Chemotherapy-Response Monitoring of Breast Cancer Patients Using Quantitative Ultrasound-Based Intra-Tumour Heterogeneities

© 2017 The Author(s). Anti-cancer therapies including chemotherapy aim to induce tumour cell death. Cell death introduces alterations in cell morphology and tissue micro-structures that cause measurable changes in tissue echogenicity. This study investigated the effectiveness of quantitative ultrasound (QUS) parametric imaging to characterize intra-tumour heterogeneity and monitor the pathological response of breast cancer to chemotherapy in a large cohort of patients (n = 100). Results demonstrated that QUS imaging can non-invasively monitor pathological response and outcome of breast cancer patients to chemotherapy early following treatment initiation. Specifically, QUS biomarkers quantifying spatial heterogeneities in size, concentration and spacing of acoustic scatterers could predict treatment responses of patients with cross-validated accuracies of 82 ± 0.7%, 86 ± 0.7% and 85 ± 0.9% and areas under the receiver operating characteristic (ROC) curve of 0.75 ± 0.1, 0.80 ± 0.1 and 0.89 ± 0.1 at 1, 4 and 8 weeks after the start of treatment, respectively. The patients classified as responders and non-responders using QUS biomarkers demonstrated significantly different survivals, in good agreement with clinical and pathological endpoints. The results form a basis for using early predictive information on survival-linked patient response to facilitate adapting standard anti-cancer treatments on an individual patient basis

Prevalence of asthma, aspirin sensitivity and allergy in chronic rhinosinusitis: data from the UK National Chronic Rhinosinusitis Epidemiology Study

Background: Chronic rhinosinusitis (CRS) is a common disorder associated with other respiratory tract diseases such as asthma and inhalant allergy. However, the prevalence of these co-morbidities varies considerably in the existing medical literature and by phenotype of CRS studied. The study objective was to identify the prevalence of asthma, inhalant allergy and aspirin sensitivity in CRS patients referred to secondary care and establish any differences between CRS phenotypes. Methods: All participants were diagnosed in secondary care according to international guidelines and invited to complete a questionnaire including details of co-morbidities and allergies. Data were analysed for differences between controls and CRS participants and between phenotypes using chi-squared tests. Results: The final analysis included 1470 study participants: 221 controls, 553 CRS without nasal polyps (CRSsNPs), 651 CRS with nasal polyps (CRSwNPs) and 45 allergic fungal rhinosinusitis (AFRS). The prevalence of asthma was 9.95, 21.16, 46.9 and 73.3% respectively. The prevalence of self-reported confirmed inhalant allergy was 13.1, 20.3, 31.0 and 33.3% respectively; house dust mite allergy was significantly higher in CRSwNPs (16%) compared to CRSsNPs (9%, p < 0.001). The prevalence of self- reported aspirin sensitivity was 2.26, 3.25, 9.61 and 40% respectively. The odds ratio for aspirin sensitivity amongst those with AFRS was 28.8 (CIs 9.9, 83.8) p < 0.001. Conclusions: The prevalence of asthma and allergy in CRS varies by phenoytype, with CRSwNPs and AFRS having a stronger association with both. Aspirin sensitivity has a highly significant association with AFRS. All of these comorbidities are significantly more prevalent than in non-CRS controls and strengthen the need for a more individualised approach to the combined airway

Bengali translation and characterisation of four cognitive and trait measures for autism spectrum conditions in India

Background Autism is characterised by atypical social-communicative behaviour and restricted range of interests and repetitive behaviours. These features exist in a continuum in the general population. Behavioural measures validated across cultures and languages are required to quantify the dimensional traits of autism in these social and non-social domains. Bengali is the seventh most spoken language in the world. However, there is a serious dearth of data on standard measures of autism-related social and visual cognition in Bengali. Methods Bengali translations of two measures related to social-communicative functioning (the Children’s Reading the Mind in the Eyes Test (RMET) and a facial emotion recognition test with stimuli taken from the Karolinska Directed Emotional Faces database), one measure of visual perceptual disembedding (the Embedded Figures Test), and a questionnaire measure (the Children’s Empathy Quotient) were tested in 25 children with autism spectrum conditions (ASC) and 26 control children (mean age = 10.7 years) in Kolkata, India. Group differences were analysed by t test and multiple regression (after accounting for potential effects of gender, IQ, and age). Results Behavioural and trait measures were associated with group differences in the expected directions: ASC children scored lower on the Children’s Empathy Quotient and the RMET, as well as on facial emotion recognition, but were faster and more accurate on the Embedded Figures Test. Distributional properties of these measures within groups are similar to those reported in Western countries. Conclusions These results provide an empirical demonstration of cross-cultural generalisability and applicability of these standard behavioural and trait measures related to autism, in a major world language

Glucuronidation by UGT1A1 Is the Dominant Pathway of the Metabolic Disposition of Belinostat in Liver Cancer Patients

10.1371/journal.pone.0054522PLoS ONE81

Trends in upper gastrointestinal diagnosis over four decades in Lusaka, Zambia: a retrospective analysis of endoscopic findings

BACKGROUND AND AIMS: There a shortage of robust information about profiles of gastrointestinal disease in sub-Saharan Africa. The endoscopy unit of the University Teaching Hospital in Lusaka has been running without interruption since 1977 and this 38-year record is largely intact. We report an analysis of endoscopic findings over this period. METHODS: Written endoscopy records from 29th September 1977 to 16th December 2014 were recovered, computerised, coded by two experienced endoscopists and analysed. Temporal trends were analysed using tables, graphs, and unconditional logistic regression, with age, sex of patient, decade, and endoscopist as independent variables to adjust for inter-observer variation. RESULTS: Sixteen thousand nine hundred fifty-three records were identified and analysed. Diagnosis of gastric ulcer rose by 22 %, and that of duodenal ulcer fell by 14 % per decade. Endoscopically diagnosed oesophageal cancer increased by 32 % per decade, but gastric cancer rose only in patients under 60 years of age (21 % per decade). Oesophageal varices were the commonest finding in patients presenting with haematemesis, increasing by 14 % per decade in that patient group. Two HIV-related diagnoses, oesophageal candidiasis and Kaposi’s sarcoma, rose from almost zero to very high levels in the 1990s but fell substantially after 2005 when anti-retroviral therapy became widely available. CONCLUSIONS: This useful dataset suggests that there are important trends in some endoscopic findings over four decades. These trends are not explained by inter-observer variation. Reasons for the divergent trends in incidence of peptic ulceration and apparent trends in diagnosis of upper gastrointestinal cancers merit further exploration

Study of hadronic event-shape variables in multijet final states in pp collisions at √s=7 TeV

Peer reviewe

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

Constraints on parton distribution functions and extraction of the strong coupling constant from the inclusive jet cross section in pp collisions at √s=7 TeV

Peer reviewe

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

A module-based analytical strategy to identify novel disease-associated genes shows an inhibitory role for interleukin 7 Receptor in allergic inflammation

<p>Abstract</p> <p>Background</p> <p>The identification of novel genes by high-throughput studies of complex diseases is complicated by the large number of potential genes. However, since disease-associated genes tend to interact, one solution is to arrange them in modules based on co-expression data and known gene interactions. The hypothesis of this study was that such a module could be a) found and validated in allergic disease and b) used to find and validate one ore more novel disease-associated genes.</p> <p>Results</p> <p>To test these hypotheses integrated analysis of a large number of gene expression microarray experiments from different forms of allergy was performed. This led to the identification of an experimentally validated reference gene that was used to construct a module of co-expressed and interacting genes. This module was validated in an independent material, by replicating the expression changes in allergen-challenged CD4⁺cells. Moreover, the changes were reversed following treatment with corticosteroids. The module contained several novel disease-associated genes, of which the one with the highest number of interactions with known disease genes, <it>IL7R</it>, was selected for further validation. The expression levels of <it>IL7R </it>in allergen challenged CD4⁺cells decreased following challenge but increased after treatment. This suggested an inhibitory role, which was confirmed by functional studies.</p> <p>Conclusion</p> <p>We propose that a module-based analytical strategy is generally applicable to find novel genes in complex diseases.</p