Many technological and methodical advances have made stereotactic body radiotherapy (SBRT) more accurate and more efficient during the last years. This study aims to investigate whether experience in ...SBRT and technological innovations also translated into improved local control (LC) and overall survival (OS).
A database of 700 patients treated with SBRT for lung metastases in 20 German centers between 1997 and 2014 was used for analysis. It was the aim of this study to investigate the impact of fluorodeoxyglucose positron-emission tomography (FDG-PET) staging, biopsy confirmation, image guidance, immobilization, and dose calculation algorithm, as well as the influence of SBRT experience, on LC and OS.
Median follow-up time was 14.3 months (range, 0-131.9 months), with 2-year LC and OS of 81.2% (95% confidence interval CI 75.8%-85.7%) and 54.4% (95% CI 50.2%-59.0%), respectively. In multivariate analysis, all treatment technologies except FDG-PET staging did not significantly influence outcome. Patients who received pre-SBRT FDG-PET staging showed superior 1- and 2-year OS of 82.7% (95% CI 77.4%-88.6%) and 64.8% (95% CI 57.5%-73.3%), compared with patients without FDG-PET staging resulting in 1- and 2-year OS rates of 72.8% (95% CI 67.4%-78.8%) and 52.6% (95% CI 46.0%-60.4%), respectively (P=.012). Experience with SBRT was identified as the main prognostic factor for LC: institutions with higher SBRT experience (patients treated with SBRT within the last 2 years of the inclusion period) showed superior LC compared with less-experienced centers (P≤.001). Experience with SBRT within the last 2 years was independent from known prognostic factors for LC.
Investigated technological and methodical advancements other than FDG-PET staging before SBRT did not significantly improve outcome in SBRT for pulmonary metastases. In contrast, LC was superior with increasing SBRT experience of the individual center.
Summary Background Preclinical data suggest that general anaesthetics affect brain development. There is mixed evidence from cohort studies that young children exposed to anaesthesia can have an ...increased risk of poor neurodevelopmental outcome. We aimed to establish whether general anaesthesia in infancy has any effect on neurodevelopmental outcome. Here we report the secondary outcome of neurodevelopmental outcome at 2 years of age in the General Anaesthesia compared to Spinal anaesthesia (GAS) trial. Methods In this international assessor-masked randomised controlled equivalence trial, we recruited infants younger than 60 weeks postmenstrual age, born at greater than 26 weeks' gestation, and who had inguinal herniorrhaphy, from 28 hospitals in Australia, Italy, the USA, the UK, Canada, the Netherlands, and New Zealand. Infants were randomly assigned (1:1) to receive either awake-regional anaesthesia or sevoflurane-based general anaesthesia. Web-based randomisation was done in blocks of two or four and stratified by site and gestational age at birth. Infants were excluded if they had existing risk factors for neurological injury. The primary outcome of the trial will be the Wechsler Preschool and Primary Scale of Intelligence Third Edition (WPPSI-III) Full Scale Intelligence Quotient score at age 5 years. The secondary outcome, reported here, is the composite cognitive score of the Bayley Scales of Infant and Toddler Development III, assessed at 2 years. The analysis was as per protocol adjusted for gestational age at birth. A difference in means of five points (1/3 SD) was predefined as the clinical equivalence margin. This trial is registered with ANZCTR, number ACTRN12606000441516 and ClinicalTrials.gov , number NCT00756600. Findings Between Feb 9, 2007, and Jan 31, 2013, 363 infants were randomly assigned to receive awake-regional anaesthesia and 359 to general anaesthesia. Outcome data were available for 238 children in the awake-regional group and 294 in the general anaesthesia group. In the as-per-protocol analysis, the cognitive composite score (mean SD) was 98·6 (14·2) in the awake-regional group and 98·2 (14·7) in the general anaesthesia group. There was equivalence in mean between groups (awake-regional minus general anaesthesia 0·169, 95% CI −2·30 to 2·64). The median duration of anaesthesia in the general anaesthesia group was 54 min. Interpretation For this secondary outcome, we found no evidence that just less than 1 h of sevoflurane anaesthesia in infancy increases the risk of adverse neurodevelopmental outcome at 2 years of age compared with awake-regional anaesthesia. Funding Australia National Health and Medical Research Council (NHMRC), Health Technologies Assessment-National Institute for Health Research UK, National Institutes of Health, Food and Drug Administration, Australian and New Zealand College of Anaesthetists, Murdoch Childrens Research Institute, Canadian Institute of Health Research, Canadian Anesthesiologists' Society, Pfizer Canada, Italian Ministry of Heath, Fonds NutsOhra, and UK Clinical Research Network (UKCRN).
The development of a permissive small animal model for the study of human immunodeficiency virus type (HIV)-1 pathogenesis and the testing of antiviral strategies has been hampered by the inability ...of HIV-1 to infect primary rodent cells productively. In this study, we explored transgenic rats expressing the HIV-1 receptor complex as a susceptible host. Rats transgenic for human CD4 (hCD4) and the human chemokine receptor CCR5 (hCCR5) were generated that express the transgenes in CD4(+) T lymphocytes, macrophages, and microglia. In ex vivo cultures, CD4(+) T lymphocytes, macrophages, and microglia from hCD4/hCCR5 transgenic rats were highly susceptible to infection by HIV-1 R5 viruses leading to expression of abundant levels of early HIV-1 gene products comparable to those found in human reference cultures. Primary rat macrophages and microglia, but not lymphocytes, from double-transgenic rats could be productively infected by various recombinant and primary R5 strains of HIV-1. Moreover, after systemic challenge with HIV-1, lymphatic organs from hCD4/hCCR5 transgenic rats contained episomal 2-long terminal repeat (LTR) circles, integrated provirus, and early viral gene products, demonstrating susceptibility to HIV-1 in vivo. Transgenic rats also displayed a low-level plasma viremia early in infection. Thus, transgenic rats expressing the appropriate human receptor complex are promising candidates for a small animal model of HIV-1 infection.
Syphilis: A Reemerging Infection Mattei, Peter L., MD; Beachkofsky, Thomas M., MD; Gilson, Robert T., MD ...
American family physician,
09/2012, Letnik:
86, Številka:
5
Journal Article
Recenzirano
Rates of primary and secondary syphilis have increased in the past decade, warranting renewed attention to the diagnosis and treatment of this disease. Men who have sex with men are particularly ...affected; however, increases in infection rates have also been noted in women, as well as in all age groups and ethnicities. Physicians need to vigilantly screen high-risk patients. The concurrent rise in congenital syphilis also requires special attention and reemphasizes the need for continued early prenatal care and syphilis screening for all pregnant women. Syphilis infection in patients coinfected with human immunodeficiency virus has also become more common. New experimental diagnostic approaches, including using the B cell chemoattractant chemokine (CXC motif) ligand 13 as a cerebrospinal fluid marker, may help identify suspected neurosyphilis cases. Additionally, point-of-care immunochromatographic strip testing has been suggested for screening high-risk populations in developing countries. Nontreponemal screening tests followed by treponemal confirmatory tests continue to be standard diagnostics; hwever, interpreting false-negative and false-positive test results, and identifying serofast reactions, can be challenging. Although doxycycline, tetracycline, ceftriaxone, and azithromycin have been used to successfully treat syphilis, penicillin remains the drug of choice in all stages of infection and is the therapy recommended by the Centers for Disease Control and Prevention. Close follow-up is necessary to ensure treatment success.
For countries that have not adopted this practice, including Australia, models provide necessary estimates in lieu of official information. Since the publication of our paper1 there have been further ...improvements, including the recent data of AIS longline fishing effort for 2018 with updated gear assignments based on convolutional neural networks and data for more vessels. ...an important question raised2 is whether the reclassification of the gear types of 47 vessels directly affects the calculations of fishing exposure and our conclusions. Within the Oceania region used in our paper, Western Australia comprises 2.2% and GBR 0.35%. ...the areas comprising reclassifications provide a minor contribution to the spatial overlap and FEI values that we calculated not only globally but also within the Oceania region. Illegal, unreported and unregulated fishers are known to target sharks-including tiger sharks9-for fins, an ongoing threat that has been a major problem in Australia's NWS7, which overlaps with the tiger shark hotspot8. ...it cannot be discounted that the shark hotspot overlaps with non-AIS monitored fishing activity, especially as more than 0.5 million km2 of the NWS remains open to commercial shark fishing10.
...we account for selectivity by focusing our fisheries-independent spatial estimates directly on individuals that were actually caught by the focal fisheries. ...the commercially valuable sharks ...that we tracked are seldom discarded by major high-seas longlining fleets8, indicating that an implicit assumption of a fishing mortality probability of one does not substantially overestimate the mortality that occurs. Regarding FEI being related to fishing-induced shark mortality, we stated1 that the significant positive relationship between Food and Agriculture Organization (FAO) fishery landings data and individual-species mean FEI "implies that the index reflects fishing-induced shark mortality". ...we disagree that our analyses do not support our conclusion of limited spatial refuge for pelagic sharks from current levels of fishing effort in Areas Beyond National Jurisdictions (ABNJs).
Defect management in perovskite solar cells (PSCs) via surface passivation has become a cornerstone in maximizing both stability and solar‐to‐electrical power conversion efficiency (PCE) of devices ...by reducing defect densities and/or improving energetic alignment between the perovskite and charge‐transporting layers. Despite this, few reports explore the use of roll‐to‐roll compatible technologies to deposit such interfacial treatments, limiting the applicability of passivation in real‐world contexts. In this work, iso‐butylammonium bromide (i‐BABr) is spray‐coated onto a Cs0.15FA0.85PbI2.85Cl0.15 perovskite surface which is deposited using gas‐assisted ultrasonic spray coating. It is found that i‐BABr treatments result in the formation of a quasi‐2D perovskite layer. The spray‐coated surface treatment results in an impressive 80 mV improvement in the median open‐circuit voltage with respect to untreated devices. Importantly, the spray‐coated passivation results in very similar positive benefits to the application of spin‐coated treatments demonstrating the promise of the spray‐passivation methodology. It is shown that devices created in this manner demonstrate PCEs of up to 21.0% (19.4% stabilized), representing the highest reported efficiency for one‐step, spray‐coated methylammonium‐free PSCs. This work represents the first demonstration of a spray‐coated surface passivation treatment that is compatible with high‐throughput, roll‐to‐roll processing.
Interfacial treatments between perovskite active layers and charge‐transporting layers are a ubiquitous approach to reduce energetic losses in spin‐coated perovskite solar cells. Despite this, there have only been a handful of demonstrations of surface passivation via roll‐to‐roll compatible deposition technologies. It is demonstrated that the ultrasonic spray deposition of iso‐butylammonium bromide dimensionally engineers and passivates the perovskite: hole‐transporting layer interface.
Despite the incredible progress made, the highest efficiency perovskite solar cells are still restricted to small areas (<1 cm2). In large part, this stems from a poor understanding of the widespread ...spatial heterogeneity in devices. Conventional techniques to assess heterogeneities can be time consuming, operate only at microscopic length scales, and demand specialized equipment. We overcome these limitations by using luminescence imaging to reveal large, millimeter-scale heterogeneities in the inferred electronic properties. We determine spatially resolved maps of “charge collection quality”, measured using the ratio of photoluminescence intensity at open and short circuit. We apply these methods to quantify the inhomogeneities introduced by a wide range of transport layers, thereby ranking them by suitability for upscaling. We reveal that top-contacting transport layers are the dominant source of heterogeneity in the multilayer material stack. We suggest that this methodology can be used to accelerate the development of highly efficient, large-area modules, especially through high-throughput experimentation.
Summary Background Axitinib (AG-013736) is an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3. We aimed to assess the activity and safety of axitinib ...in patients with metastatic renal-cell cancer who had failed on previous cytokine-based treatment. Methods Between Oct 3, 2003, and April 7, 2004, 52 patients were enrolled. All patients who had at least one measurable target lesion received axitinib orally (starting dose 5 mg twice daily). The primary endpoint was objective response (ie, percentage of patients with confirmed complete response or partial response by use of Response Evaluation Criteria In Solid Tumors RECIST criteria. Secondary endpoints were duration of response, time to progression, overall survival, safety, pharmacokinetics, and patient-reported health-related quality of life. This trial is registered on the clinical trials site of the US National Cancer Institute website http://www.clinicaltrials.gov/ct/show/NCT00076011. Findings In an intention-to-treat analysis, two complete and 21 partial responses were noted, for an objective response rate of 44·2% (95% CI 30·5–58·7). Median response duration was 23·0 months (20·9–not estimable; range 4·2–29·8). However, 12 of 23 initial responders progressed with response duration ranging from 4·2 months to 26·5 months. Additionally, 22 patients showed stable disease for longer than 8 weeks, including 13 patients with stable disease for 24 weeks or longer. Four patients had early disease progression. Three patients had missing response data. Median time to progression was 15·7 months (8·4–23·4, range 0·03–31·5) and median overall survival was 29·9 months (20·3–not estimable; range 2·4–35·8). Treatment-related adverse events included diarrhoea, hypertension, fatigue, nausea, and hoarseness. Treatment-related hypertension occurred in 30 patients and resolved with antihypertensive treatment in all but eight patients, of whom seven patients had a history of hypertension at baseline. Interpretation Axitinib shows clinical activity in patients with cytokine-refractory metastatic renal-cell cancer. Although 28 patients had grade 3 or grade 4 treatment-related adverse events, these adverse events were generally manageable and controlled by dose modification or supportive care, or both. Further studies are needed to confirm these findings.
PDF
