Technological Innovations for the Human Service Profession

Many professions are incorporating innovative and affordable technologies such as smart phones, wireless Internet, gaming systems in which the only controller is the human body, and countless software programs and applications to improve efficiency, increase access, and promote themselves. The human service profession is also making strides to utilize new and existing technological mediums in original and creative ways. The article presents ideas for the use of innovative technological approaches in the training of human services students, the dissemination of services to consumers, supervision of human service students and professions, and the everyday operations of human service agencies. The limitations of using technological mediums will also be discussed

Single-cell characterization of leukemic and non-leukemic immune repertoires in CD8(+) T-cell large granular lymphocytic leukemia

T cell large granular lymphocytic leukemia (T-LGLL) is a rare lymphoproliferative disorder of mature, clonally expanded T cells, where somatic-activating STAT3 mutations are common. Although T-LGLL has been described as a chronic T cell response to an antigen, the function of the non-leukemic immune system in this response is largely uncharacterized. Here, by utilizing single-cell RNA and T cell receptor profiling (scRNA+TCR alpha beta-seq), we show that irrespective of STAT3 mutation status, T-LGLL clonotypes are more cytotoxic and exhausted than healthy reactive clonotypes. In addition, T-LGLL clonotypes show more active cell communication than reactive clones with non-leukemic immune cells via costimulatory cell-cell interactions, monocyte-secreted proinflammatory cytokines, and T-LGLL-clone-secreted IFN gamma. Besides the leukemic repertoire, the non-leukemic T cell repertoire in T-LGLL is also more mature, cytotoxic, and clonally restricted than in other cancers and autoimmune disorders. Finally, 72% of the leukemic T-LGLL clonotypes share T cell receptor similarities with their non-leukemic repertoire, linking the leukemic and non-leukemic repertoires together via possible common target antigens. Our results provide a rationale to prioritize therapies that target the entire immune repertoire and not only the T-LGLL clonotype. T cell large granular lymphocytic leukemia (T-LGLL) is a lymphoproliferative disorder involving clonally expanded T cell clones and is not fully understood. Here the authors show that the rest of the immune repertoire is interconnected with the T-LGLL clonotype(s) and is more mature, cytotoxic and clonally restricted than in other cancers and autoimmune disorders.Peer reviewe

Identification of glucocorticoid-related molecular signature by whole blood methylome analysis

Objective Cushing's syndrome represents a state of excessive glucocorticoids related to glucocorticoid treatments or to endogenous hypercortisolism. Cushing's syndrome is associated with high morbidity, with significant inter-individual variability. Likewise, adrenal insufficiency is a life-threatening condition of cortisol deprivation. Currently, hormone assays contribute to identify Cushing's syndrome or adrenal insufficiency. However, no biomarker directly quantifies the biological glucocorticoid action. The aim of this study was to identify such markers. Design We evaluated whole blood DNA methylome in 94 samples obtained from patients with different glucocorticoid states (Cushing's syndrome, eucortisolism, adrenal insufficiency). We used an independent cohort of 91 samples for validation. Methods Leukocyte DNA was obtained from whole blood samples. Methylome was determined using the Illumina methylation chip array (~850 000 CpG sites). Both unsupervised (principal component analysis) and supervised (Limma) methods were used to explore methylome profiles. A Lasso-penalized regression was used to select optimal discriminating features. Results Whole blood methylation profile was able to discriminate samples by their glucocorticoid status: glucocorticoid excess was associated with DNA hypomethylation, recovering within months after Cushing's syndrome correction. In Cushing's syndrome, an enrichment in hypomethylated CpG sites was observed in the region of FKBP5 gene locus. A methylation predictor of glucocorticoid excess was built on a training cohort and validated on two independent cohorts. Potential CpG sites associated with the risk for specific complications, such as glucocorticoid-related hypertension or osteoporosis, were identified, needing now to be confirmed on independent cohorts. Conclusions Whole blood DNA methylome is dynamically impacted by glucocorticoids. This biomarker could contribute to better assessment of glucocorticoid action beyond hormone assays

Evaluation of automated airway morphological quantification for assessing fibrosing lung disease

Abnormal airway dilatation, termed traction bronchiectasis, is a typical feature of idiopathic pulmonary fibrosis (IPF). Volumetric computed tomography (CT) imaging captures the loss of normal airway tapering in IPF. We postulated that automated quantification of airway abnormalities could provide estimates of IPF disease extent and severity. We propose AirQuant, an automated computational pipeline that systematically parcellates the airway tree into its lobes and generational branches from a deep learning based airway segmentation, deriving airway structural measures from chest CT. Importantly, AirQuant prevents the occurrence of spurious airway branches by thick wave propagation and removes loops in the airway-tree by graph search, overcoming limitations of existing airway skeletonisation algorithms. Tapering between airway segments (intertapering) and airway tortuosity computed by AirQuant were compared between 14 healthy participants and 14 IPF patients. Airway intertapering was significantly reduced in IPF patients, and airway tortuosity was significantly increased when compared to healthy controls. Differences were most marked in the lower lobes, conforming to the typical distribution of IPF-related damage. AirQuant is an open-source pipeline that avoids limitations of existing airway quantification algorithms and has clinical interpretability. Automated airway measurements may have potential as novel imaging biomarkers of IPF severity and disease extent

Effects of the Pelleting Process on Diet Formulations with Varying Levels of Crystalline Amino Acids and Reducing Sugars on Nursery Pig Growth Performance

Pelleting swine feed and the use of crystalline amino acids and by-product ingredients can potentially create ideal conditions that further facilitate the Maillard browning reaction. The Maillard reaction combines an amino group of a free amino acid and a carbonyl group of a reducing sugar (RS), making the amino acid less available. The objective of this study was to determine the effects of pelleting swine diets containing free amino acids and reducing sugars at high temperatures on nursery pig growth performance. A total of 360 pigs (initially 25.0 lb; Line 200 × 400; DNA, Columbus, NE) were used in a study evaluating the effect of crystalline AA, reducing sugars, and feed form on growth performance of nursery pigs. Treatments were arranged in a 2 × 2 × 2 factorial with main effects of crystalline AA concentration (low vs. high), reducing sugars (RS; low vs. high), and diet form (mash vs. pellet). Diets were formulated with low or high crystalline AA and low or high reducing sugars provided by co-product ingredients, DDGS and bakery meal. Diets were pelleted to a conditioning temperature of 187.5°F. When pigs weighed approximately 25 lb, they were weighed, and pens were randomly assigned treatments. There were 9 replications per treatment and 5 pigs per pen. There were no 3-way or 2-way interactions. For the main effect of form, there was no evidence of difference in ADG, and ADFI increased (P = 0.001) in pigs fed mash diets compared to pellets. Feed efficiency and caloric efficiency improved (P = 0.001) in pigs fed pelleted diets compared to mash diets. For the main effect of crystalline AA, there was no evidence of difference in ADG or F/G; however, pigs fed high crystalline AA had increased (P = 0.024) ADFI compared to those fed low crystalline AA diets. For the main effect of RS inclusion, pigs fed low RS diets had increased (P \u3c 0.041) ADG and ADFI compared to pigs fed high RS inclusion diets. There was an improvement (P = 0.019) in F/G and caloric efficiency for pigs fed high RS inclusion diets compared to those fed low RS diets. There was no evidence of difference in IOFC for form, crystalline AA, or RS. In conclusion, there was no evidence of interactions between diet types, indicating that increasing amounts of crystalline AA and RS did not increase the Maillard reaction or reduce growth performance when pelleting diets by using the reported conditions. Pigs fed pelleted diets had similar ADG and an 8% improvement in F/G compared to those fed mash diets. Pigs fed the high RS diets had reduced feed intake, which resulted in reduced gain and improved feed and caloric efficiency. Additionally, pigs fed high AA diets had increased feed intake

Whole blood methylome-derived features to discriminate endocrine hypertension

Background: Arterial hypertension represents a worldwide health burden and a major risk factor for cardiovascular morbidity and mortality. Hypertension can be primary (primary hypertension, PHT), or secondary to endocrine disorders (endocrine hypertension, EHT), such as Cushing's syndrome (CS), primary aldosteronism (PA), and pheochromocytoma/paraganglioma (PPGL). Diagnosis of EHT is currently based on hormone assays. Efficient detection remains challenging, but is crucial to properly orientate patients for diagnostic confirmation and specific treatment. More accurate biomarkers would help in the diagnostic pathway. We hypothesized that each type of endocrine hypertension could be associated with a specific blood DNA methylation signature, which could be used for disease discrimination. To identify such markers, we aimed at exploring the methylome profiles in a cohort of 255 patients with hypertension, either PHT (n = 42) or EHT (n = 213), and at identifying specific discriminating signatures using machine learning approaches. Results: Unsupervised classification of samples showed discrimination of PHT from EHT. CS patients clustered separately from all other patients, whereas PA and PPGL showed an overall overlap. Global methylation was decreased in the CS group compared to PHT. Supervised comparison with PHT identified differentially methylated CpG sites for each type of endocrine hypertension, showing a diffuse genomic location. Among the most differentially methylated genes, FKBP5 was identified in the CS group. Using four different machine learning methods—Lasso (Least Absolute Shrinkage and Selection Operator), Logistic Regression, Random Forest, and Support Vector Machine—predictive models for each type of endocrine hypertension were built on training cohorts (80% of samples for each hypertension type) and estimated on validation cohorts (20% of samples for each hypertension type). Balanced accuracies ranged from 0.55 to 0.74 for predicting EHT, 0.85 to 0.95 for predicting CS, 0.66 to 0.88 for predicting PA, and 0.70 to 0.83 for predicting PPGL. Conclusions: The blood DNA methylome can discriminate endocrine hypertension, with methylation signatures for each type of endocrine disorder

Single-cell characterization of leukemic and non-leukemic immune repertoires in CD8+ T-cell large granular lymphocytic leukemia

T cell large granular lymphocytic leukemia (T-LGLL) is a rare lymphoproliferative disorder of mature, clonally expanded T cells, where somatic-activating STAT3 mutations are common. Although T-LGLL has been described as a chronic T cell response to an antigen, the function of the non-leukemic immune system in this response is largely uncharacterized. Here, by utilizing single-cell RNA and T cell receptor profiling (scRNA+TCRαβ-seq), we show that irrespective of STAT3 mutation status, T-LGLL clonotypes are more cytotoxic and exhausted than healthy reactive clonotypes. In addition, T-LGLL clonotypes show more active cell communication than reactive clones with non-leukemic immune cells via costimulatory cell-cell interactions, monocyte-secreted proinflammatory cytokines, and T-LGLL-clone-secreted IFN gamma. Besides the leukemic repertoire, the non-leukemic T cell repertoire in T-LGLL is also more mature, cytotoxic, and clonally restricted than in other cancers and autoimmune disorders. Finally, 72% of the leukemic T-LGLL clonotypes share T cell receptor similarities with their non-leukemic repertoire, linking the leukemic and non-leukemic repertoires together via possible common target antigens. Our results provide a rationale to prioritize therapies that target the entire immune repertoire and not only the T-LGLL clonotype.</p

"It feels so good it almost hurts": Young adults' experiences of orgasm and sexual pleasure

Orgasm is a "goal" of much sexual activity, and a source of potentially intense pleasure and fulfillment, yet can be fraught with difficulty or distress. Relatively little social science research has explored people's experiences around, and their meanings related to, orgasm, and indeed other sexual pleasures, especially with young adults. This study aimed to provide a rich exploration of the meanings associated with orgasm and sexual pleasure during sex with a partner, to understand the social patterning of orgasm experience. A qualitative survey was used to collect data from 119 sexually experienced British young adults (81% women, mean age 20, 92% heterosexual). A descriptive form of thematic analysis that prioritizes participants' meanings and experiences was used to identify and explore patterns in the data. Five main themes are reported here: (a) orgasm: the purpose and end of sex; (b) "it's more about my partner's orgasm"; (c) orgasm: the ultimate pleasure?; (d) orgasm is not a simple physiological response; and (e) faking orgasm is not uncommon. These (mostly not gendered) themes demonstrate the complex and contradictory meanings around orgasm, and reveal meaning to be dependent on situation and context. However, they do resonate strongly with widespread discourses of sexuality that prioritize heterosexual coitus, orgasm, and orgasm reciprocity. © 2014 Copyright The Society for the Scientific Study of Sexuality