Revealing patient-reported experiences in healthcare from social media using thedesign-acquire-process-model-analyse-visualise framework.

Understanding patient experience in healthcare is increasingly important and desired by medical professionals in a patient-centred care approach. Healthcare discourse on social media presents an opportunity to gain a unique perspective on patient-reported experiences, complementing traditional survey data. These social media reports often appear as first-hand accounts of patients' journeys through the healthcare system, whose details extend beyond the confines of structured surveys and at a far larger scale than focus groups. However, in contrast with the vast presence of patient-experience data on social media and the potential benefits the data offers, it attracts comparatively little research attention due to the technical proficiency required for text analysis. In this article, we introduce the design-acquire-process-model-analyse-visualise framework to provide an overview of techniques and an approach to capture patient-reported experiences from social media data. We apply this framework in a case study on prostate cancer data from /r/ProstateCancer, demonstrate the framework's value in capturing specific aspects of patient concern (such as sexual dysfunction), provide an overview of the discourse, and show narrative and emotional progression through these stories. We anticipate this framework to apply to a wide variety of areas in healthcare, including capturing and differentiating experiences across minority groups, geographic boundaries, and types of illnesses.

Cases of trisomy 21 and trisomy 18 among historic and prehistoric individuals discovered from ancient DNA.

Aneuploidies, and in particular, trisomies represent the most common genetic aberrations observed in human genetics today. To explore the presence of trisomies in historic and prehistoric populations we screen nearly 10,000 ancient human individuals for the presence of three copies of any of the target autosomes. We find clear genetic evidence for six cases of trisomy 21 (Down syndrome) and one case of trisomy 18 (Edwards syndrome), and all cases are present in infant or perinatal burials. We perform comparative osteological examinations of the skeletal remains and find overlapping skeletal markers, many of which are consistent with these syndromes. Interestingly, three cases of trisomy 21, and the case of trisomy 18 were detected in two contemporaneous sites in early Iron Age Spain (800-400 BCE), potentially suggesting a higher frequency of burials of trisomy carriers in those societies. Notably, the care with which the burials were conducted, and the items found with these individuals indicate that ancient societies likely acknowledged these individuals with trisomy 18 and 21 as members of their communities, from the perspective of burial practice.

Extensive pedigrees reveal the social organization of a Neolithic community.

Social anthropology and ethnographic studies have described kinship systems and networks of contact and exchange in extant populations1-4. However, for prehistoric societies, these systems can be studied only indirectly from biological and cultural remains. Stable isotope data, sex and age at death can provide insights into the demographic structure of a burial community and identify local versus non-local childhood signatures, archaeogenetic data can reconstruct the biological relationships between individuals, which enables the reconstruction of pedigrees, and combined evidence informs on kinship practices and residence patterns in prehistoric societies. Here we report ancient DNA, strontium isotope and contextual data from more than 100 individuals from the site Gurgy 'les Noisats' (France), dated to the western European Neolithic around 4850-4500 BC. We find that this burial community was genetically connected by two main pedigrees, spanning seven generations, that were patrilocal and patrilineal, with evidence for female exogamy and exchange with genetically close neighbouring groups. The microdemographic structure of individuals linked and unlinked to the pedigrees reveals additional information about the social structure, living conditions and site occupation. The absence of half-siblings and the high number of adult full siblings suggest that there were stable health conditions and a supportive social network, facilitating high fertility and low mortality5. Age-structure differences and strontium isotope results by generation indicate that the site was used for just a few decades, providing new insights into shifting sedentary farming practices during the European Neolithic.

Advanced statistics identification of participant and treatment predictors associated with severe adverse effects induced by fluoropyrimidine-based chemotherapy.

PURPOSE: Adverse effects following fluoropyrimidine-based chemotherapy regimens are common. However, there are no current accepted diagnostic markers for prediction prior to treatment, and the underlying mechanisms remain unclear. This study aimed to determine genetic and non-genetic predictors of adverse effects. METHODS: Genomic DNA was analyzed for 25 single nucleotide polymorphisms (SNPs). Demographics, comorbidities, cancer and fluoropyrimidine-based chemotherapy regimen types, and adverse effect data were obtained from clinical records for 155 Australian White participants. Associations were determined by bivariate analysis, logistic regression modeling and Bayesian network analysis. RESULTS: Twelve different adverse effects were observed in the participants, the most common severe adverse effect was diarrhea (12.9%). Bivariate analysis revealed associations between all adverse effects except neutropenia, between genetic and non-genetic predictors, and between 8 genetic and 12 non-genetic predictors with more than 1 adverse effect. Logistic regression modeling of adverse effects revealed a greater/sole role for six genetic predictors in overall gastrointestinal toxicity, nausea and/or vomiting, constipation, and neutropenia, and for nine non-genetic predictors in diarrhea, mucositis, neuropathy, generalized pain, hand-foot syndrome, skin toxicity, cardiotoxicity and fatigue. The Bayesian network analysis revealed less directly associated predictors (one genetic and six non-genetic) with adverse effects and confirmed associations between six adverse effects, eight genetic predictors and nine non-genetic predictors. CONCLUSION: This study is the first to link both genetic and non-genetic predictors with adverse effects following fluoropyrimidine-based chemotherapy. Collectively, we report a wealth of information that warrants further investigation to elucidate the clinical significance, especially associations with genetic predictors and adverse effects.

Admixture has obscured signals of historical hard sweeps in humans.

The role of natural selection in shaping biological diversity is an area of intense interest in modern biology. To date, studies of positive selection have primarily relied on genomic datasets from contemporary populations, which are susceptible to confounding factors associated with complex and often unknown aspects of population history. In particular, admixture between diverged populations can distort or hide prior selection events in modern genomes, though this process is not explicitly accounted for in most selection studies despite its apparent ubiquity in humans and other species. Through analyses of ancient and modern human genomes, we show that previously reported Holocene-era admixture has masked more than 50 historic hard sweeps in modern European genomes. Our results imply that this canonical mode of selection has probably been underappreciated in the evolutionary history of humans and suggest that our current understanding of the tempo and mode of selection in natural populations may be inaccurate.

A multivariate extension to the standard 4σ criterion for comparison of forensic glass evidence.

This manuscript presents a more accurate and easy to implement multivariate generalisation of the international standard 4σ forensic glass comparison technique. Many crimes result in glass breaking, and the broken glass found at a crime scene can be important forensic evidence. The chemical composition of this glass can be measured to establish whether it can be distinguished from glass fragments found on a suspect's clothing. The chemical composition can be measured using laser ablation-inductively coupled plasma mass spectrometry. A commonly used method to compare fragments of glass is the 4σ interval criterion. This method, however, compares each element individually and does not take advantage of the multivariate nature of this data. We introduce a multivariate extension to this method, which makes use of the correlation structure between the elements. We demonstrate that this method results in an improvement in the false positive rate, with only a small compromise in the false negative rate. The improvement in false positive rate is desirable as false positives translate to misleading evidence against a potentially innocent defendant. The multivariate generalisation improves accuracy while retaining a similar interpretation, and so is suitable to present in court.

A simulated comparison of behavioural observation sampling methods.

Behavioural research requires the use of sampling methods to document the occurrence of responses observed. Sampling/recording methods include ad libitum, continuous, pinpoint (instantaneous), and one-zero (interval) sampling. Researchers have questioned the utility of each sampling method under different contexts. Our study compared computerized simulations of both pinpoint and one-zero sampling to continuous recordings. Two separate computer simulations were generated, one for response frequency and one for response duration, with three different response frequencies (high, medium, or low) and response durations (short, medium, and long) in each simulation, respectively. Similarly, three different observation intervals (5, 50, and 500 s) were used to record responses as both pinpoint and one-zero sampling methods in the simulations. Under both simulations, pinpoint sampling outperformed one-zero sampling, with pinpoint sampling producing less statistical bias in error rates under all frequencies, durations, and observation intervals. As observation intervals increased, both mean error rates and variability in error rates increased for one-zero sampling, while only variability in error rate increased for pinpoint sampling. The results suggest that pinpoint sampling techniques are effective for measuring both frequency (event) and duration (state) behaviours, and that pinpoint sampling is a less statistically biased behavioural observation method than one-zero sampling.

Associations of Immune Genetic Variability with Gulf War Illness in 1990-1991 Gulf War Veterans from the Gulf War Illness Consortium (GWIC) Multisite Case-Control Study.

Gulf War illness (GWI) encompasses a constellation of persistent debilitating symptoms associated with significant changes in central nervous system (CNS) and immune functioning. Currently, there is no validated biomarker for GWI risk susceptibility. Given the impact of immune responses linked to GWI symptomology, genetic variability that causes persistent inflammatory/immune alterations may be key. This Boston University-based Gulf War Illness Consortium (GWIC) study investigated the impact of single nucleotide polymorphisms (SNPs) in variants of immune and pain genetic markers IL1B, IL2, IL6, IL6R, IL10, TNF, TGF, TLR2, TLR4, MD2, MYD88, BDNF, CRP, ICE, COMT and OPRM1 on GWI occurrence in a Caucasian subset of Gulf War (GW) veterans with (cases, n = 170) and without (controls, n = 34) GWI. Logistic regression modeling created a prediction model of GWI risk that associated genetic variability in TGF (rs1800469, p = 0.009), IL6R (rs8192284, p = 0.004) and TLR4 (rs4986791, p = 0.013) with GWI occurrence. This prediction model was specific and sensitive, with a receiver operator characteristic area under the curve of 71.4%. This is the first report of immune genetic variability being predictive of GWI and warrants validation in larger independent cohorts. Future reports will present interactions of these genetic risk factors with other characteristics of GW service.

Is YouTube promoting the exotic pet trade? Analysis of the global public perception of popular YouTube videos featuring threatened exotic animals.

The exploitation of threatened exotic species via social media challenges efforts to regulate the exotic pet trade and consequently threatens species conservation. To investigate how such content is perceived by the global community, mixed model sentiment analysis techniques were employed to explore variations in attitudes expressed through text and emoji usage in public comments associated with 346 popular YouTube® videos starring exotic wild cats or primates in 'free handling' situations. Negative interactions between wild cats and primates with other species were found to be associated with both text and emoji median sentiment reduction, however were still accompanied by a median emoji sentiment above zero. Additionally, although a negative trend in median text sentiment was observed in 2015 for primates, an otherwise consistent positive median text and emoji sentiment score through time across all IUCN Red List categories was revealed in response to both exotic wild cat and primate videos, further implying the societal normalisation and acceptance of exotic pets. These findings highlight the urgency for effective YouTube® policy changes and content management to promote public education and conservation awareness, whilst extinguishing false legitimisation and demand for the exotic pet trade.

Widespread Denisovan ancestry in Island Southeast Asia but no evidence of substantial super-archaic hominin admixture.

The hominin fossil record of Island Southeast Asia (ISEA) indicates that at least two endemic 'super-archaic' species-Homo luzonensis and H. floresiensis-were present around the time anatomically modern humans arrived in the region >50,000 years ago. Intriguingly, contemporary human populations across ISEA carry distinct genomic traces of ancient interbreeding events with Denisovans-a separate hominin lineage that currently lacks a fossil record in ISEA. To query this apparent disparity between fossil and genetic evidence, we performed a comprehensive search for super-archaic introgression in >400 modern human genomes, including >200 from ISEA. Our results corroborate widespread Denisovan ancestry in ISEA populations, but fail to detect any substantial super-archaic admixture signals compatible with the endemic fossil record of ISEA. We discuss the implications of our findings for the understanding of hominin history in ISEA, including future research directions that might help to unlock more details about the prehistory of the enigmatic Denisovans.

Tacrolimus dose, blood concentrations and acute nephrotoxicity, but not CYP3A5/ABCB1 genetics, are associated with allograft tacrolimus concentrations in renal transplant recipients.

AIMS: Long-term use of the immunosuppressant tacrolimus is limited by nephrotoxicity. Following renal transplantation, the risk of nephrotoxicity may be determined more by allograft than by blood tacrolimus concentrations, and thus may be affected by donor CYP3A5 and ABCB1 genetics. Little is known regarding factors that determine tacrolimus intrarenal exposure. METHODS: This study investigated the relationship between trough blood (C0Blood ) and allograft (CGraft ) tacrolimus concentrations and tacrolimus dose, haematocrit, genetics, acute nephrotoxicity, rejection status, delayed graft function, and time post-transplant. C0Blood and CGraft were quantified in 132 renal transplant recipients together with recipient and donor CYP3A5 (rs776746) and ABCB1 3435 (rs1045642) genotypes. RESULTS: C0Blood ranged from 2.6 to 52.3 ng/mL and CGraft from 33 to 828 pg/mg tissue. Adjusting for dose, recipients who were CYP3A5 expressors had lower C0Blood compared to nonexpressors, whilst delayed graft function was associated with higher C0Blood . Linear regression showed that the significant predictors of CGraft were C0Blood (point-wise P = 7 × 10-10 ), dose (P = .004) acute nephrotoxicity (P = .002) and an interaction between C0Blood and acute tacrolimus nephrotoxicity (P = .0002), with an adjusted r2  = 0.35 and no contribution from donor or recipient CYP3A5 or ABCB1 genotype. The association between CGraft and acute nephrotoxicity depended on one very high CGraft (828 pg/mg tissue). CONCLUSIONS: Recipient and donor CYP3A5 and ABCB1 3435C>T genotypes are not determinants of allograft tacrolimus exposure in kidney transplant recipients. However, tacrolimus dose and C0Blood were significant predictors of CGraft , and the relationship between C0Blood and CGraft appeared to differ in the presence or absence of acute nephrotoxicity.

Uptake and Glycosylation of Smoke-Derived Volatile Phenols by Cabernet Sauvignon Grapes and Their Subsequent Fate during Winemaking.

Wine made from grapes exposed to bushfire smoke can exhibit unpleasant smoky, ashy characters, which have been attributed to the presence of smoke-derived volatile phenols, in free or glycosylated forms. Here we report the uptake and glycosylation of volatile phenols by grapes following exposure of Cabernet Sauvignon vines to smoke, and their fate during winemaking. A significant delay was observed in the conversion of volatile phenols to their corresponding glycoconjugates, which suggests sequestration, the presence of intermediates within the glycosylation pathway and/or other volatile phenol storage forms. This finding has implications for industry in terms of detecting smoke-affected grapes following vineyard smoke exposure. The potential for an in-canopy sprinkler system to mitigate the uptake of smoke-derived volatile phenols by grapes, by spraying grapevines with water during smoke exposure, was also evaluated. While "misting" appeared to partially mitigate the uptake of volatile phenols by grapes during grapevine exposure to smoke, it did not readily influence the concentration of volatile phenols or the sensory perception of smoke taint in wine. Commercial sensors were used to monitor the concentration of smoke particulate matter (PM) during grapevine exposure to low and high density smoke. Similar PM profiles were observed, irrespective of smoke density, such that PM concentrations did not reflect the extent of smoke exposure by grapes or risk of taint in wine. The sensors could nevertheless be used to monitor the presence of smoke in vineyards during bushfires, and hence, the need for compositional analysis of grapes to quantify smoke taint marker compounds.

Mental Health Disease or Preventable Problem? Australian Dog Trainers' Opinions about Canine Separation Anxiety Differ with Training Style.

Separation anxiety is common. Many dog owners do not seek help from a veterinarian but might consult a trainer. The objective of this study was to investigate Australian trainers' opinions about separation anxiety. An online survey was distributed via training organisations, resulting in 63 completed surveys. Descriptive statistics and Fisher's exact tests were applied. Respondents were grouped into reward-based (n = 41) and balanced (n = 22) trainers. Most trainers (82.5%) used multiple methods to identify separation anxiety but only 7.9% referred to a veterinarian for diagnosis. Reward-based trainers ranked assistance from a veterinarian and owner's willingness to try medication as more important than balanced trainers (p < 0.05). More balanced trainers reported that medication was rarely necessary in the cases they saw: 50% balanced compared with 4.9% reward-based trainers, with 95% CIs of [28.2, 71.8] and [0.6, 16.5], respectively. Almost all (95.5%) balanced trainers believed separation anxiety was preventable compared with 52.6% of reward-based trainers (p < 0.05). We conclude that opinions about separation anxiety varied between reward-based and balanced trainers. Trainers are not taught, expected, or legally allowed to diagnose anxiety disorders. This study showed that balanced trainers were less likely to recommend involvement of veterinarians who can make a diagnosis and rule out other causes of observed behaviours.

Long-term outcome of kidney transplant by using restored kidney grafts after tumour ex vivo excision - a prospective study.

The aim of this study is to report long-term outcomes of kidney transplantation by using the kidney graft after a small tumour ex vivo excision. A structured programme was established to use the restored kidney graft from urological referral after radical nephrectomy. The criteria were defined as tumour size ≤3 cm, margin clear on frozen section and recipients aged ≥60 years or those on the urgent list for transplantation as a result of imminent lack of dialysis access. The recipients were followed up regularly for surveillance of tumour recurrence. Between February 2007 and February 2018, 28 recipients had kidney transplantation by using the restored kidney grafts. The tumour size was 2.6 ± 0.7 cm. The follow-up was median 7 years without evidence of tumour recurrence. The patient and graft survival was satisfactory. Kidney transplantation by using restored kidneys after a small tumour excision is a novel source for selected recipients. The long-term patient and graft survival is satisfactory. Although there is a risk of tumour recurrence, it is rare event. Together with literature review, we would support use of kidney graft after a small tumour excision for selected recipients.

Influence of partial dealcoholization on the composition and sensory properties of Cabernet Sauvignon wines.

Worldwide, winemakers are increasingly adopting alcohol management strategies to counter the higher wine ethanol concentrations observed over the past ~30 years. Wines with high ethanol levels exhibit increased 'hotness' on the palate, which is generally considered to negatively impact wine quality. This study investigated changes in the chemical and sensory profiles of five Cabernet Sauvignon wines following their partial dealcoholization by reverse osmosis-evaporative perstraction (RO-EP). Descriptive analysis (DA) of wine before and after RO-EP treatment indicated dealcoholization did not strongly affect wine aroma and flavor, consistent with the small changes observed in wine chemical composition. However, significant differences in the perception of wine palate attributes were observed, with dealcoholized wines found to exhibit lower acidity, sweetness, bitterness, saltiness and/or body. Astringency was enhanced following partial dealcoholization of one wine, but diminished in another. Sensory trials were also undertaken to determine the optimal ethanol concentration of wines, or the 'alcohol sweetspot'. Two approaches to alcohol sweetspotting of dealcoholized wines were evaluated, together with two methods of statistical analysis, chi-squared goodness of fit and one proportion tests.

Regulatory Compliance in Online Dog Advertisements in Australia.

In Australia, each state and territory authority implements and enforces regulations regarding dog management-including the breeding and sale of dogs online-which is increasingly becoming the most popular method of obtaining pets. The aims for this study included: 1. Benchmarking regulatory compliance in online dog advertisements in Australia, and, 2. Understanding factors associated with regulatory compliance in online advertisements. We collected advertisements for dogs and puppies from Gumtree-one of Australia's most popular online trading platforms - on two separate days, two weeks apart (25 March and 8 April 2019). A total of 1735 unique advertisements were included in the dataset. Chi-squared tests and multivariable logistic regression models were used to identify risk factors for microchipping, desexing and breeder identification number, and compliance levels. State laws requiring animals to be microchipped prior to sale and the inclusion of chip numbers in advertisements were found to be the biggest factor in increasing likelihood of microchipped animals in Gumtree advertisements, while desexing was more common in microchipped and older animals. The online ad was more likely to include a breeder ID if the dog was young, vaccinated, and advertised by a breeder rather than an owner. The findings from this study will assist regulators to make evidence-based decisions on managing online advertisements for companion animals. In the future, the benchmarking this study has presented will allow future analysis of the effectiveness of regulation changes.

GHOST: Recovering Historical Signal from Heterotachously Evolved Sequence Alignments.

Molecular sequence data that have evolved under the influence of heterotachous evolutionary processes are known to mislead phylogenetic inference. We introduce the General Heterogeneous evolution On a Single Topology (GHOST) model of sequence evolution, implemented under a maximum-likelihood framework in the phylogenetic program IQ-TREE (http://www.iqtree.org). Simulations show that using the GHOST model, IQ-TREE can accurately recover the tree topology, branch lengths, and substitution model parameters from heterotachously evolved sequences. We investigate the performance of the GHOST model on empirical data by sampling phylogenomic alignments of varying lengths from a plastome alignment. We then carry out inference under the GHOST model on a phylogenomic data set composed of 248 genes from 16 taxa, where we find the GHOST model concurs with the currently accepted view, placing turtles as a sister lineage of archosaurs, in contrast to results obtained using traditional variable rates-across-sites models. Finally, we apply the model to a data set composed of a sodium channel gene of 11 fish taxa, finding that the GHOST model is able to elucidate a subtle component of the historical signal, linked to the previously established convergent evolution of the electric organ in two geographically distinct lineages of electric fish. We compare inference under the GHOST model to partitioning by codon position and show that, owing to the minimization of model constraints, the GHOST model offers unique biological insights when applied to empirical data.

Investigating Alcohol Sweetspot Phenomena in Reduced Alcohol Red Wines.

Warmer growing seasons, variations to grape ripening dynamics, and stylistic changes have contributed to increased wine alcohol levels, which can negatively impact sensory properties. As a consequence, winemakers have sought technological innovations to produce reduced alcohol wine (RAW). The sensory methodology used by industry to optimize the ethanol content of RAW is known as 'alcohol sweetspotting'. However, to date, there is no scientific evidence to support the alcohol sweetspot phenomenon, and the sensory methodology used for alcohol sweetspotting has not been validated. In this study, different methods of presenting wine samples (i.e., ordered vs. randomized, and linear vs. circular) were employed to determine to what extent presentation order influences the outcome of alcohol sweetspotting trials. Two different approaches to statistical analysis of sensory data, i.e., chi-square goodness of fit vs. one proportion tests, were also evaluated. Statistical analyses confirmed alcohol sweetspots were apparent in some sweetspot determination trials, but outcomes were not reproducible in replicate determinations (either by panel or by individual panelists). Analysis of data using the one proportion test improved the likelihood of identifying statistically significant differences between RAWs, but variation in individuals' sensitivity to differences in sensory properties following ethanol removal prevented validation of the alcohol sweetspot phenomenon based on the wines studied.

The impact of liver transplant recipient and donor genetic variability on tacrolimus exposure and transplant outcome.

This study investigated the effect of recipient and donor genetic variability on dose-adjusted steady-state tacrolimus concentrations (Css ) and clinical outcomes 3 and 6 months after liver transplant. Twenty-nine recipients and matched donor blood samples were genotyped for 27 single nucleotide polymorphisms including CYP3A5*3 (rs776746), ABCB1 haplotype and immune genes. Associations between genetic variability and clinical parameters and Css and the occurrence of rejection and nephrotoxicity were analysed by multivariate and multinomial logistic regression modelling and Jonckheere-Terpstra tests examined the impact of combined donor/recipient CYP3A5 expression on Css . At 3 months post-transplant modelling revealed an association between tacrolimus Css and recipient CASP1 rs580523 genotype (P = 0.005), accounting for 52% Css variance. Jonckheere-Terpstra tests revealed that as combined donor/recipient CYP3A5 expression increased, Css decreased (P = 0.010 [3 months], 0.018 [6 months]). As this is the first report of CASP1 genetic variability influencing tacrolimus Css , further validation in larger cohorts is required.

Relationship between allograft cyclosporin concentrations and P-glycoprotein expression in the 1st month following renal transplantation.

The immunosuppressant cyclosporin is a P-glycoprotein (P-gp) substrate whose impaired function has been associated with an increased risk of cyclosporin-induced nephrotoxicity following renal transplantation. This study investigated the relationship between blood and allograft cyclosporin concentration, and the effect of P-gp expression. Fifty biopsy samples were obtained from 39 renal transplant recipients who received cyclosporin as part of maintenance immunosuppression. Blood cyclosporin concentrations (2 hours postdose) were obtained from clinical records, matching allograft cyclosporin concentrations were measured in frozen biopsy tissue by liquid chromatography-tandem mass spectrometry, and allograft P-gp expression was assessed by immunohistochemistry. Blood and allograft cyclosporin concentrations in the 1st month post-transplantation ranged from 505-2005 µg/L and 0.01-16.7 ng/mg tissue, respectively. Dose was the only significant predictor of allograft cyclosporin concentrations (adjusted R2  = .24, F-statistic = 11.52, P = .0019), with no effect of P-gp expression or blood cyclosporin concentrations. P-gp expression is not the major determinant of allograft cyclosporin concentrations.