In-Scanner Thoughts shape Resting-state Functional Connectivity: how participants "rest" matters.

Resting-state fMRI (rs-fMRI) scans-namely those lacking experimentally-controlled stimuli or cognitive demands-are often used to identify aberrant patterns of functional connectivity (FC) in clinical populations. To minimize interpretational uncertainty, researchers control for across-cohort disparities in age, gender, co-morbidities, and head motion. Yet, studies rarely, if ever, consider the possibility that systematic differences in inner experience (i.e., what subjects think and feel during the scan) may directly affect FC measures. Here we demonstrate that is the case using a rs-fMRI dataset comprising 471 scans annotated with experiential data. Wide-spread significant differences in FC are observed between scans that systematically differ in terms of reported in-scanner experience. Additionally, we show that FC can successfully predict specific aspects of in-scanner experience in a manner similar to how it predicts demographics, cognitive abilities, clinical outcomes and labels. Together, these results highlight the key role of in-scanner experience in shaping rs-fMRI estimates of FC.

Brief Report: Risk of Recurrent Interstitial Lung Disease From Osimertinib Versus Erlotinib Rechallenge After Symptomatic Osimertinib-Induced Interstitial Lung Disease.

Introduction: Interstitial lung disease (ILD) is the most frequent cause of drug-related mortality from EGFR tyrosine kinase inhibitors (TKIs). Yet, for patients with symptomatic osimertinib-induced ILD, the risk of recurrent ILD associated with EGFR TKI rechallenge, either with osimertinib or another TKI, such as erlotinib, is unclear. Methods: Retrospective study of 913 patients who received osimertinib treatment for EGFR mutation-positive NSCLC. Clinical characteristics, ILD treatment history, and subsequent anticancer therapy of patients with symptomatic osimertinib-induced ILD were collated. The primary end point was to compare the incidence of recurrent ILD with osimertinib versus erlotinib rechallenge. Results: Of 913 patients, 35 (3.8%) had symptomatic osimertinib-induced ILD, of which 12 (34%), 15 (43%), and eight (23%) had grade 2, 3 to 4, and 5 ILD, respectively. On ILD recovery, 17 patients had EGFR TKI rechallenge with eight received osimertinib and nine received erlotinib. The risk of recurrent ILD was higher with osimertinib rechallenge than erlotinib (p = 0.0498). Of eight, five (63%) developed recurrent ILD on osimertinib rechallenge, including three patients with fatal outcomes. In contrast, only one of nine patients (11%) treated with erlotinib had recurrent ILD. Median time to second ILD occurrence was 4.7 (range 0.7-12) weeks. Median time-to-treatment failure of patients with erlotinib rechallenge was 13.2 months (95% confidence interval: 8.6-15.0). Conclusions: The risk of recurrent ILD was considerably higher with osimertinib rechallenge than erlotinib. Osimertinib rechallenge should be avoided, whereas erlotinib may be considered in patients with symptomatic osimertinib-induced ILD.

Metacognitive-Focused Occupational Therapy for Substance Abuse in Medical-Social Service Collaboration: a Case Report.

We describe a 26-year-old man who underwent Metacognitive-Focused Occupational Therapy for his substance abuse problems.

Can Quantitative Measures of T790M Allelic Fraction Predict Survival Outcomes in Patients Receiving Osimertinib? Observations From an Early Access Programme.

AIMS: Multiple studies have shown conflicting results on the correlation between the EGFR T790M quantitative level and survival outcomes in osimertinib-treated patients. We sought to validate such correlations using data from an osimertinib early access programme (EAP) providing access for metastatic non-small cell lung cancer patients with limited treatment options. PATIENTS AND METHODS: This observational, multicentre, retrospective analysis included EAP participants who received osimertinib until disease progression, intolerable toxicities or death. Digital droplet polymerase chain reaction-based quantitative plasma genotyping was carried out upon disease progression and data were analysed to explore the relationships between T790M mutant allele fraction (MAF), T790M copy number, MAF ratio and post-osimertinib overall survival. Real-world treatment outcomes and safety were also evaluated. RESULTS: Data from 156 EAP participants were analysed (median follow-up 37.7 months). The median age was 62 years, 62.2% were women, 79.5% were never-smokers, 60.9% had Eastern Cooperative Oncology Group performance status 0/1. In patients with available plasma data (n = 114), T790M MAF (%) showed no significant relationships with overall survival (hazard ratio 1.02; 95% confidence interval 0.99-1.04) or time to treatment discontinuation (TTD) (hazard ratio 1.01; 95% confidence interval 0.98-1.04). Absolute T790M copy number and T790M to activating EGFR mutation MAF ratio also showed no prognostic value. The investigator-assessed response rate was 42.3% and the disease control rate was 85.5%. The median TTD was 15.8 (95% confidence interval 12.5-18.5) months and the median overall survival was 22.3 (95% confidence interval 18.6-26.1) months. CONCLUSION: T790M MAF did not correlate with TTD or overall survival in this EAP cohort but limitations should not be overlooked. Observed survival outcomes and the toxicity profile were consistent with data from other real-world series.

Estimating sediment yield at Kaduna watershed, Nigeria using soil and water assessment tool (SWAT) model.

Over the years, sedimentation has posed a great danger to the storage capacity of hydropower reservoirs. Good understanding of the transport system and hydrological processes in the dam is very crucial to its sustainability. Under optimal functionality, the Shiroro dam in Northern Nigeria can generate ∼600 MW, which is ideally sufficient to power about 404,000 household. Unfortunately, there have not been reliable monitoring measures to assess yield in the upstream, where sediments are sourced into the dam. In this study, we applied the Soil and Water Assessment Tool (SWAT) to predict the hydrological processes, the sediment transport mechanism and sediment yield between 1990 and 2018 in Kaduna watershed (32,124 km2) located upstream of the dam. The model was calibrated and validated using observed flow and suspended sediment concentration (SSC) data. Performance evaluation of the model was achieved statistically using Nash-Sutcliffe (NS), coefficient of determination (r2) and percentage of observed data (p-factor). SWAT model evaluation using NS (0.71), r2 (0.80) and p-factors of 0.86 suggests that the model performed satisfactorily for streamflow and sediment yield predictions. The model identified the threshold depth of water (GWQMN.gw) and base flow (ALPHA_BF.gw) as the most sensitive parameters for streamflow and sediment yield estimation in the watershed. Our finding showed that an estimated suspended sediment yield of about 84.1 t/ha/yr was deposited within the period under study. Basins 67, 71 and 62 have erosion prone area with the highest sediment values of 79.4, 75.1 and 73.8 t/h respectively. Best management practice is highly recommended for the dam sustainability, because of the proximity of erosion-prone basins to the dam.

Pre-45s rRNA promotes colon cancer and is associated with poor survival of CRC patients.

One characteristic of cancer cells is the abnormally high rate of cell metabolism to sustain their enhanced proliferation. However, the behind mechanism of this phenomenon is still elusive. Here we find that enhanced precursor 45s ribosomal RNA (pre-45s rRNA) is one of the core mechanisms in promoting the pathogenesis of colorectal cancer (CRC). Pre-45s rRNA expression is significantly higher in primary CRC tumor tissues samples and cancer cell lines compared with the non-tumorous colon tissues, and is associated with tumor sizes. Knockdown of pre-45s rRNA inhibits G1/S cell-cycle transition by stabilizing p53 through inducing murine double minute 2 (MDM2) and ribosomal protein L11 (RpL11) interaction. In addition, we revealed that high rate of cancer cell metabolism triggers the passive release of calcium ion from endoplasmic reticulum to the cytoplasm. The elevated calcium ion in the cytoplasm activates the signaling cascade of calcium/calmodulin-dependent protein kinase II, ribosomal S6 kinase (S6K) and ribosomal S6K (CaMKII-S6K-UBF). The activated UBF promotes the transcription of rDNA, which therefore increases pre-45s rRNA. Disruption of CaMKII-S6K-UBF axis by either RNAi or pharmaceutical approaches leads to reduction of pre-45s rRNA expression, which subsequently suppresses cell proliferation in colon cancer cells by causing cell-cycle arrest. Knockdown of APC activates CaMKII-S6K-UBF cascade and thus enhances pre-45s rRNA expression. Moreover, the high expression level of pre-45s rRNA is associated with poor survival of CRC patients in two independent cohorts. Our study identifies a novel mechanism in CRC pathogenesis mediated by pre-45s rRNA and a prognostic factor of pre-45s rRNA in CRC patients.

Adjuvant S-1 chemotherapy after curative resection of gastric cancer in Chinese patients: assessment of treatment tolerability and associated risk factors.

INTRODUCTION: The use of adjuvant chemotherapy with S-1 (tegafur, gimeracil, and oteracil potassium) has been shown to improve the outcome of patients with gastric cancer. There are limited data on the tolerability of S-1 in Chinese patients. In this multicentre retrospective study, we assessed the toxicity profile in local patients. METHODS: Patients with stage II-IIIC gastric adenocarcinoma who had undergone curative resection and who had received S-1 adjuvant chemotherapy were included in the study. Patient demographics, tumour characteristics, chemotherapy records, as well as biochemical, haematological, and other toxicity profiles were extracted from medical charts. Potential factors associated with grade 2-4 toxicities were identified. RESULTS: Adjuvant S-1 was administered to 30 patients. Overall, 19 (63%) patients completed eight cycles. The most common grade 3-4 adverse events included neutropaenia (10%), anaemia (6.7%), septic episode (16.7%), diarrhoea (6.7%), hyperbilirubinaemia (6.7%), and syncope (6.7%). Dose reductions were made in 22 (73.3%) patients and 12 (40.0%) patients had dose delays. Univariate analyses showed that patients who underwent total gastrectomy were more likely to experience adverse haematological events (P=0.034). Patients with nodal involvement were more likely to report adverse non-haematological events (P=0.031). Patients with a history of regular alcohol intake were more likely to have earlier treatment withdrawal (P=0.044). Lower body weight (P=0.007) and lower body surface area (P=0.017) were associated with dose interruptions. CONCLUSIONS: The tolerability of adjuvant S-1 in our patient population was similar to that in other Asian patient populations. The awareness of S-1-related toxicities and increasing knowledge of potential associated factors may enable optimisation of S-1 therapy.

A randomised comparison of InnoScope and Macintosh laryngoscope in simulated difficult tracheal intubation in manikins.

We conducted a crossover randomised study to evaluate the performance of a novel optical stylet, the InnoScope, for tracheal intubation in simulated normal and difficult airways. Twenty-five anaesthetists attempted tracheal intubation on a SimMan 3G simulator using the InnoScope first followed by the Macintosh laryngoscope or vice versa. Three airway scenarios were tested: (1) normal airway; (2) difficult airway with swollen pharynx; and (3) limited neck movement. In each scenario, the laryngeal view, duration of and success rate for tracheal intubation were recorded. Compared with the Macintosh laryngoscope, the use of InnoScope increased the percentage of glottic opening seen by 17% in normal airway, 23% in the difficult airway and 32% with limited neck movement, p < 0.01. Despite this better laryngeal view, successful tracheal intubation achieved with the InnoScope (88.0%) was lower than that for the Macintosh laryngoscope (98.7%), p = 0.008. Using the InnoScope, tracheal intubation during the first attempt was only successful in 48% of cases with difficult airway. In this scenario, the median (interquartile range [range]) duration of tracheal intubation was significantly longer with [corrected] InnoScope compared with the Macintosh laryngoscope, (70 (19-120 [15-120)] s vs 30 [21-58 (15-120)] s, [corrected] p = 0.01. We conclude that an improved laryngeal view with the use of the InnoScope did not translate into better conditions for tracheal intubation.

Effectiveness of coordination exercise in improving cognitive function in older adults: a prospective study.

BACKGROUND: Studies on the effect of a low intensity coordination exercise on the elderly with limited mobility are sparse. This prospective study attempted to compare the effectiveness of a customized coordination exercise and a strength exercise in improving the cognitive functioning and physical mobility on the elderly. METHODS: Participants from two centers for the elderly were allocated to practice either an 8-week coordination training (CT) program or an 8-week towel exercise (TE) program. The Chinese Mini-Mental State Examination and Chinese Dementia Rating Scale (CDRS) were used to measure cognitive functioning of participants, and Timed Up-and-Go test for physical mobility. These assessments were administered before and after the program. RESULTS: Paired t-tests showed that the CDRS scores of the CT group improved significantly from 114.8 at pre-test to 119.3 after training (P = 0.045). The CDRS scores of the TE group also improved from 114.9 at pre-test to 116.9 after training. CONCLUSION: Findings from this prospective study demonstrated that low-intensity level mind-body exercise could be beneficial to the cognitive functioning of older adults.

A randomized study of aprepitant, ondansetron and dexamethasone for chemotherapy-induced nausea and vomiting in Chinese breast cancer patients receiving moderately emetogenic chemotherapy.

OBJECTIVES: This is a single center, randomized, double-blind placebo-controlled study to evaluate the NK(1)-receptor antagonist, aprepitant, in Chinese breast cancer patients. The primary objective was to compare the efficacy of aprepitant-based antiemetic regimen and standard antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients who received moderately emetogenic chemotherapy. The secondary objective was to compare the patient-reported quality of life in these two groups of patients. PATIENTS AND METHODS: Eligible breast cancer patients were chemotherapy-naive and treated with adjuvant AC chemotherapy (i.e. doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2)). Patients were randomly assigned to either an aprepitant-based regimen (day 1, aprepitant 125 mg, ondansetron 8 mg, and dexamethasone 12 mg before chemotherapy and ondansetron 8 mg 8 h later; days 2 through 3, aprepitant 80 qd) or a control arm which consisted of standard regimen (day 1, ondansetron 8 mg and dexamethasone 20 mg before chemotherapy and ondansetron 8 mg 8 h later; days 2 through 3, ondansetron 8 mg bid). Data on nausea, vomiting, and use of rescue medication were collected with a self-report diary, patients quality of life were assessed by self-administered Functional Living Index-Emesis (FLIE). RESULTS: Of 127 patients randomized, 124 were assessable. For CINV in Cycle 1 AC, there was no significant difference in the proportion of patients with reported complete response, complete protection, total control, 'no vomiting', 'no significant nausea' and 'no nausea'. The requirement of rescue medication appears to be lesser in patients treated with the aprepitant-based regimen compared to those with the standard regimen (11% vs. 20%; P = 0.06). Assessment of FLIE revealed that while there was no difference in the nausea domain and the total score between the two groups; however, patients receiving standard antiemetic regimen had significantly worse quality of life in the vomiting domain (mean score [SD] = 23.99 [30.79]) when compared with those who received the aprepitant-based regimen (mean score [SD] = 3.40 [13.18]) (P = 0.0002). Both treatments were generally well tolerated. Patients treated with the aprepitant-based regimen had a significantly lower incidence of neutropenia (53.2% vs. 35.5%, P = 0.0468), grade >or= 3 neutropenia (21.0% vs. 45.2, P = 0.0042) and delay in subsequent cycle of chemotherapy (8.1% vs. 27.4%, P = 0.0048). CONCLUSION: The aprepitant regimen appears to reduce the requirement of rescue medication when compared with the control regimen for prevention of CINV in patients receiving both an anthracycline and cyclophosphamide, and is associated with a better quality of life during adjuvant AC chemotherapy.

Guarding against natural disaster.

Natural disasters have caused death and damage in many places, with the health sector particularly vulnerable to such havoc. Hospitals have collapsed, or been so severely damaged that they have had to be evacuated. It appears that many of them have suffered a distinct lack of disaster mitigation planning during the design and construction phases. To ensure that healthcare facilities can continue to operate after a disaster has struck, at the very moment when they are needed most, the design methodology discussed in this article should be adopted. A successful outcome also demands strong collaboration from all participating construction professionals.

Adopting better paths to major schemes.

In recent decades, the construction industry has developed a range of procurement strategies to overcome perceived problems of inefficiency in the hospital building process.

Adjuvant chemoradiation for gastric cancer: experience in the Chinese population.

AIMS: The role of adjuvant chemoradiation for gastric cancer after curative R0 gastrectomy was first established by the US Intergroup 0116 study. Although confirmatory studies are in progress, few data are available regarding its application to the Chinese population. We describe our radiotherapy technique and report the treatment results in Hong Kong. MATERIALS AND METHODS: This was a single centre retrospective study on 63 Chinese patients who underwent adjuvant chemoradiation for gastric adenocarcinoma between June 2000 and December 2004. The treatment protocol was based on that of the Intergroup study. Computed tomography planned anteroposterior opposing field arrangement and treatment under breath hold at deep inspiration position were adopted. RESULTS: In total, 63 patients, mean age 50 years, with gastric cancer stage IB to limited metastatic IV disease were analysed. The median follow-up time was 27.2 months. The relapse-free survival and overall survival at 3 years were 50 and 54%, respectively. The recurrence pattern was dominated by distant failure and only one patient developed isolated locoregional recurrence. Of the 10 patients who had positive microscopic surgical margins after surgery, seven had recurred and died. On multivariate analysis, margin status was the only significant prognosticator for survival. Thirty per cent of patients experienced grade 3 or above acute toxicity (24% haematological, 14% gastrointestinal) and one patient died of neutropenic sepsis. There was one case of grade 3 late toxicity. CONCLUSIONS: The outcome after adjuvant chemoradiation for gastric cancer seemed to be favourable, with manageable toxicities, in the Chinese population. Locoregional failure was uncommon. Patients with microscopic surgical margin involvement had a very high failure rate despite adjuvant chemoradiation.

Essential tasks must be programmed effectively.

Few would argue that maintenance is not a problem. Practices do not eliminate problems, but only proper practice makes perfect maintenance. To master management of building services maintenance, there is no better teacher than experience. You must plan your maintenance system thoughtfully and try it out together with your professional knowledge. The system outlined in this article gives a systematic procedure in setting up a workable maintenance plan. The tedious management work and the inconvenience caused to a busy or new maintenance department will probably mean greater pressure of work for the maintenance engineer in the first year, but thereafter the pressure will be less than before and benefits of an organised system of maintenance will repay the effort of introducing it. It is essential that the paperwork be as simple as possible and very flexible in operation so that amendments can be made easily. Preparation of paperwork is by no means easy. It is highly likely that your schedules and programmes will have to be rewritten two or three times before arriving at the optimum plan. My management lecturer once told me: "Without a plan and a programme, you don't know whether you have done all the things that you need to do, and you will end up with many problems." Good planning gives you confidence, but take my advice--do not over plan. Too much paperwork can be just as bad if not worse than too little paper. Information will be of no use if it cannot be read, digested and used in practice.

A double-blind placebo-controlled randomized study of Chinese herbal medicine as complementary therapy for reduction of chemotherapy-induced toxicity.

BACKGROUND: Chinese herbal medicine (CHM) is a common complementary therapy used by patients with cancer for reduction of chemotherapy-induced toxic effects. This study applied the highest standard of clinical trial methodology to examine the role of CHM in reducing chemotherapy-induced toxicity, while maintaining a tailored approach to therapy. PATIENTS AND METHODS: Patients with early-stage breast or colon cancer who required postoperative adjuvant chemotherapy were eligible for the study. Enrolled patients were randomly assigned to one of three Chinese herbalists who evaluated and prescribed a combination of single-item packaged herbal extract granules. Patients received either CHM or placebo packages with a corresponding serial number. The placebo package contained nontherapeutic herbs with an artificial smell and taste similar to a typical herbal tea. The primary end points were hematologic and non-hematologic toxicity according to the National Cancer Institute Common Toxicity Criteria Version 2. RESULTS: One hundred and twenty patients were accrued at the time of premature study termination. Patient characteristics of the two groups were similar. The incidence of grade 3/4 anemia, leukopenia, neutropenia, and thrombocytopenia for the CHM and placebo groups were 5.4%, 47.3%, 52.7%, and 1.8% and 1.8%, 32.2%, 44.7%, and 3.6%, respectively (P = 0.27, 0.37, 0.63, and 0.13, respectively). Incidence of grade 2 nausea was the only non-hematologic toxicity that was significantly reduced in the CHM group (14.6% versus 35.7%, P = 0.04). CONCLUSIONS: Traditional CHM does not reduce the hematologic toxicity associated with chemotherapy. CHM, however, does have a significant impact on control of nausea.