Measuring cough-related quality of life and cough frequency in pulmonary TB.

BACKGROUND: Cough is the key symptom of pulmonary TB (PTB) and is associated with transmission. No tool for measuring the subjective impact of cough in PTB has been previously validated. We sought to measure patientreported cough in PTB and investigate any relationship to objectively quantified daily cough frequency.METHODS: The validity of the Leicester Cough Questionnaire (LCQ) was assessed in sequential patients newly diagnosed with PTB at a UK hospital. Resulting LCQ scores were compared to non-cough clinical variables, and to 24-h, ambulatory, objective cough frequency measured using the Leicester Cough Monitor.RESULTS: The LCQ in 30 patients with PTB was acceptable to users and had high internal reliability (Cronbach's α = 0.93), concurrent validity (correlation with visual analogue scale for cough severity, Spearman's ρ = ???0.69) and responsiveness (substantial median increase score after 2 weeks of TB treatment: 5.1 points, IQR 1.8???9.7; P = 0.003). There was only moderate correlation between patient-reported cough and objectively-measured 24-h cough frequency in PTB (ρ = ???0.48, P = 0.008).CONCLUSION: The LCQ is valid for use in PTB, with applications that include monitoring treatment of the disease. However, there was a mismatch between objective and subjective assessment of cough, which has important implications for delayed diagnosis and transmissibility.

Estimating the aquatic risk from exposure to up to twenty-two pesticide active ingredients in waterways discharging to the Great Barrier Reef.

Pesticides decrease the quality of water reaching the Great Barrier Reef (GBR), Australia. Up to 86 pesticide active ingredients (PAIs) were monitored between July 2015 to end of June 2018 at 28 sites in waterways that discharge to the GBR. Twenty-two frequently detected PAIs were selected to calculate their combined risk when they co-occur in water samples. Species sensitivity distributions (SSDs) for the 22 PAIs to fresh and marine species were developed. The SSDs, the multi-substance potentially affected fraction (msPAF) method, Independent Action model of joint toxicity and a Multiple Imputation method were combined to convert measured PAI concentration data to estimates of the Total Pesticide Risk for the 22 PAIs (TPR22) expressed as the average percentage of species affected during the wet season (i.e., 182 days). The TPR22 and percent contribution of active ingredients of Photosystem II inhibiting herbicides, Other Herbicides, and Insecticides to the TPR22 were estimated. The TPR22 ranged from <1 % to 42 % of aquatic species being affected. Approximately 85 % of the TPR22 estimates were >1 % - meaning they did not meet the Reef 2050 Water Quality Improvement Plan's pesticide target for waters entering the GBR. There were marked spatial differences in TPR22 estimates - regions dominated by grazing had lower estimates while those with sugar cane tended to have higher estimates. On average, active ingredients of PSII herbicides contributed 39 % of the TPR22, the active ingredients of Other Herbicides contributed ~36 % and of Insecticides contributed ~24 %. Nine PAIs (diuron, imidacloprid, metolachlor, atrazine, MCPA, imazapic, metsulfuron, triclopyr and ametryn) were responsible for >97 % of TPR22 across all the monitored waterways.

Analysis of pesticide mixtures discharged to the lagoon of the Great Barrier Reef, Australia.

Organisms and ecosystems are generally exposed to mixtures of chemicals rather than to individual chemicals, but there have been relatively few detailed analyses of the mixtures of pesticides that occur in surface waters. This study examined over 2600 water samples, analysed for between 21 and 47 pesticides, from 15 waterways that discharge to the lagoon of the Great Barrier Reef in Queensland, Australia between July 1, 2011 and June 30, 2015. Essentially all the samples (99.8%) contained detectable concentrations (>limit of detection) of pesticides and pesticide mixtures. Approximately, 10% of the samples contained no quantifiable (>limit of reporting) pesticides, 10% contained one quantifiable pesticide and 80% contained quantifiable mixtures of 2-20 pesticides. Approximately 82% of samples that contained quantifiable mixtures had more than two modes of action (MoAs), but only approximately 6% had five or more MoAs. The mode, average and median number of quantifiable pesticides in all the samples were 2, 5.1 and 4, respectively. The most commonly detected compounds both individually and in mixtures were the pesticides atrazine, diuron, imidacloprid, hexazinone, 2,4-D, and the degradation product desethylatrazine. The number of pesticides and modes of action of pesticides in mixtures differed spatially and were affected by land use. Waterways draining catchments where sugar cane was a major land use had mixtures with the most pesticides.

The architecture of the Gram-positive bacterial cell wall.

The primary structural component of the bacterial cell wall is peptidoglycan, which is essential for viability and the synthesis of which is the target for crucial antibiotics1,2. Peptidoglycan is a single macromolecule made of glycan chains crosslinked by peptide side branches that surrounds the cell, acting as a constraint to internal turgor1,3. In Gram-positive bacteria, peptidoglycan is tens of nanometres thick, generally portrayed as a homogeneous structure that provides mechanical strength4-6. Here we applied atomic force microscopy7-12 to interrogate the morphologically distinct Staphylococcus aureus and Bacillus subtilis species, using live cells and purified peptidoglycan. The mature surface of live cells is characterized by a landscape of large (up to 60 nm in diameter), deep (up to 23 nm) pores constituting a disordered gel of peptidoglycan. The inner peptidoglycan surface, consisting of more nascent material, is much denser, with glycan strand spacing typically less than 7 nm. The inner surface architecture is location dependent; the cylinder of B. subtilis has dense circumferential orientation, while in S. aureus and division septa for both species, peptidoglycan is dense but randomly oriented. Revealing the molecular architecture of the cell envelope frames our understanding of its mechanical properties and role as the environmental interface13,14, providing information complementary to traditional structural biology approaches.

Does Increasing Packing Density Using Larger Caliber Coils Improve Angiographic Results of Embolization of Intracranial Aneurysms at 1 Year: A Randomized Trial.

BACKGROUND AND PURPOSE: The impact of increased aneurysm packing density on angiographic outcomes has not been studied in a randomized trial. We sought to determine the potential for larger caliber coils to achieve higher packing densities and to improve the angiographic results of embolization of intracranial aneurysms at 1 year. MATERIALS AND METHODS: Does Embolization with Larger Coils Lead to Better Treatment of Aneurysms (DELTA) was an investigator-initiated multicenter prospective, parallel, randomized, controlled clinical trial. Patients had 4- to 12-mm unruptured aneurysms. Treatment allocation to either 15- (experimental) or 10-caliber coils (control group) was randomized 1:1 using a Web-based platform. The primary efficacy outcome was a major recurrence or a residual aneurysm at follow-up angiography at 12 ± 2 months adjudicated by an independent core lab blinded to the treatment allocation. Secondary outcomes included indices of treatment success and standard safety outcomes. Recruitment of 564 patients was judged necessary to show a decrease in poor outcomes from 33% to 20% with 15-caliber coils. RESULTS: Funding was interrupted and the trial was stopped after 210 patients were recruited between November 2013 and June 2017. On an intent-to-treat analysis, the primary outcome was reached in 37 patients allocated to 15-caliber coils and 36 patients allocated to 10-caliber coils (OR = 0.931; 95% CI, 0.528-1.644; P = .885). Safety and other clinical outcomes were similar. The 15-caliber coil group had a higher mean packing density (37.0% versus 26.9%, P = .0001). Packing density had no effect on the primary outcome when adjusted for initial angiographic results (OR = 1.001; 95% CI, 0.981-1.022; P = .879). CONCLUSIONS: Coiling of aneurysms randomized to 15-caliber coils achieved higher packing densities compared with 10-caliber coils, but this had no impact on the angiographic outcomes at 1 year, which were primarily driven by aneurysm size and initial angiographic results.

Daily cough frequency in tuberculosis and association with household infection.

SETTING: Although cough in tuberculosis (TB) is presumed to be important for transmission, there is little objective supporting evidence. OBJECTIVE: To describe 24-h cough frequency in a group with TB, and investigate associations with household rates of infection. DESIGN: Patients with a new diagnosis of pulmonary TB underwent 24-h cough frequency measurement at or just before initiation of anti-tuberculosis treatment. A group with latent Mycobacterium tuberculosis infection (LTBI) acted as controls. Rates of infection among household contacts of sputum smear-positive TB were measured using the interferon-gamma release assay and the tuberculin skin test, and compared with variables relating to the contacts themselves, and to the index case, including cough frequency. RESULTS: Daily cough frequency in TB patients (n = 44) was variable (geometric mean [GM] 174, interquartile range [IQR] 68-475 coughs/24 h), higher than in LTBI (n = 17; GM 19 coughs/24 h, IQR 8-53; P < 0.001), and higher during the day than overnight (GM 8.9 coughs/h, IQR 4.1-19.0 vs. GM 2.9 coughs/h, IQR 0.7-13.4; P < 0.0001). Also, 24-h cough frequency in TB was associated with sputum smear status (P = 0.040), but not smoking (P = 0.475). Multivariable logistic regression confirmed that infection in contacts was independently associated with index case sputum smear grade (P = 0.014) and cough frequency (P = 0.022). CONCLUSION: Measurement of 24-h cough frequency in pulmonary TB helps predict infectiousness and transmission patterns.

An Update on the Adjunctive Neurovascular Support of Wide-Neck Aneurysm Embolization and Reconstruction Trial: 1-Year Safety and Angiographic Results.

BACKGROUND AND PURPOSE: The safety and efficacy of the PulseRider for the treatment of wide-neck, bifurcation aneurysms at the basilar and carotid terminus locations were studied in a prospective trial, the Adjunctive Neurovascular Support of Wide-Neck Aneurysm Embolization and Reconstruction (ANSWER) trial, reporting on initial 6-month angiographic and clinical results. This report provides insight into the longer term durability and safety with 12-month data. MATERIALS AND METHODS: Aneurysms treated with the PulseRider among enrolled sites were prospectively studied. Updated 12-month data on clinical and imaging end points are included. RESULTS: Thirty-four patients were enrolled (29 women, 5 men) with a mean age of 60.9 years. The mean aneurysm height ranged from 2.4 to 15.9 mm with a mean neck size of 5.2 mm (range, 2.3-11.6 mm). At 1 year, there were no device migrations or symptomatic in-stent stenoses. Raymond-Roy I occlusion was achieved in 53% of cases at the time of treatment and progressed to 61% and 67% at 6 and 12 months, respectively. Adequate occlusion (Raymond-Roy I/II) progressed from 88% at 6 months to 90% at 12 months. No recanalizations were observed. There was 1 delayed ischemic event. Good outcome (mRS 0-2) was achieved in 90% of patients. CONCLUSIONS: The updated 1-year results from the ANSWER trial demonstrate aneurysm stability and an acceptable safety profile for aneurysms treated at the basilar apex and carotid terminus. Prospective data from a larger set of aneurysms treated at other locations are required to assess how treatment with PulseRider compares with alternatives for treating wide-neck bifurcation aneurysms.

Hydrogel versus Bare Platinum Coils in Patients with Large or Recurrent Aneurysms Prone to Recurrence after Endovascular Treatment: A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Some patients are at high risk of aneurysm recurrence after endovascular treatment: patients with large aneurysms (Patients Prone to Recurrence After Endovascular Treatment PRET-1) or with aneurysms that have previously recurred after coiling (PRET-2). We aimed to establish whether the use of hydrogel coils improved efficacy outcomes compared with bare platinum coils. MATERIALS AND METHODS: PRET was an investigator-led, pragmatic, multicenter, parallel, randomized (1:1) trial. Randomized allocation was performed separately for patients in PRET-1 and PRET-2, by using a Web-based platform ensuring concealed allocation. The primary outcome was a composite of a residual/recurrent aneurysm, adjudicated by a blinded core laboratory, or retreatment, intracranial bleeding, or mass effect during the 18-month follow-up. Secondary outcomes included adverse events, mortality, and morbidity (mRS > 2). The hypothesis was that hydrogel would decrease the primary outcome from 50% to 30% at 18 months, necessitating 125 patients per group (500 for PRET-1 and PRET-2). RESULTS: The trial was stopped once 250 patients in PRET-1 and 197 in PRET-2 had been recruited because of slow accrual. A poor primary outcome occurred in 44.4% (95% CI, 35.5%-53.2%) of those in PRET-1 allocated to platinum compared with 52.5% (95% CI, 43.4%-61.6%) of patients allocated to hydrogel (OR, 1.387; 95% CI, 0.838-2.295; P = .20) and in 49.0% (95% CI, 38.8%-59.1%) in PRET-2 allocated to platinum compared with 42.1% (95% CI, 32.0%-52.2%) allocated to hydrogel (OR, 0.959; 95% CI, 0.428-1.342; P = .34). Adverse events and morbidity were similar. There were 3.6% deaths (1.4% platinum, 5.9% hydrogel; P = .011). CONCLUSIONS: Coiling of large and recurrent aneurysms is safe but often poorly effective according to angiographic results. Hydrogel coiling was not shown to be better than platinum.

Patients prone to recurrence after endovascular treatment: periprocedural results of the PRET randomized trial on large and recurrent aneurysms.

BACKGROUND AND PURPOSE: Some patients with large or recurrent aneurysms may be at increased risk of recurrence postcoiling. The Patients Prone to Recurrence after Endovascular Treatment (PRET) trial was designed to assess whether hydrogel coils were superior to platinum coils in these high-risk patients. This article reports periprocedural safety and operator-assessed angiographic results from the PRET trial. MATERIALS AND METHODS: PRET was a pragmatic, multicenter, randomized controlled trial. Patients had ≥10-mm aneurysms (PRET-1) or a major recurrence after coiling of an aneurysm of any size (PRET-2). Patients were randomly allocated to hydrogel or control arms (any platinum coil) by using concealed allocation with minimization. Assist devices could be used as clinically required. Aneurysms could be unruptured or recently ruptured. Analyses were on an intent-to-treat basis. RESULTS: Four hundred forty-seven patients were recruited (250 PRET-1; 197 PRET-2). Aneurysms were recently ruptured in 29% of PRET-1 and 4% of PRET-2 patients. Aneurysms were ≥10 mm in all PRET-1 and in 50% of PRET-2 patients. They were wide-neck (≥4 mm) in 70% and in the posterior circulation in 24% of patients. Stents were used in 28% of patients (35% in PRET-2). Coiling was successful in 98%. Adverse events occurred in 28 patients with hydrogel and 23 with platinum coils. Mortality (n=2, unrelated to treatment) and morbidity (defined as mRS>2 at 1 month) occurred in 25 patients (5.6%; 12 hydrogel, 13 platinum), related to treatment in 10 (4 hydrogel; 6 platinum) (or 2.3% of 444 treated patients). No difference was seen between hydrogel and platinum for any of the indices used to assess safety up to at least 30 days after treatment. At 1 month, 95% of patients were home with a good outcome (mRS≤2 or unchanged). Operator-assessed angiographic outcomes were satisfactory (complete occlusion or residual neck) in 339 of 447 or 76.4% of patients, with no significant difference between groups. CONCLUSIONS: Endovascular treatment of large and recurrent aneurysms can be performed safely with platinum or hydrogel coils.

Improvement of the pore trapping method to immobilize vital coccoid bacteria for high-resolution AFM: a study of Staphylococcus aureus.

Preparation of vital bacteria for atomic force microscope study under aqueous fluid, such as physiological buffer or bacterial growth medium, presents challenges as cells will often desorb from the supporting surface or be dislodged by the atomic force microscope tip during imaging. An established method of immobilizing coccoid bacteria is to trap cells in polycarbonate track etched filter pores. We have significantly improved this method by modifying the pore diameter of commercially available filters to correspond to the diameter of the target strain, enabling high-resolution imaging of stationary organisms under buffer and dividing organisms under growth media.

Delayed migration of a self-expanding intracranial microstent.

A 43-year-old patient with a basilar apex aneurysm had a 4.5-mm x 14-mm Enterprise stent placed from the midbasilar artery to the left P1 segment of the posterior cerebral artery. The patient experienced vertigo 4 months after stent placement and 1 week after stopping clopidogrel. At 5 months postembolization, angiography showed stent migration into the proximal basilar artery. This is the first described case of the spontaneous delayed migration of a self-expanding intracranial microstent.

Marginal sinus arteriovenous fistulas mimicking carotid cavernous fistulas: diagnostic and therapeutic considerations.

Marginal sinus fistulas (MSFs) are uncommon vascular anomalies. Occasionally, the dominant venous drainage is forced retrograde up the inferior petrosal sinus and into the cavernous sinus, causing chemosis, proptosis, and ocular hypertension, mimicking a carotid cavernous fistula. This atypical clinical presentation may lead to misdiagnosis and inappropriate hazardous treatment of an MSF. Identifying the site of the fistula and understanding the anatomy of the venous drainage are critical in providing appropriate, safe, and efficacious endovascular treatment.

Commissioning laboratory services.

Scientists often develop techniques that have obvious benefits for patients but then find great difficulty in introducing them into the National Health Service-usually because the necessary finance does not seem to be available. This article provides a practical guide.

Localized dual-wavelength fiber-optic polarimeter for the measurement of structural strain and orientation.

A single-ended, all-fiber polarimetric strain sensor with wide dynamic range and linearized response is described. Linear response is achieved by using a dual-wavelength technique, with modified pseudoheterodyne signal recovery. Single-valued, multiple-fringe phase tracking is obtained by using a binary signal division technique. An average strain sensitivity of 0.050 +/- 0.02 deg microepsilon(-1) cm(-1) is found for sensors that are surface adhered to cantilever beams. The sensor system is applied successfully to the measurement of the local orientation of a 1-m structural beam, with an accuracy of +/-0.02 deg of beam slope. Limitations on the applicability of this sensing technique are discussed.

Distributed fiber optic sensing based on counterpropagating waves.

The spatially and temporally resolved birefringence of a single-mode optical fiber can be ascertained using backward stimulated Raman scattering. The magnitude of the birefringence is determined from the optical power exchanged between two counterpropagating light pulses. The degree to which a signal pulse is amplified by a pump pulse is governed by their relative states of polarization when they overlap. A novel normalization procedure is proposed that eliminates many of the unknowns. An example of how this technique could be used to evaluate a distributed strain field is provided.

Desipramine plasma levels and clinical response: evidence for a curvilinear relationship.

Twenty-six outpatients with major depression completed a 6-week, fixed dose trial of desipramine and provided plasma samples. Recovery after 6 weeks, defined in either of two ways, corresponded to lower desipramine levels, while clinical status at 4 weeks bore no apparent relationship to plasma levels. Upper limits of 140 or 155 ng/ml emerged depending on the outcome measure used. Patients with endogenous depression, those with primary depression, and those with abnormal dexamethasone suppression test results yielded similar therapeutic thresholds, while the sharpest blood level/response relationship emerged in the subgroup with an abnormal escape from dexamethasone.

Pharmacologic approaches to psychogenic polydipsia: case reports.

Psychiatric patients presenting with chronic psychogenic polydipsia are often difficult to treat with standard psychiatric interventions. Pharmacologic intervention was attempted in three patients and was successful in one. One patient had a significant and sustained reduction of water intake while on 160 mg of propranolol. One patient did not improve with either propranolol or captopril while a third patient showed no improvement of serum sodium with demeclocycline nor reduction of water intake with propranolol. The potential mechanisms by which these pharmacologic agents might alter thirst in patients with primary polydipsia are discussed.

Larval development and dispersal at deep-sea hydrothermal vents.

Deep-sea hydrothermal vent communities exhibit an array of reproductive strategies. Although a few vent species undergo planktotrophic, high-dispersal modes of development, most exhibit relatively low dispersal, but probably free-swimming nonplanktotrophic development. This predominance of nonplanktotrophy may be largely a reflection of phylogenetic constraints on the vent colonizing taxa; intervent dispersal among these forms may be facilitated by reduced developmental rates in the cold abyssal waters away from the vents. It is proposed that for those vent species with nonplanktotrophic development, larval dispersal is a stepwise process with oceanic ridge axes serving as discrete dispersal corridors.

A cellulolytic nitrogen-fixing bacterium cultured from the gland of deshayes in shipworms (bivalvia: teredinidae).

A novel bacterium has been isolated in pure culture from the gland of Deshayes in six species of teredinid bivalves. It is the first bacterium known to both digest cellulose and fix nitrogen, and it is a participant in a unique symbiotic relation with shipworms that may explain how teredinids are able to use wood as their principal food source.