An outbreak vector-host epidemic model with spatial structure: the 2015-2016 Zika outbreak in Rio De Janeiro.

BACKGROUND: A deterministic model is developed for the spatial spread of an epidemic disease in a geographical setting. The disease is borne by vectors to susceptible hosts through criss-cross dynamics. The model is focused on an outbreak that arises from a small number of infected hosts imported into a subregion of the geographical setting. The goal is to understand how spatial heterogeneity of the vector and host populations influences the dynamics of the outbreak, in both the geographical spread and the final size of the epidemic. METHODS: Partial differential equations are formulated to describe the spatial interaction of the hosts and vectors. The partial differential equations have reaction-diffusion terms to describe the criss-cross interactions of hosts and vectors. The partial differential equations of the model are analyzed and proven to be well-posed. A local basic reproduction number for the epidemic is analyzed. RESULTS: The epidemic outcomes of the model are correlated to the spatially dependent parameters and initial conditions of the model. The partial differential equations of the model are adapted to seasonality of the vector population, and applied to the 2015-2016 Zika seasonal outbreak in Rio de Janeiro Municipality in Brazil. CONCLUSIONS: The results for the model simulations of the 2015-2016 Zika seasonal outbreak in Rio de Janeiro Municipality indicate that the spatial distribution and final size of the epidemic at the end of the season are strongly dependent on the location and magnitude of local outbreaks at the beginning of the season. The application of the model to the Rio de Janeiro Municipality Zika 2015-2016 outbreak is limited by incompleteness of the epidemic data and by uncertainties in the parametric assumptions of the model.

Chemical composition of Acid fog.

Fog water collected at three sites in Los Angeles and Bakersfield, California, was found to have higher acidity and higher concentrations of sulfate, nitrate, and ammonium than previously observed in atmospheric water droplets. The pH of the fog water was in the range of 2.2 to 4.0. The dominant processes controlling the fog water chemistry appear to be the condensation and evaporation of water vapor on preexisting aerosol and the scavenging of gas-phase nitric acid.

A mathematical model for indirectly transmitted diseases.

We consider a mathematical model for the indirect transmission via a contaminated environment of a microparasite between two spatially distributed host populations having non-coincident spatial domains. The parasite is benign in a first population and lethal in the second one. Global existence results are given for the resulting reaction-diffusion system coupled with an ordinary differential equation. Then, invasion and persistence of the parasite are studied. A simplified model for the transmission of a hantavirus from bank vole to human populations is then analysed.

Percutaneous balloon mitral valvotomy with the Inoue single-balloon catheter: commissural morphology as a determinant of outcome.

OBJECTIVES: The aim of this study was to determine the importance to outcome and the predictability of commissural splitting in patients undergoing percutaneous mitral valvotomy with the Inoue single-balloon catheter. BACKGROUND: Echocardiographic scoring systems devised to predict mitral valvotomy outcome are based on assessment of leaflet and subvalvular morphology, but the specific importance of commissural morphology has not been examined. METHODS: In 30 consecutive patients, commissural splitting was predicted on the basis of the two-dimensional echocardiographic commissural morphology: the extent of fusion, fibrosis or calcification of each commissure. Valve morphology also was evaluated according to a previously described echocardiographic scoring system. RESULTS: Splitting of one or both commissures occurred in 24 patients (80%) and was associated with a significantly greater mean increase in valve area (85%) than if neither commissure was split (13%). A good outcome from valvotomy (defined as valve area > 1.5 cm2 and increase in valve area > 25%) was achieved in 96% of those in whom one or both commissures split, but in none of the patients in whom neither commissure split. Whether or not splitting of at least one commissure would occur was predicted accurately in 28 (93%) of the 30 patients. Consequently, the prediction that one or both commissures would split was associated with a good outcome in 23 (89%) of 26 patients, whereas the prediction that neither commissure would split was not associated with a good outcome in any patient. There was no significant difference in the increase in mitral valve area between those with a mitral echocardiographic score < 8 and those with a score > or = 8. New or worsening mitral regurgitation occurred in nine patients, most commonly as a jet directed through a split commissure. CONCLUSIONS: Commissural splitting is the dominant mechanism by which mitral valve area is increased with the Inoue balloon technique, and it can be predicted by echocardiographic assessment of commissural morphology. Commissural morphology is a better predictor of outcome than is the mitral echocardiographic score.

Effect of glyceryl trinitrate on peripheral arteries alters left ventricular hydraulic load in man.

Effects of sublingual glyceryl trinitrate (GTN) were studied in ten patients without heart failure during diagnostic cardiac catheterisation following angiography. GTN caused substantial reduction in peak left ventricular and aortic pressure (19 mmHg) with lesser reduction in mean aortic pressure (9 mmHg) and no change in diastolic aortic pressure. Reduction in stroke volume (by 15%), associated with fall in left ventricular end diastolic pressure (by 4 mmHg) was insufficient to explain the marked (17 mmHg - 34%) reduction in pulse pressure. Decrease in pulse pressure was associated with loss of the late systolic peak on both the aortic and left ventricular pressure wave. This peak is caused by pulse wave reflection. GTN caused no change in peripheral resistance or in indices of aortic compliance (characteristic impedance, total arterial compliance) but was associated with reduction in fluctuations of both modulus and phase of aortic impedance. All these changes in pressure waves and in impedance spectra are explicable on the basis of decreased peripheral wave reflection. This can be attributed to the known vasodilatory effect of GTN on the peripheral arteries. Simulation of arterial vasodilatation in a multi-branched model of the systemic arterial system confirmed this interpretation. Dilatation of peripheral arteries explains in part the beneficial effects of GTN in adult man.

Long-term results of tricuspid valve replacement and the problem of prosthetic valve thrombosis.

Observations in 71 patients having tricuspid valve replacement over a 14-year period are described. The operative mortality rate was 10% and the actuarial survival rate was 73% at 5 years and 47% at 10 years. Survival was unaffected by the number of valves replaced or the type used (27 Starr-Edwards, 32 Björk-Shiley, 8 Lillehei-Kaster, and 4 porcine xenografts). Complications were common: 3 deaths were related to anticoagulation and 1 was due to a systemic embolus. Six patients required permanent pacing. There was a very high incidence of thrombosis of the prosthetic tricuspid valve. Twenty percent of the tilting disc valves thrombosed, compared with 4% of the Starr-Edwards valves (p less than 0.05). Symptoms of thrombosis were usually insidious, and its diagnosis was often delayed. There was a continuing risk of this complication, and presentation occurred up to 12 years after the original operation. Thrombolytic therapy with streptokinase was successful in 1 of 2 patients. Replacement of the thrombosed prosthetic valves was carried out without mortality in 8 patients.

Intracoronary stenting without intravascular ultrasound guidance followed by antiplatelet therapy with aspirin alone in selected patients.

One hundred selected patients with 103 lesions were treated with the deployment of 117 Palmaz-Schatz stents without the use of intravascular ultrasound, followed by antiplatelet therapy with aspirin alone. Angiographic and clinical follow-up revealed 2 stent thromboses; 3 stents required redilation, and 3 patients required intervention for disease progression elsewhere, suggesting that this approach can be applied effectively in selected patients.

Stereo-specific cytotoxic effects of gossypol enantiomers and gossypolone in tumour cell lines.

The naturally occurring compound, gossypol, has been previously used as a male oral contraceptive, for the treatment of benign gynaecological conditions and cancer patients. Long-term daily dosing with gossypol is associated with minimal side effects and no myelosuppression. Since gossypol exhibits atropisomerism due to the restricted rotation about the 2,2' carbon bond, we have isolated the l- and d-isomers by Schiff's base formation using a chiral amine and regenerated the enantiomers by acid hydrolysis. The enantiomers and the proposed oxidative metabolite, gossypolone, were characterized by HPLC, 1H-NMR and optical rotation. The cytotoxicity was assessed in cell cultures derived from melanoma, lung, breast, cervix, and leukaemia using the MTT viability assay. The cytotoxicity of gossypolone was similar to racemic gossypol in five out of the six cell lines studied. The l-enantiomer of gossypol induced a dose-dependent cell kill in all cell lines with a mean IC50 of 20 microM and was significantly more potent than racemic gossypol, the d-enantiomer of gossypol and gossypolone. In addition, when the leukaemia line was exposed to l-gossypol (0.5-10 microM) over a 4-day period, a schedule-dependent decrease in cell viability was observed. l-Gossypol was also compared with respective drugs used to treat patients with melanoma, lung cancer and leukaemia. The data indicate that l-gossypol was significantly more active than cisplatin, melphalan and dacarbazine in the two melanoma lines, cisplatin and daunorubicin in the lung line and hydroxyurea and busulphan in the leukaemia line. Preliminary studies using one melanoma line showed that the l-isomer induced cell shrinkage, membrane blebbing and DNA fragmentation, characteristics suggestive of apoptotic cell death.

Thrombolytic therapy for a thrombosed Bjork-Shiley tricuspid valve prosthesis.

A 67-year-old mand in whom mitral and tricuspid Bjork-Shiley tilting disc prostheses had been implanted 68 months previously presented with thrombotic obstruction of his tricuspid prosthesis. Initial cardiac catheterization demonstrated a significant transprosthetic tricuspid diastolic gradient (9.5 mmHg) with a calculated prosthetic valve orifice area (0.62 cm2) indicating a critical degree of stenosis. The resting cardiac index was markedly reduced (1.5 l/m2/min). Following an intravenous infusion of streptokinase for 66 hours, repeat cardiac catheterization revealed a 50% reduction in transprosthetic diastolic gradient across the tricuspid valve (4.7 mmHg), a greater than fourfold increase in prosthetic valve orifice area (2.87 cm2) with a normal resting cardiac index (3.1 l/m2/min).

Comparison of the head and neck position of elite dressage horses during top-level competitions in 1992 versus 2008.

Among veterinary surgeons, interest has recently increased in the role of the horse's neck as a causative factor in complex locomotor disturbances. Specifically, controversy surrounds the trend for the head to be carried behind the vertical (BHV) in contravention of Fédération Equestre Internationale (FEI) rules. The aim of this study was to determine whether the head angulation of elite dressage horses has changed over the last 25 years, and whether head angulation correlates with the competition score awarded. Head angle was measured from videos recorded during the Grand Prix test at the 1992 Olympic Games and the 2008 World Cup Final, during collected canter (CC), collected trot (CT), passage (Pa), and piaffe (Pi). Head angulations were BHV in CC and CT in both 1992 and 2008. The likelihood of being BHV during Pa or Pi was significantly greater in 2008 than in 1992 (P <0.05). Higher scores correlated significantly with head positions that were further BHV during Pi in 2008 (P <0.05). Head angulations were orientated BHV in all paces in 2008, whereas in 1992 this was only the case for CT and CC. These findings support the hypothesis that, in recent years, FEI dressage judges have not penalised horses for a head position BHV. The findings also support the need for further studies of the effects of head and neck position on the health of horses.

Cilia in the human kidney.

Utilizing transmission electron microscopy we have found multiple cilia with a 9 + 2 microtubular pattern (the same type found in the bronchial tree) in the renal tubules of four adults with the nephrotic syndrome. Each patient had a different pathologic diagnosis: amyloidosis, lipoid nephrosis, membranoproliferative glomerulonephritis, and focal segmental glomerulosclerosis. Previously, multiple renal tubular cilia with 9 + 2 architecture had been reported in patients with Burnett's syndrome, systemic lupus erythematosus, and congenital nephrotic syndrome. Additionally, we found multiple cilia in the metanephric tubules of 4 of 4 human fetuses. Pathologists should be aware that cilia with various microtubular patterns occur in human adult kidneys.

Intravenous sotalol for the treatment of atrial fibrillation and flutter after cardiopulmonary bypass. Comparison with disopyramide and digoxin in a randomised trial.

The efficacy of sotalol in treating acute atrial fibrillation and flutter after open heart surgery was compared with that of a digoxin/disopyramide combination. Forty adult patients with postoperative atrial arrhythmias were randomised into either group 1 (sotalol 1 mg/kg bolus intravenously plus 0.2 mg/kg intravenously over 12 hours) or group 2 (digoxin 0.75 mg intravenously, then two hours later disopyramide 2 mg/kg intravenous bolus and 0.4 mg/kg/h intravenously for 10 hours). In each group, 17 out of 20 patients reverted to sinus or junctional rhythm within 12 hours. The time to reversion in group 1 was significantly shorter than in group 2. Systolic blood pressure fell by greater than or equal to 20 mm Hg or to less than or equal to 90 mm Hg during drug administration in 17 out of 20 patients in group 1 (sotalol withdrawn in two) and in none out of 20 in group 2. Two patients in group 1 developed transient bradycardia (sotalol withdrawn in one). None of 17 patients in group 1 and two of 17 in group 2 relapsed temporarily into atrial fibrillation during the 12 hours of intravenous treatment. On continued oral treatment, one late relapse occurred in group 1 and five in group 2, and five patients in group 2 had disopyramide withdrawn because of anticholinergic side effects (acute urinary retention in four). Sotalol was as effective as the digoxin/disopyramide combination and acted significantly faster. Sensitivity to beta blockade in these patients may be related to high plasma catecholamine concentrations known to occur after cardiopulmonary bypass.

Atheromatous coronary artery ectasia.

Of 431 consecutive patients who underwent coronary arteriography during the twelve month period ending December 1976, 23 (5%) had angiographically documented coronary artery ectasia. Of these only five had "pure" or isolated ectasia, whilst 18 had ectatic disease combined with coronary artery stenoses. Clinical findings that are significantly associated with ectasia are male predominance (96%), abnormal lipid patterns (64%), a positive family history of coronary artery disease (57%) and previous hypertension (50%). Anatomically, ectasia most often involved the right coronary artery (96%), then the circumflex artery (75%) and the left anterior descending artery (57%). Only seven (five with severe proximal stenoses) of the 28 patients had coronary artery bypass grafts. Care should be taken not to overdiagnose narrow segments between ectatic, dilated segments as being obstructions. Failure to appreciate this resulted in two patients with isolated coronary artery ectasia having bypass grafts performed with little relief of their symptoms.

Regional differences in gas trapping (airway closure) between apex and base of excised rat lungs.

Excised rat lungs were ventilated with air under three conditions: (a) while suspended by the trachea and surrounded by air, (b) while inverted and surrounded by saline, and (c) while upright and surrounded by saline. The distribution of transpulmonary pressures over which gas trapping occurred in the lung for each of the three conditions was found by a method previously described by Frazer et al. (1979). A distribution having a small standard deviation (SD) indicates more uniform gas trapping in the lung while a larger SD indicates less uniform gas trapping. Results showed that the SD was 0.63 for the inverted lung in saline, 1.10 for the lung in air, and 1.57 for the upright lung in saline. We conclude that gas trapping in lungs inverted in saline occurs more uniformly than gas trapping in lungs in air or upright in saline. The results obtained in saline in the upright and inverted position also imply that as the lung is deflated surrounded by air, gas trapping initially occurs in the base of the lung before it occurs in the apex. Since gas trapping and airway closure are related, there could also be intrinsic dissimilarities in airway closure between the apex and base of excised rat lungs suspended by the trachea in air.

Atrial tachyarrhythmias after cardiac surgery: results of disopyramide therapy.

Of 1,247 consecutive patients who underwent cardiac surgery, 297 (24%) developed a post-operative atrial tachyarrhythmia. Of these patients, 201 were suitable for treatment according to the study protocol. All patients were initially given digoxin 0.75 mg intravenously (i.v.). After two hours, those 156 patients whose atrial arrhythmias persisted were given a 2 mg/kg loading dose of disopyramide (i.v.), followed by a constant i.v. infusion (0.4 mg kg-1 h-1) or oral therapy (600 mg daily). Within a further 12 hours, 75 patients (48%) reverted to sinus rhythm, 24 within one hour. Thus 120/201 patients (60%) reverted to sinus rhythm within 14 hours of commencing therapy. Reversion rates of those patients with both atrial fibrillation and flutter (AF/AFL) were significantly lower than those with AF (p less than 0.001) or AFL (p less than 0.02) alone. A further 70 patients reverted to sinus rhythm in one to 13 (mean four) days on continued drug therapy. Elective cardioversion restored sinus rhythm in six subjects. Atrial arrhythmias persisted in five patients (2.5%) at hospital discharge. Side-effects of disopyramide were noted in 19% of patients. Urinary retention was common (11.5%). Four patients with atrial flutter developed 1:1 atrioventricular conduction with the disopyramide loading dose. One patient with atrial fibrillation developed ventricular tachycardia during injection of the loading dose of disopyramide, but was successfully cardioverted to sinus rhythm. Two further patients developed significant hypotension (less than 90 mmHg systolic). Disopyramide is effective in the treatment of post-operative atrial tachyarrhythmias, but its routine use in this situation may be associated with an unacceptably high incidence of side-effects.