To update the accelerated partial breast irradiation Consensus Statement published in 2009 and provide guidance on use of intraoperative radiation therapy (IORT) for partial breast irradiation in ...early-stage breast cancer, based on published evidence complemented by expert opinion.
A systematic PubMed search using the same terms as the original Consensus Statement yielded 419 articles; 44 articles were selected. The authors synthesized the published evidence and, through a series of conference calls and e-mails, reached consensus regarding the recommendations.
The new recommendations include lowering the age in the "suitability group" from 60 to 50 years and in the "cautionary group" to 40 years for patients who meet all other elements of suitability (Table 1). Patients with low-risk ductal carcinoma in situ, as per Radiation Therapy Oncology Group 9804 criteria, were categorized in the "suitable" group. The task force agreed to maintain the current criteria based on margin status. Recommendations for the use of IORT for breast cancer patients include: counseling patients regarding the higher risk of ipsilateral breast tumor recurrence with IORT compared with whole breast irradiation; the need for prospective monitoring of long-term local control and toxicity with low-energy radiograph IORT given limited follow-up; and restriction of IORT to women with invasive cancer considered "suitable."
These recommendations will provide updated clinical guidance regarding use of accelerated partial breast irradiation for radiation oncologists and other specialists participating in the care of breast cancer patients.
Balancing multiple competing and conflicting objectives is an essential task for any artificial intelligence tasked with satisfying human values or preferences. Conflict arises both from misalignment ...between individuals with competing values, but also between conflicting value systems held by a single human. Starting with principle of loss-aversion, we designed a set of soft maximin function approaches to multi-objective decision-making. Bench-marking these functions in a set of previously-developed environments, we found that one new approach in particular, ‘split-function exp-log loss aversion’ (SFELLA), learns faster than the state of the art thresholded alignment objective method Vamplew (Engineering Applications of Artificial Intelligenceg 100:104186, 2021) on three of four tasks it was tested on, and achieved the same optimal performance after learning. SFELLA also showed relative robustness improvements against changes in objective scale, which may highlight an advantage dealing with distribution shifts in the environment dynamics. We further compared SFELLA to the multi-objective reward exponentials (MORE) approach, and found that SFELLA performs similarly to MORE in a simple previously-described foraging task, but in a modified foraging environment with a new resource that was not depleted as the agent worked, SFELLA collected more of the new resource with very little cost incurred in terms of the old resource. Overall, we found SFELLA useful for avoiding problems that sometimes occur with a thresholded approach, and more reward-responsive than MORE while retaining its conservative, loss-averse incentive structure.
The successful treatment of acute leukemias with allogeneic hematopoietic cell transplantation (allo-HCT) is limited by acute graft-versus-host disease (GVHD). Because microRNA-155 (miR-155) ...regulates activation of the innate immune system, we aimed to determine its function in dendritic cells (DCs) during GVHD in an experimental model. We observed that miR-155 deficiency of the recipient led to improved survival, reduced serum levels of proinflammatory cytokines, and lower GVHD histopathology scores. In addition, miR-155−/− bone marrow chimeric mice receiving allo-HCT and miR-155−/− DCs showed that miR-155 deficiency in the DC compartment was responsible for protection from GVHD. Activated miR-155−/− DCs displayed lower expression of various purinergic receptors and impaired migration toward adenosine triphosphate (ATP). Microarray analysis of lipopolysaccharide/ATP-stimulated miR-155−/− DCs revealed mitogen-activated protein kinase pathway dysregulation and reduced inflammasome-associated gene expression. Consistent with this gene expression data, we observed reduced ERK activation, caspase-1 cleavage, and IL-1β production in miR-155−/− DCs. The connection between miR-155 and inflammasome activation was supported by the fact that Nlrp3/miR-155 double-knockout allo-HCT recipient mice had no increased protection from GVHD compared with Nlrp3−/− recipients. This study indicates that during GVHD, miR-155 promotes DC migration toward sites of ATP release accompanied by inflammasome activation. Inhibiting proinflammatory miR-155 by antagomir treatment could help reduce this complication of allo-HCT.
•GVHD induction is dependent on functional miR-155 in DCs of the allo-HCT recipient.•MiR-155 deficiency reduces ATP-mediated cell migration, ERK and inflammasome activation, and IL-1β production of DCs.
The incidence of early-stage non-small cell lung cancer (NSCLC) among the elderly is expected to rise dramatically owing to demographic trends and increased computed tomographic screening. However, ...to our knowledge, no modern trials have compared the most common treatments for NSCLC.
To determine clinical characteristics and survival outcomes associated with the 3 most commonly used definitive therapies for early-stage NSCLC in the elderly.
The Surveillance, Epidemiology, and End Results database linked to Medicare was used to determine the baseline characteristics and outcomes of 9093 patients with early-stage, node-negative NSCLC who underwent definitive treatment consisting of lobectomy, sublobar resection, or stereotactic ablative radiotherapy (SABR) from January 1, 2003, through December 31, 2009.
Overall and lung cancer-specific survival were compared using Medicare claims through December 31, 2012. We used proportional hazards regression and propensity score matching to adjust outcomes for key patient, tumor, and practice environment factors.
The median age was 75 years, and treatment distribution was 79.3% for lobectomy, 16.5% for sublobar resection, and 4.2% for SABR. Unadjusted 90-day mortality was highest for lobectomy (4.0%) followed by sublobar resection (3.7%; P = .79) and SABR (1.3%; P = .008). At 3 years, unadjusted mortality was lowest for lobectomy (25.0%), followed by sublobar resection (35.3%; P < .001) and SABR (45.1%; P < .001). Proportional hazards regression demonstrated that sublobar resection was associated with worse overall survival (adjusted hazard ratio AHR, 1.32 95% CI, 1.20-1.44; P < .001) and lung cancer-specific survival (AHR, 1.50 95% CI, 1.29-1.75; P < .001) compared with lobectomy. Propensity score-matching analysis reiterated these findings for overall survival (AHR, 1.36 95% CI, 1.17-1.58; P < .001) and lung cancer-specific survival (AHR, 1.46 95% CI, 1.13-1.90; P = .004). In proportional hazards regression, SABR was associated with better overall survival than lobectomy in the first 6 months after diagnosis (AHR, 0.45 95% CI, 0.27-0.75; P < .001) but worse survival thereafter (AHR, 1.66 95% CI, 1.39-1.99; P < .001). Propensity score-matching analysis of well-matched SABR and lobectomy cohorts demonstrated similar overall survival in both groups (AHR, 1.01 95% CI, 0.74-1.38; P = .94).
Lobectomy was associated with better outcomes than sublobar resection in elderly patients with early-stage NSCLC. Propensity score matching suggests that SABR may be a good option among patients with very advanced age and multiple comorbidities.
Movement of the visual environment presented through virtual reality (VR) has been shown to invoke postural adjustments measured by increased body sway. The effect of auditory information on body ...sway seems to be dependent on context with sounds such as white noise, tones, and music being used to amplify or suppress sway. This study aims to show that music manipulated to match VR motion further increases body sway. Twenty-eight subjects stood on a force plate and experienced combinations of 3 visual conditions (VR translation in the AP direction at 0.1 Hz, no translation, and eyes closed) and 4 music conditions (Mozart’s Jupiter Symphony modified to scale volume at 0.1 Hz and 0.25 Hz, unmodified music, and no music) Body sway was assessed by measuring center of pressure (COP) velocities and RMS. Cross-coherence between the body sway and the 0.1 Hz and 0.25 Hz stimuli was also determined. VR translations at 0.1 Hz matched with 0.1Hz shifts in music volume did not lead to more body sway than observed in the no music and unmodified music conditions. Researchers and clinicians may consider manipulating sound to enhance VR induced body sway, but findings from this study would not suggest using volume to do so.
Commonly consumed foods and beverages can contain chemicals with reported carcinogenic activity in rodent models. Moreover, exposures to some of these substances have been associated with increased ...cancer risks in humans. Food-borne carcinogens span a range of chemical classes and can arise from natural or anthropogenic sources, as well as form endogenously. Important considerations include the mechanism(s) of action (MoA), their relevance to human biology, and the level of exposure in diet. The MoAs of carcinogens have been classified as either DNA-reactive (genotoxic), involving covalent reaction with nuclear DNA, or epigenetic, involving molecular and cellular effects other than DNA reactivity. Carcinogens are generally present in food at low levels, resulting in low daily intakes, although there are some exceptions. Carcinogens of the DNA-reactive type produce effects at lower dosages than epigenetic carcinogens. Several food-related DNA-reactive carcinogens, including aflatoxins, aristolochic acid, benzene, benzoapyrene and ethylene oxide, are recognized by the International Agency for Research on Cancer (IARC) as causes of human cancer. Of the epigenetic type, the only carcinogen considered to be associated with increased cancer in humans, although not from low-level food exposure, is dioxin (TCDD). Thus, DNA-reactive carcinogens in food represent a much greater risk than epigenetic carcinogens.
New Nutri-Grade labelling, aimed at reducing Singaporeans' sugar consumption will be implemented for all pre-packaged non-alcoholic beverages (NABs) sold in retail outlets from end 2021 onwards. It ...is expected such labelling will have a major impact on sugar content of beverages, as well as the replacement of sugar with non-caloric alternatives.
This study used product label data obtained from in-store surveys to investigate sugar and sweetener composition of NABs present on the Singapore market. Using this data we calculated products prospective Nutri-Grade classification in order to compare the current market composition with relation to sugar and/or sweetener use.
Over half of the NABs on market were sweetened with sugar (59%) and were associated with less healthy Nutri-Grades of 'C' and 'D'. The use of natural sweeteners; Stevia and Monk fruit, remains low (6%).
With continuous efforts by the government in promoting public health nutrition, it is expected that there will be a greater usage of sugar substitutes among NABs in response to the upcoming implementation of Nutri-Grade and ever-fluctuating consumers' demands. The data collected in this study provide a point estimate (July-September 2020) on market composition and use of both sugar and artificial sweeteners in beverages prior to integration of the mandatory labelling requirements.
Chronic musculoskeletal disorders are a prevalent and costly global health issue. A new form of exercise therapy focused on loading and resistance programmes that temporarily aggravates a patient's ...pain has been proposed. The object of this review was to compare the effect of exercises where pain is allowed/encouraged compared with non-painful exercises on pain, function or disability in patients with chronic musculoskeletal pain within randomised controlled trials.
Two authors independently selected studies and appraised risk of bias. Methodological quality was evaluated using the Cochrane risk of bias tool, and the Grading of Recommendations Assessment system was used to evaluate the quality of evidence.
The literature search identified 9081 potentially eligible studies. Nine papers (from seven trials) with 385 participants met the inclusion criteria. There was short- term significant difference in pain, with moderate quality evidence for a small effect size of -0.27 (-0.54 to -0.05) in favour of painful exercises. For pain in the medium and long term, and function and disability in the short, medium and long term, there was no significant difference.
Protocols using painful exercises offer a small but significant benefit over pain-free exercises in the short term, with moderate quality of evidence. In the medium and long term there is no clear superiority of one treatment over another. Pain during therapeutic exercise for chronic musculoskeletal pain need not be a barrier to successful outcomes. Further research is warranted to fully evaluate the effectiveness of loading and resistance programmes into pain for chronic musculoskeletal disorders.
CRD42016038882.
The rapidly expanding field of microbiome studies offers investigators a large choice of methods for each step in the process of determining the microorganisms in a sample. The human cervicovaginal ...microbiome affects female reproductive health, susceptibility to and natural history of many sexually transmitted infections, including human papillomavirus (HPV). At present, long-term behavior of the cervical microbiome in early sexual life is poorly understood.
The V6 and V6-V9 regions of the 16S ribosomal RNA gene were amplified from DNA isolated from exfoliated cervical cells. Specimens from 10 women participating in the Natural History Study of HPV in Guanacaste, Costa Rica were sampled successively over a period of 5-7 years. We sequenced amplicons using 3 different platforms (Sanger, Roche 454, and Illumina HiSeq 2000) and analyzed sequences using pipelines based on 3 different classification algorithms (usearch, RDP Classifier, and pplacer).
Usearch and pplacer provided consistent microbiome classifications for all sequencing methods, whereas RDP Classifier deviated significantly when characterizing Illumina reads. Comparing across sequencing platforms indicated 7%-41% of the reads were reclassified, while comparing across software pipelines reclassified up to 32% of the reads. Variability in classification was shown not to be due to a difference in read lengths. Six cervical microbiome community types were observed and are characterized by a predominance of either G. vaginalis or Lactobacillus spp. Over the 5-7 year period, subjects displayed fluctuation between community types. A PERMANOVA analysis on pairwise Kantorovich-Rubinstein distances between the microbiota of all samples yielded an F-test ratio of 2.86 (p<0.01), indicating a significant difference comparing within and between subjects' microbiota.
Amplification and sequencing methods affected the characterization of the microbiome more than classification algorithms. Pplacer and usearch performed consistently with all sequencing methods. The analyses identified 6 community types consistent with those previously reported. The long-term behavior of the cervical microbiome indicated that fluctuations were subject dependent.
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