Physical inactivity is an important contributor to non-communicable diseases in countries of high income, and increasingly so in those of low and middle income. Understanding why people are ...physically active or inactive contributes to evidence-based planning of public health interventions, because effective programmes will target factors known to cause inactivity. Research into correlates (factors associated with activity) or determinants (those with a causal relationship) has burgeoned in the past two decades, but has mostly focused on individual-level factors in high-income countries. It has shown that age, sex, health status, self-efficacy, and motivation are associated with physical activity. Ecological models take a broad view of health behaviour causation, with the social and physical environment included as contributors to physical inactivity, particularly those outside the health sector, such as urban planning, transportation systems, and parks and trails. New areas of determinants research have identified genetic factors contributing to the propensity to be physically active, and evolutionary factors and obesity that might predispose to inactivity, and have explored the longitudinal tracking of physical activity throughout life. An understanding of correlates and determinants, especially in countries of low and middle income, could reduce the effect of future epidemics of inactivity and contribute to effective global prevention of non-communicable diseases.
Abstract
Recent high-resolution simulations of early structure formation have shown that externally enriched halos may form some of the first metal-enriched stars. This study utilizes a 1 comoving ...Mpc
3
high-resolution simulation to study the enrichment process of metal-enriched halos down to
z
= 9.3. Our simulation uniquely tracks the metals ejected from Population III stars, and we use this information to identify the origin of metals within metal-enriched halos. These halos show a wide range of metallicities, but we find that the source of metals for ≳50% of metal-enriched halos is supernova explosions of Population III stars occurring outside their virial radii. The results presented here indicate that external enrichment by metal-free stars dominates the enrichment process of halos with virial mass below 10
6
M
⊙
down to
z
= 9.3. Despite the prevalence of external enrichment in low-mass halos, Population II stars forming due to external enrichment are rare because of the small contribution of low-mass halos to the global star formation rate combined with low metallicities toward the center of these halos resulting from metal ejecta from external sources mixing from the outside in. The enriched stars that do form through this process have absolute metallicities below 10
−3
Z
⊙
. We also find that the fraction of externally enriched halos increases with time: ∼90% of halos that are externally enriched have
M
vir
< 10
6
M
⊙
, and that pair-instability supernovae contribute the most to the enrichment of the intergalactic medium as a whole and are thus are the predominant supernova type contributing to the external enrichment of halos.
Breast conserving surgery (BCS) is an effective treatment for early-stage cancers as long as the margins of the resected tissue are free of disease according to consensus guidelines for patient ...management. However, 15% to 35% of patients undergo a second surgery since malignant cells are found close to or at the margins of the original resection specimen. This review highlights imaging approaches being investigated to reduce the rate of positive margins, and they are reviewed with the assumption that a new system would need high sensitivity near 95% and specificity near 85%. The problem appears to be twofold. The first is for complete, fast surface scanning for cellular, structural, and/or molecular features of cancer, in a lumpectomy volume, which is variable in size, but can be large, irregular, and amorphous. A second is for full, volumetric imaging of the specimen at high spatial resolution, to better guide internal radiologic decision-making about the spiculations and duct tracks, which may inform that surfaces are involved. These two demands are not easily solved by a single tool. Optical methods that scan large surfaces quickly are needed with cellular/molecular sensitivity to solve the first problem, but volumetric imaging with high spatial resolution for soft tissues is largely outside of the optical realm and requires x-ray, micro-CT, or magnetic resonance imaging if they can be achieved efficiently. In summary, it appears that a combination of systems into hybrid platforms may be the optimal solution for these two very different problems. This concept must be cost-effective, image specimens within minutes and be coupled to decision-making tools that help a surgeon without adding to the procedure. The potential for optical systems to be involved in this problem is emerging and clinical trials are underway in several of these technologies to see if they could reduce positive margin rates in BCS.
Solid organ transplant recipients are at an increased risk of developing skin cancers due to chronic immunosuppression, particularly with calcineurin inhibitors. Tacrolimus is the most prescribed ...calcineurin inhibitor in this patient cohort, and understanding tacrolimus concentrations in the skin will facilitate the development of anti-cancer preventive and therapeutic strategies. Here, we show that in mice, tacrolimus blood levels peaked rapidly ∼1 h post last oral dose while skin levels rose more slowly and remained high for at least 6 h. Subsequently, tacrolimus skin and blood concentrations were assessed in 15 kidney transplant recipients. The mean age was 61 years, the average time post-transplant was 7 years (range 0-21 years) and 87% were male. The average skin sampling time post tacrolimus dosing was 6 h 32 min. Skin tacrolimus concentrations ranged from 7.1 ng/g to 71.2 ng/g and correlated with blood concentrations (r = 0.6). Mouse and human mean skin concentrations were in a similar range. Our data suggests that tacrolimus measurements in the blood may be used to approximate tacrolimus concentrations in the skin of kidney transplant recipients, and further exploited for the delivery of anti-cancer therapies designed to antagonize the immunosuppressive effects of tacrolimus in the skin.
High positive margin rates in oncologic breast-conserving surgery are a pressing clinical problem. Volumetric X-ray scanning is emerging as a powerful ex vivo specimen imaging technique for analyzing ...resection margins, but X-rays lack contrast between non-malignant and malignant fibrous tissues. In this study, combined micro-CT and wide-field optical image radiomics were developed to classify malignancy of breast cancer tissues, demonstrating that X-ray/optical radiomics improve malignancy classification. Ninety-two standardized features were extracted from co-registered micro-CT and optical spatial frequency domain imaging samples extracted from 54 breast tumors exhibiting seven tissue subtypes confirmed by microscopic histological analysis. Multimodal feature sets improved classification performance versus micro-CT alone when adipose samples were included (AUC = 0.88 vs. 0.90; p-value = 3.65e-11) and excluded, focusing the classification task on exclusively non-malignant fibrous versus malignant tissues (AUC = 0.78 vs. 0.85; p-value = 9.33e-14). Extending the radiomics approach to high-dimensional optical data-termed "optomics" in this study-offers a promising optical image analysis technique for cancer detection. Radiomic feature data and classification source code are publicly available.
To prospectively assess quantitatively the inherent contrast of electromagnetic (EM) properties that can be imaged by using available technology in women with abnormal findings at conventional breast ...imaging who underwent subsequent biopsy.
The protocol was HIPAA compliant and approved by the institutional review board. All participants provided informed consent. Fifty-three women with normal (Breast Imaging Reporting and Data System BI-RADS category 1) and ninety-seven women with abnormal (BI-RADS category 4 or 5) screening mammograms were imaged with three EM imaging methods: electrical impedance spectroscopy (EIS), microwave imaging spectroscopy (MIS), and near-infrared spectral tomography (NIR). A region-of-interest (ROI) analysis was used to assess the EM image properties for comparison of findings with conventional image findings and correlation with specific pathologic parameters for women with abnormal findings. Statistical analyses were conducted.
One hundred fifty participants (age range, 35-81 years) were included. EM image property contrast ratios of 150%-200% were found in breast abnormality ROIs relative to the ipsilateral breast background. Analysis of variance demonstrated significant differences in ROI image summaries of mammographically normal versus abnormal breasts for EIS, across diagnostic groups for NIR, and for MIS (analysis restricted to lesions larger than 1 cm(3)). Receiver operating curve (ROC) analysis of the EM properties for cancers among subjects with BI-RADS category 4 or 5, compared with the EM properties for the subjects with normal breasts (BI-RADS category 1), yielded areas under the ROC curve ranging from 0.67 to 0.81. Pathologic correlations with mean vessel density, mean vessel area, and epithelium-to-stroma ratio suggest a biological origin of the EM image properties associated with disease.
Results from EM breast examinations provide statistical evidence of a mean increase in image contrast of 150%-200% between abnormal (benign and malignant) and normal breast tissue.
Objective: Suicide is the 10th leading cause of death in the United States. There are several important decisions that could confer later risk to a suicide attempt (e.g., how to store lethal means). ...Therefore, understanding how people make decisions that are relevant for suicide risk is an important area of study for suicidology. Human behavior diverges from perfectly rational economic decision making according to observable patterns based on predictable cognitive processes. Nudges attempt to diminish, leverage, or circumvent these deviations to increase the probability of a desired choice being selected or behavior being performed. One deviation from rationality is that human choice is context dependent. This deviation can be observed by introducing an objectively inferior alternative option (a decoy) into a choice array that alters an individual's preference. Using decoys could be one way to nudge people toward best practices in suicide prevention work. Method: This study examined if decoys could reliably alter participant preferences for suicide prevention resources using a hypothetical scenario in three separate online samples (i.e., general population, participants with recent suicidal thoughts, gun owners). Results: Our results found that introducing a slightly (but objectively) worse version of an existing suicide prevention resource increased the preference toward the slightly better option. Conclusions: These findings indicate that using decoys could be an effective nudge for influencing people's preference toward best practices. Most important, these findings highlight the importance of context effects on choice preference in suicide research and prevention efforts, as well as suggest irrational decision-making processes in suicide-relevant decision making.
What is the public health significance of this article?
Suicide-relevant decisions, such as choosing suicide prevention crisis resources, are context dependent and vulnerable to cognitive heuristics and biased decision making. Results from three studies suggested that using a time- and cost-effective behavioral economic intervention (i.e., nudges) can effectively alter preferences for suicide prevention resources. These studies indicate the importance of considering behavioral economic theory when understanding both distal (and likely proximal) suicide-relevant decision making.
Wilms tumor is a pediatric kidney cancer associated with inactivation of the WT1 tumor-suppressor gene in 5 to 10% of cases. Using a high-resolution screen for DNA copy-number alterations in Wilms ...tumor, we identified somatic deletions targeting a previously uncharacterized gene on the X chromosome. This gene, which we call WTX, is inactivated in approximately one-third of Wilms tumors (15 of 51 tumors). Tumors with mutations in WTX lack WT1 mutations, and both genes share a restricted temporal and spatial expression pattern in normal renal precursors. In contrast to biallelic inactivation of autosomal tumor-suppressor genes, WTX is inactivated by a monoallelic "single-hit" event targeting the single X chromosome in tumors from males and the active X chromosome in tumors from females.
Hyperspectral dark-field microscopy (HSDFM) and data cube analysis algorithms demonstrate successful detection and classification of various tissue types, including carcinoma regions in human ...post-lumpectomy breast tissues excised during breast-conserving surgeries.
We expand the application of HSDFM to the classification of tissue types and tumor subtypes in pre-histopathology human breast lumpectomy samples.
Breast tissues excised during breast-conserving surgeries were imaged by the HSDFM and analyzed. The performance of the HSDFM is evaluated by comparing the backscattering intensity spectra of polystyrene microbead solutions with the Monte Carlo simulation of the experimental data. For classification algorithms, two analysis approaches, a supervised technique based on the spectral angle mapper (SAM) algorithm and an unsupervised technique based on the
-means algorithm are applied to classify various tissue types including carcinoma subtypes. In the supervised technique, the SAM algorithm with manually extracted endmembers guided by H&E annotations is used as reference spectra, allowing for segmentation maps with classified tissue types including carcinoma subtypes.
The manually extracted endmembers of known tissue types and their corresponding threshold spectral correlation angles for classification make a good reference library that validates endmembers computed by the unsupervised
-means algorithm. The unsupervised
-means algorithm, with no
information, produces abundance maps with dominant endmembers of various tissue types, including carcinoma subtypes of invasive ductal carcinoma and invasive mucinous carcinoma. The two carcinomas' unique endmembers produced by the two methods agree with each other within
residual error margin.
Our report demonstrates a robust procedure for the validation of an unsupervised algorithm with the essential set of parameters based on the ground truth, histopathological information. We have demonstrated that a trained library of the histopathology-guided endmembers and associated threshold spectral correlation angles computed against well-defined reference data cubes serve such parameters. Two classification algorithms, supervised and unsupervised algorithms, are employed to identify regions with carcinoma subtypes of invasive ductal carcinoma and invasive mucinous carcinoma present in the tissues. The two carcinomas' unique endmembers used by the two methods agree to
residual error margin. This library of high quality and collected under an environment with no ambient background may be instrumental to develop or validate more advanced unsupervised data cube analysis algorithms, such as effective neural networks for efficient subtype classification.
As receptor-targeted therapeutics become increasingly used in clinical oncology, the ability to quantify protein expression and pharmacokinetics in vivo is imperative to ensure successful ...individualized treatment plans. Current standards for receptor analysis are performed on extracted tissues. These measurements are static and often physiologically irrelevant; therefore, only a partial picture of available receptors for drug targeting in vivo is provided. Until recently, in vivo measurements were limited by the inability to separate delivery, binding, and retention effects, but this can be circumvented by a dual-tracer approach for referencing the detected signal. We hypothesized that in vivo receptor concentration imaging (RCI) would be superior to ex vivo immunohistochemistry (IHC). Using multiple xenograft tumor models with varying EGFR expression, we determined the EGFR concentration in each model using a novel targeted agent (anti-EGFR affibody-IRDye800CW conjugate) along with a simultaneously delivered reference agent (control affibody-IRDye680RD conjugate). The RCI-calculated in vivo receptor concentration was strongly correlated with ex vivo pathologist-scored IHC and computer-quantified ex vivo immunofluorescence. In contrast, no correlation was observed with ex vivo Western blot analysis or in vitro flow-cytometry assays. Overall, our results argue that in vivo RCI provides a robust measure of receptor expression equivalent to ex vivo immunostaining, with implications for use in noninvasive monitoring of therapy or therapeutic guidance during surgery.
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