predict an increased risk have not been clearly defined. In the Asian patients with NIDDM/IGT there was one neonatal death and two congenital abnormalities, although these mothers did not have significantly higher glycosylated haemoglobin levels. HbA1 was not a good diagnostic test for glucose tolerance. Subjects with any degree of glucose intolerance should be managed as carefully as established diabetics and preconception counselling for high risk groups may be beneficial.

Reaction kinetics at very low temperatures: laboratory studies and interstellar chemistry.

Studies of gas-phase processes at temperatures down to 10 K have recently blossomed, largely through application of the CRESU (cinétique de réaction en ecoulement supersonique uniforme) technique. The results are of considerable relevance to the synthesis of molecules in dense interstellar clouds, demonstrating that the models developed to explain the observed molecular abundances must be expanded to include reactions between electrically neutral species. In addition, the experimental results have stimulated theoretical efforts to describe the factors that control the rates of such low-temperature reactions. In this Account, the CRESU method is described and the relevance of the results discussed.