Toward an integrated multi-gigahertz ionizing particle diagnostic.

Needs arising at both current and future accelerator facilities call for the development of radiation-hardened position-sensing diagnostics that can operate with multi-GHz repetition rates. Such instruments are likely to also have applications in the diagnosis of rapid plasma behavior. Building on the recent work of our Advanced Accelerator Diagnostics Collaboration, we are exploring the development of integrated multi-GHz ionizing particle detection systems based on chemical-vapor deposition diamond sensors, with the initial goal of producing a quadrant detector that can determine the intensity and centroid position of a particle beam at a repetition rate between 5 and 10 GHz. Results from our initial high-speed characterization work are presented, including those from a single-channel sensor with a GHz response. Approaches to achieving multi-GHz (5-10 GHz) rate capability, including the design of a dedicated Application Specific Integrated Circuit and the use of 3D RF-solver computer aided design software, are presented and discussed in more detail. 3D RF simulations suggest clean pulses of duration less than 250 ps (FWHM less than 125 ps) can be achieved with the approaches developed by this work.

Smoking exposure trajectories and pulmonary function in early adulthood in a Brazilian cohort.

OBJECTIVES: To investigate smoking trajectories and their association with pulmonary function (PF) and respiratory symptoms at age 22. METHODS: Data from a population-based cohort study of 3350 individuals and their spirometries were analysed. The outcomes were: forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), forced expiratory flow at the mid expiratory phase (FEF25-75 %), FEV1/FVC and FEF25-75/FVC ratio. Smoking data were collected at perinatal follow-up (gestational exposure) and 15, 18 and 22 years. Group-based trajectory model was applied. RESULTS: Four groups were identified: no exposure (NE), gestational (GE), gestational and adulthood (GAE) and continuous (CE) exposure. Both CE and GAE trajectories were associated with lower values of FEV1/FVC (-1.77pp; p = 0.01 and -1.58 pp; p<0.001 respectively) and FEF25-75/FVC ratio (-7.27pp; p = 0.019 and -6.04pp; p<0.001 respectively) compared to the NE trajectory. Lower FEV1 and FEF25-75 % values were also related to the GAE trajectory (-68 ml; p = 0.03 and -253 ml/s;p<0.001 respectively). Compared to those who never smoked, individuals who smoked 10 or more cigarettes daily presented a reduction in the FEV1/FVC ratio by 1.37pp (p<0.001), FEF25-75 % by 126 ml (p = 0.012) and FEF25-75 %/FVC ratio by 3.62pp (p = 0.011). CE trajectory showed higher odds of wheezing (OR 4.14; p<0.001) and cough (OR 2.39; p = 0.002) compared to the non-exposed group. CONCLUSIONS: The in-uterus exposure to maternal smoking reduces PF later in life. However, the perpetuation of smoking behaviour throughout adolescence and early adulthood is determinant for PF main reduction and the emergence of respiratory-related symptoms.

Use of diamond sensors for a high-flux, high-rate X-ray pass-through diagnostic.

X-ray free-electron lasers (XFELs) deliver pulses of coherent X-rays on the femtosecond time scale, with potentially high repetition rates. While XFELs provide high peak intensities, both the intensity and the centroid of the beam fluctuate strongly on a pulse-to-pulse basis, motivating high-rate beam diagnostics that operate over a large dynamic range. The fast drift velocity, low X-ray absorption and high radiation tolerance properties of chemical vapour deposition diamonds make these crystals a promising candidate material for developing a fast (multi-GHz) pass-through diagnostic for the next generation of XFELs. A new approach to the design of a diamond sensor signal path is presented, along with associated characterization studies performed in the XPP endstation of the LINAC Coherent Light Source (LCLS) at SLAC. Qualitative charge collection profiles (collected charge versus time) are presented and compared with those from a commercially available detector. Quantitative results on the charge collection efficiency and signal collection times are presented over a range of approximately four orders of magnitude in the generated electron-hole plasma density.

Household air pollution and COPD: cause and effect or confounding by other aspects of poverty?

SETTING: Household air pollution (HAP) and chronic obstructive pulmonary disease (COPD) are both major public health problems, reported to cause around 4 million and 3 million deaths every year, respectively. The great majority of these deaths, as well as the burden of disease during life is felt by people in low- and middle-income countries (LMICs).OBJECTIVE and DESIGN: The extent to which HAP causes COPD is controversial; we therefore undertook this review to offer a viewpoint on this from the Global Initiative for COPD (GOLD).RESULTS: We find that while COPD is well-defined in many studies on COPD and HAP, there are major limitations to the definition and measurement of HAP. It is thus difficult to disentangle HAP from other features of poverty that are themselves associated with COPD. We identify other limitations to primary research studies, including the use of cross-sectional designs that limit causal inference.CONCLUSION: There is substantial preventable morbidity and mortality associated with HAP, COPD and poverty, separately and together. Although it may not be possible to define clear causal links between HAP and COPD, there is a clear urgency to reduce the avoidable burden of disease these inflict on the world´s poor.

Functional impact of sequelae in drug-susceptible and multidrug-resistant tuberculosis.

BACKGROUND: Evidence on the impact of tuberculosis (TB) treatment on lung function is scarce. The aim of this study was to evaluate post-treatment sequelae in drug-susceptible and drug-resistant-TB (DR-TB) cases in Mexico and Italy.METHODS: At the end of TB treatment the patients underwent complete clinical assessment, functional evaluation of respiratory mechanics, gas exchange and a 6-minute walking test. Treatment regimens (and definitions) recommended by the World Health Organization were used throughout.RESULTS: Of 61 patients, 65.6% had functional impairment, with obstruction in 24/61 patients (39.4%), and 78% with no bronchodilator response. These effects were more prevalent among DR-TB cases (forced expiratory volume in 1 s/forced vital capacity [FEV1/FVC] < lower limit of normality, 14/24 vs. 10/34; P = 0.075). DR-TB patients showed moderately severe (FEV1 < 60%) and severe obstruction (FEV1 < 50%) (P = 0.008). Pre- and post-bronchodilator FEV1 and FEV1/FVC (% of predicted) were significantly lower among DR-TB cases. Plethysmography abnormalities (restriction, hyperinflation and/or air trapping) were more frequent among DR-TB cases (P = 0.001), along with abnormal carbon monoxide diffusing capacity (DLCO) (P = 0.003).CONCLUSION: The majority of TB patients suffer the consequences of post-treatment sequelae (of differing levels), which compromise quality of life, exercise tolerance and long-term prognosis. It is therefore important that lung function is comprehensively evaluated post-treatment to identify patient needs for future medication and pulmonary rehabilitation.

Relevance of 3D virtual planning in predicting bony interferences between distal and proximal fragments after sagittal split osteotomy.

After sagittal split osteotomy, the mandibular distal and proximal fragments do not always align themselves passively to one another, resulting in bony interferences and subsequent anomalous settlement of the condyles. Predicting these interferences could be an important ancillary procedure for avoiding intra- and postoperative surgical complications, rendering orthognathic surgery more effective and safer. This study evaluated the relevance of virtual surgical planning in assessing the displacement of the proximal segments after virtual distal segment repositioning, for predicting bony interferences between the segments and thus avoiding related intra- and postoperative surgical complications. The presence of interferences between the distal and proximal segments was compared between virtually predicted (computer-assisted simulation surgery, Dolphin software) and real cases in 100 consecutive patients diagnosed with dentofacial deformities who underwent orthognathic surgery with mandibular repositioning (using a short lingual osteotomy (SLO)). The results indicated that clockwise rotation of the mandible was the mandibular movement most prone to segment interference. Furthermore, virtual planning was sensitive (100%) but had low specificity (51.6%) in predicting proximal and distal segment interferences. This low specificity was due to the software-based automated design of the mandibular osteotomy, where the length of the distal segment was longer than the real SLO, and the mandibular ramus sagittal split was located just behind Spix's spine. Thus, more precise simulated osteotomies are needed to further validate the accuracy of virtual planning for this purpose.

Detection theory for accurate and non-invasive skin cancer diagnosis using dynamic thermal imaging.

Skin cancer is the most common cancer in the United States with over 3.5M annual cases. Presently, visual inspection by a dermatologist has good sensitivity (> 90%) but poor specificity (< 10%), especially for melanoma, which leads to a high number of unnecessary biopsies. Here we use dynamic thermal imaging (DTI) to demonstrate a rapid, accurate and non-invasive imaging system for detection of skin cancer. In DTI, the lesion is cooled down and the thermal recovery is recorded using infrared imaging. The thermal recovery curves of the suspected lesions are then utilized in the context of continuous-time detection theory in order to define an optimal statistical decision rule such that the sensitivity of the algorithm is guaranteed to be at a maximum for every prescribed false-alarm probability. The proposed methodology was tested in a pilot study including 140 human subjects demonstrating a sensitivity in excess of 99% for a prescribed specificity in excess of 99% for detection of skin cancer. To the best of our knowledge, this is the highest reported accuracy for any non-invasive skin cancer diagnosis method.

Comparison of bacteriological conversion and treatment outcomes among MDR-TB patients with and without diabetes in Mexico: Preliminary data.

Diabetes mellitus (DM) is a well-known risk factor for tuberculosis (TB). However, it is not known to what extent DM affects the outcome in patients with multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB) treated with second-line anti-TB drugs. The objective of this study was to compare the microbiological evolution (sputum smear and culture conversion) and final outcomes of MDR/XDR-TB patients with and without DM, managed at the national TB reference centre in Mexico City. RESULTS: Ninety patients were enrolled between 2010 and 2015: 73 with MDR-TB (81.1%), 11 with pre-XDR-TB (e.g. MDR-TB with additional resistance to one injectable drug or a fluoroquinolone, 12.2%) and 6 (6.7%) with XDR-TB. Out of these, 49 (54.4%) had DM and 42 (86%) were undergoing insulin treatment. No statistically significant differences were found in treatment outcomes comparing DM vs. non-DM MDR-TB cases: 18/32 (56.3%) of DM cases and 19/24 (79.2%) non DM patients achieved treatment success (p=0.07). The time to sputum smear and culture conversion was longer (although not statistically) in patients without DM, as follows: the mean (±SD) time to sputum smear conversion was 53.9 (±31.4) days in DM patients and 65.2 (±34.8) days in non-DM ones (p=0.15), while the time to culture conversion was 66.2 (±27.6) days for DM and 81.4 (±37.7) days for non-DM MDR-TB cases (p=0.06). CONCLUSIONS: The study results support the Mexican National TB programme to strengthen its collaboration with the DM programme, as an entry point for TB (and latent TB infection) screening and management.

Cationic porphyrin-mediated photodynamic inactivation of Candida biofilms and the effect of miconazole.

The formation of biofilms by Candida and the increasing resistance of Candida species to antifungals contribute to the high recurrence rates of denture stomatitis. This increase has stimulated an interest in antimicrobial photodynamic therapy (aPDT) as an alternative treatment. We examined the photoactivity of the porphyrin-based photosensitizer, TMP-1363, against biofilms of C. albicans, C. glabrata, C. tropicalis and C. parapsilosis, and the effect of the combined use of miconazole and aPDT. Biofilms of three American Type Culture Collection (ATCC) strains and four clinical isolates developed on poly(methyl methacrylate) (PMMA) disks, were incubated with miconazole, followed by treatment with TMP-1363 for 30 min at 37°C. The plates were exposed to broadband visible light at a distance of 10 cm to the plate, for 30 min (irradiance at the surface of the plate: 32.5 mW/cm2). The metabolic activity of the biofilms was measured by the XTT assay. ATCC strains and C. glabrata 7531/06 were not sensitive to TMP-aPDT, whereas the metabolic activities of the remaining three clinical isolates were reduced to 64.2 ± 5.5% of controls. Miconazole at 25 µg/ml decreased the viability of all strains except the ATTCC strain C. albicans MYA274; however its combination with aPDT was effective against this strain, suggesting a synergistic interaction. Effects of miconazole and aPDT on C. albicans MYA 2732, C. albicans 6122/06 were additive. With C. tropicalis and C. parapsilosis, the combined treatment had a higher, but not entirely additive, cytotoxic effect. The combined use of miconazole and TMP-aPDT is advantageous in the treatment of biofilms of a number of Candida species and strains, but not all. The molecular basis of this differential response is not known.

[Robotic-assisted laparoscopic myomectomy and pregnancy. Case report]. / Miomectomía laparoscópica asistida por robot y embarazo. Reporte de caso.

BACKGROUND: Reproductive surgery preserves, enhances or restores fertility. The minimal access surgery offers many benefits in relation to open surgery. Robot-assisted laparoscopic surgery is a relatively new technique in the field of gynecological surgery. CLINICAL CASE: A 30-year-old female patient, with primary infertility of five years of evolution in who uterine myomatosis of large elements was diagnosed and robot-assisted laparoscopic surgery was indicated. CONCLUSION: The advantages of robot-assisted laparoscopic surgery are: lower blood loss, hospital stay and postoperative pain and faster reinstatement to normal activities, in addition to a promising reproductive outcome for the patient.

The global burden of chronic respiratory disease in adults.

With an aging global population, chronic respiratory diseases are becoming a more prominent cause of death and disability. Age-standardised death rates from chronic obstructive pulmonary disease (COPD) are highest in low-income regions of the world, particularly South Asia and sub-Saharan Africa, although airflow obstruction is relatively uncommon in these areas. Airflow obstruction is, by contrast, more common in regions with a high prevalence of cigarette smoking. COPD mortality is much more closely related to the prevalence of a low forced vital capacity which is, in turn, associated with poverty. Mortality from asthma is less common than mortality from COPD, but it is also relatively more common in poorer areas, particularly Oceania, South and South-East Asia, the Middle East and Africa. Again this contrasts with the asthma prevalence among adults, which is highest in high-income regions. In high-income areas, mortality due to asthma, which is predominantly an adult problem, has fallen substantially in recent decades with the spread of new guidelines for treatment that emphasise the use of inhaled steroids to control the disease. Although mortality rates have been falling, the prevalence of atopy has been increasing between generations in Western Europe. Changes in the prevalence of wheeze among adults has been more varied and may have been influenced by the reduction in smoking and the increase in the use of inhaled steroids.

Summarising published results from spirometric surveys of COPD: the problem of inconsistent definitions.

SETTING: The use of different spirometric definitions for chronic obstructive pulmonary disease (COPD) has made an informative review of the available prevalence surveys impossible. OBJECTIVE: To derive adjustment factors that allow the comparison of studies using different spirometric criteria. METHODS: Pre- and post-bronchodilator one-second forced expiratory volume (FEV1) and forced vital capacity (FVC) values were taken from the Burden of Obstructive Lung Disease (BOLD) survey in 16 centres. Using a post-bronchodilator FEV1/FVC ratio less than the lower limit of normal (LLN) as our reference prevalence, we calculated simple multiplicative adjustments to transform other reported prevalence estimates to reference values. These adjustments were then tested on independent data sets from six further BOLD centres and five centres from the PLATINO study, a Latin American survey on obstructive lung disease. RESULTS: Prevalence estimates based on pre-bronchodilator fixed-ratio measurements were 5-25% higher than reference values, and were strongly positively biased with age and prevalence level. Applying simple adjustments provided prevalence estimates that were almost unbiased and within 5% of the reference values. CONCLUSIONS: Using the BOLD data, we have been able to estimate COPD prevalences based on post-bronchodilator FEV1/FVC < LLN by adjusting estimates based on other common definitions, enabling more meaningful comparisons of published findings.

Treatment-refractory actinic keratoses successfully treated using simultaneous combination topical 5-fluorouracil cream and imiquimod cream: a case-control study.

BACKGROUND: Most actinic keratoses (AKs) respond to standard treatments, but a subset persist and require further intervention. We report a series of 10 patients with AKs that failed to respond to conventional treatment with cryotherapy and topical monotherapy but responded completely to simultaneous therapy with topical 5-fluorouracil (5-FU) and imiquimod creams. OBJECTIVE: To report the success of this combination therapy in refractory AKs and to determine whether any clinical or histologic features predict for treatment resistance. METHODS: Case-control study with two control groups matched to each patient according to lesion location and sex. RESULTS: Mean lesion diameter (p < .001), lesion diameter greater than 1 cm (p < .001), and the presence of pain (p = .01) were statistically associated with failure of cryotherapy and topical monotherapy. None of the histologic features evaluated were found to be statistically significant, although thicker epidermis was nearly so (p = .054). CONCLUSIONS: In patients who have failed standard therapy for AKs, combination treatment using topical 5-FU and imiquimod cream may be an effective alternative therapeutic strategy. Larger lesion diameter, specifically greater than 1 cm, and the presence of pain predict conventional treatment resistance.