Functional outcome after selective dorsal rhizotomy: a retrospective case control study.

PURPOSE: This study examines long-term benefit on functional outcomes and quality of life after selective dorsal rhizotomy (SDR) in children with spastic diplegia in Hong Kong. METHOD: This is a case control study. Individuals with spastic diplegia who were at 6 to 12 years post-SDR were recruited. Age, gender, cognition, and Gross Motor Function Classification System level-matched individuals with spastic diplegia who had not undergone SDR were recruited as controls. Outcome measures included physical level, functional level, physiological level, and quality of life. All data were compared by independent t-test. RESULTS: Individuals post-SDR (n = 15) demonstrated a significantly better range of ankle dorsiflexion in knee extension by - 5.7 ± 10.9° than the control group (n = 12). No other significant differences were observed. CONCLUSION: SDR is a safe, one-off procedure and provides long-term reduction in spasticity with no major complications. With the heterogeneity, we did not demonstrate between-group differences in long-term functional outcomes.

Translation and validation of Cerebral Palsy Quality of Life Questionnaire-Teen in Hong Kong Chinese population [CP QoL-Teen (HK)].

Cerebral palsy (CP) is an early onset, non-progressive, neuromotor disorder. Adolescence is the transition from childhood to adulthood when changes in physical and emotional aspects and self-perception occur further imposing an impact to quality of life (QoL) in individuals with CP. Cerebral Palsy Quality of Life (CP QoL) Teen is a questionnaire examining different domains of QoL for adolescents with CP. This study is aimed at translating and validating self-report and proxy-report CP QoL-Teen (HK). Prior approval of translation has been obtained. Forward and backward translations were performed following standardized translation procedures. Participants and their caregivers were asked to complete self-report and proxy-report CP QoL-Teen (HK), and Child Health Questionnaire (CHQ). Internal consistency and test-retest reliability were assessed by Cronbach's alpha and intraclass correlation coefficient (ICC), respectively. Concurrent validity was evaluated by Spearman's rank correlation between subscales of CP QoL-Teen (HK) and CHQ as well as expanded and revised version of Gross Motor Function Classification System (GMFCS-E&R). Ninety-six participants completed the study. Of these, twenty participants completed CP QoL-Teen (HK) twice. Cronbach's α of CP QoL-Teen (HK) ranged from 0.84 to 0.95 suggesting excellent internal consistency. Moderate to excellent test-retest reliability were demonstrated in all subscales of CP QoL-Teen (HK) (self-report: ICC = 0.46-0.8; proxy-report: ICC = 0.40-0.72, p < 0.05). Weak to moderate association between subscales of CP QoL-Teen (HK) and CHQ (self-report: rs = 0.24-0.61; proxy-report: rs = - 0.41-0.60) was reported. CONCLUSION: This study showed that CP QoL-Teen (HK) has good psychometric properties. It is a valid and reliable tool to assess quality of life of adolescents with CP. WHAT IS KNOWN: • Cerebral Palsy Quality of life-Teen (CP QoL-Teen) is a validated tool with strong psychometric properties and clinical utility in gauging the QoL in adolescents with CP during their transition from childhood to adulthood when changes in physical and emotional aspects and self-perception occur. Yet, a locally validated tool is lacking in measuring the QoL for adolescents with CP in Hong Kong. WHAT IS NEW: • The Chinese translated version CP QoL-Teen (HK) is a valid and reliable tool to assess quality of life of adolescents with CP tailoring to the local cultural and social background with good psychometric properties being demonstrated.

Machine learning to predict myocardial injury and death after non-cardiac surgery.

Myocardial injury due to ischaemia within 30 days of non-cardiac surgery is prognostically relevant. We aimed to determine the discrimination, calibration, accuracy, sensitivity and specificity of single-layer and multiple-layer neural networks for myocardial injury and death within 30 postoperative days. We analysed data from 24,589 participants in the Vascular Events in Non-cardiac Surgery Patients Cohort Evaluation study. Validation was performed on a randomly selected subset of the study population. Discrimination for myocardial injury by single-layer vs. multiple-layer models generated areas (95%CI) under the receiver operating characteristic curve of: 0.70 (0.69-0.72) vs. 0.71 (0.70-0.73) with variables available before surgical referral, p < 0.001; 0.73 (0.72-0.75) vs. 0.75 (0.74-0.76) with additional variables available on admission, but before surgery, p < 0.001; and 0.76 (0.75-0.77) vs. 0.77 (0.76-0.78) with the addition of subsequent variables, p < 0.001. Discrimination for death by single-layer vs. multiple-layer models generated areas (95%CI) under the receiver operating characteristic curve of: 0.71 (0.66-0.76) vs. 0.74 (0.71-0.77) with variables available before surgical referral, p = 0.04; 0.78 (0.73-0.82) vs. 0.83 (0.79-0.86) with additional variables available on admission but before surgery, p = 0.01; and 0.87 (0.83-0.89) vs. 0.87 (0.85-0.90) with the addition of subsequent variables, p = 0.52. The accuracy of the multiple-layer model for myocardial injury and death with all variables was 70% and 89%, respectively.

Rubella vaccine-induced granulomas are a novel phenotype with incomplete penetrance of genetic defects in cytotoxicity.

BACKGROUND: Rubella virus-induced granulomas have been described in patients with various inborn errors of immunity. Most defects impair T-cell immunity, suggesting a critical role of T cells in rubella elimination. However, the molecular mechanism of virus control remains elusive. OBJECTIVE: This study sought to understand the defective effector mechanism allowing rubella vaccine virus persistence in granulomas. METHODS: Starting from an index case with Griscelli syndrome type 2 and rubella skin granulomas, this study combined an international survey with a literature search to identify patients with cytotoxicity defects and granuloma. The investigators performed rubella virus immunohistochemistry and PCR and T-cell migration assays. RESULTS: This study identified 21 patients with various genetically confirmed cytotoxicity defects, who presented with skin and visceral granulomas. Rubella virus was demonstrated in all 12 accessible biopsies. Granuloma onset was typically before 2 years of age and lesions persisted from months to years. Granulomas were particularly frequent in MUNC13-4 and RAB27A deficiency, where 50% of patients at risk were affected. Although these proteins have also been implicated in lymphocyte migration, 3-dimensional migration assays revealed no evidence of impaired migration of patient T cells. Notably, patients showed no evidence of reduced control of concomitantly given measles, mumps, or varicella live-attenuated vaccine or severe infections with other viruses. CONCLUSIONS: This study identified lymphocyte cytotoxicity as a key effector mechanism for control of rubella vaccine virus, without evidence for its need in control of live measles, mumps, or varicella vaccines. Rubella vaccine-induced granulomas are a novel phenotype with incomplete penetrance of genetic disorders of cytotoxicity.

Knowledge, attitudes, and behaviours of pregnant women towards COVID-19: a cross-sectional survey.

INTRODUCTION: This study investigated the knowledge, attitudes, and behaviours of pregnant women towards coronavirus disease 2019 (COVID-19), as well as obstetric services provided by public hospitals (eg, universal screening) during the pandemic. METHODS: This cross-sectional survey was performed in the antenatal clinics of Kowloon East Cluster, Hospital Authority. Questionnaires were distributed to pregnant women for self-completion during follow-up examinations. RESULTS: In total, 623 completed questionnaires were collected from 28 July 2020 to 13 August 2020. Within this cohort, 83.1% of the women expressed high levels of worry (41.9% very worried and 41.3% worried) about contracting COVID-19 during pregnancy, 70.5% believed that maternal COVID-19 could cause intrauterine infection of their fetuses, and 84.3% objected to banning husbands from accompanying wives during labour and delivery. Most women (80.6%) agreed with universal screening for COVID-19 at certain points during pregnancy. Logistic regression modelling showed that women who were very worried about contracting COVID-19 (P=0.005) and women in their third trimester of pregnancy (P=0.009) were more likely to agree with universal screening during pregnancy; women with higher income (P=0.017) and women who planned to deliver in a private hospital (P=0.024) were more likely to disagree with such screening. CONCLUSION: Pregnant women expressed high levels of worry about contracting COVID-19 during pregnancy; universal screening during pregnancy was acceptable to a large proportion of our participants. Efforts should be made to specifically include pregnant women when launching any population screening programme for COVID-19.

A discussion on implementing pooling detection tests of novel coronavirus (SARS-CoV-2) for a large population.

A pooled sample analysis strategy for novel coronavirus (severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)) is proposed for a large population in this paper. The population to be tested is divided into divisions based on earlier observed detection rate of SARS-CoV-2 first. Samples collected are then grouped in appropriate pooled size. The number of tests per person in that population is expressed as a function of two variables: the observed detection rate and the pooled size or number of samples grouped. The minimum number of tests per person can be further shown to be a function of only one of these two variables, because these two parameters are found to be related at this minimum. A management scheme on grouping the samples is proposed in order to reduce the number of tests, to save time, which is of utmost importance in fighting an epidemic. The proposed testing scheme will be useful for supporting the government in making decisions to handle regular routine detection tests for identifying asymptomatic patients and implementing health code system in large population of millions of citizens. Another important point is to use smaller number of test kits, allowing more resources to speed up the mass screening tests, particularly in places not so rich.

A discussion on the minimum required number of tests in two common pooling test methods for SARS-CoV-2.

Pooling of samples in detecting the presence of virus is an effective and efficient strategy in screening carriers in a large population with low infection rate, leading to reduction in cost and time. There are a number of pooling test methods, some being simple and others being complicated. In such pooling tests, the most important parameter to decide is the pool or group size, which can be optimised mathematically. Two pooling methods are relatively simple. The minimum numbers required in these two tests for a population with known infection rate are discussed and compared. Results are useful for identifying asymptomatic carriers in a short time and in implementing health codes systems.

Structural determination of arginine-linked cisplatin complexes via IRMPD action spectroscopy: arginine binds to platinum via NO- binding mode.

Cisplatin, (NH3)2PtCl2, has been known as a successful metal-based anticancer drug for more than half a century. Its analogue, Argplatin, arginine-linked cisplatin, (Arg)PtCl2, is being investigated because it exhibits reactivity towards DNA and RNA that differs from that of cisplatin. In order to understand the basis for its altered reactivity, the deprotonated and sodium cationized forms of Argplatin, [(Arg-H)PtCl2]- and [(Arg)PtCl2 + Na]+, are examined by infrared multiple photon dissociation (IRMPD) action spectroscopy in the IR fingerprint and hydrogen-stretching regions. Complementary electronic structure calculations are performed using density functional theory approaches to characterize the stable structures of these complexes and to predict their infrared spectra. Comparison of the theoretical IR spectra predicted for various stable conformations of these Argplatin complexes to their measured IRMPD spectra enables determination of the binding mode(s) of Arg to the Pt metal center to be identified. Arginine is found to bind to Pt in a bidentate fashion to the backbone amino nitrogen and carboxylate oxygen atoms in both the [(Arg-H)PtCl2]- and [(Arg)PtCl2 + Na]+ complexes, the NO- binding mode. The neutral side chain of Arg also interacts with the Pt center to achieve additional stabilization in the [(Arg-H)PtCl2]- complex. In contrast, Na+ binds to both chlorido ligands in the [(Arg)PtCl2 + Na]+ complex and the protonated side chain of Arg is stabilized via hydrogen-bonding interactions with the carboxylate moiety. These findings are consistent with condensed-phase results, indicating that the NO- binding mode of arginine to Pt is preserved in the electrospray ionization process even under variable pH and ionic strength.

Trajectories of Alcohol Use and Related Harms for Managed Alcohol Program Participants over 12 Months Compared with Local Controls: A Quasi-Experimental Study.

AIM: Investigate changes in alcohol use and related harm using the first multisite, controlled, longitudinal study of Managed Alcohol Programs (MAPs). MAPs provide regular doses of alcohol, accommodation, social supports and healthcare to unstably housed people with alcohol dependence. METHODS: A multisite, quasi-experimental, longitudinal study was conducted in day centres, shelters and residential programs for unstably housed people. There were 59 MAP participants from six Canadian cities and 116 local controls. Self-reported alcohol consumption and harms were assessed at 0-2, 6 and 12 months. Liver function test results were accessed for MAP participants. RESULTS: Both groups had similar reductions in mean drinks per day (MAP: -8.11; controls: -8.54 controls, P < 0.001) and days drinking per month (MAP: -2.51 days, P < 0.05; control: -4.81 days, P = 0.0001) over 6--12 months. Both reduced non-beverage alcohol consumption. MAP participants reported significantly fewer harms at both 0-2 and 6 months than controls. MAP participants had similar total consumption to controls, but spread out over more days (25.41 versus 19.64 days per month, P = 0.001). After leaving a MAP, participants' liver status deteriorated, with increases in both aspartate transaminase and bilirubin levels. MAP sites with effective policies on outside drinking drank less and had fewer harms. CONCLUSION: MAP participants drank less hazardously than controls, especially with effective management of non-MAP drinking. Reductions in alcohol use and harms occurred for both groups, although MAP participants reported fewer harms at 0-6 months. Departing an MAP was associated with deterioration in liver status. Although providing stable housing, MAPs did not worsen health or increase alcohol use.

Hydrocele in a case of atypical Kawasaki disease: case report and review of diagnostic criteria.

BACKGROUND: Kawasaki Disease (KD) is a self-limiting vasculitis of unknown etiology. Although there are well-recognized clinical features associated with classic KD, there have been increasing numbers of atypical clinical presentations with increased dependence on the American Heart Association diagnostic algorithm for incomplete KD. CASE PRESENTATION: We report on a child who was initially treated for Escherichia coli left pyelonephritis and Influenza A and Rhinovirus / Enterovirus upper respiratory tract infection. The child developed an acute hydrocele and a maculopapular rash during the illness course, which prompted further evaluation for concomitant atypical KD, although there were no other physical signs suggestive of classic KD at the time. Subsequent diagnosis of atypical KD was made with confirmation on echocardiography, with timely administration of intravenous immunoglobulin. CONCLUSIONS: Although there are well recognized clinical features associated with classic Kawasaki Disease, there have been increasing numbers of atypical clinical presentations with increased dependence on the American Heart Association diagnostic algorithm for incomplete Kawasaki Disease. This case report highlights the importance of considering a diagnosis of KD in a child with prolonged fever and unexplainable symptoms suggestive of inflammation, in this case, the rare presentation of an acute hydrocele. We recommend that for any child with prolonged unexplained fever, Kawasaki Disease should be considered. TRIAL REGISTRATION: Not applicable.

A data-driven model for COVID-19 pandemic - Evolution of the attack rate and prognosis for Brazil.

We introduce a compartmental model SEIAHRV (Susceptible, Exposed, Infected, Asymptomatic, Hospitalized, Recovered, Vaccinated) with age structure for the spread of the SARAS-CoV virus. In order to model current different vaccines we use compartments for individuals vaccinated with one and two doses without vaccine failure and a compartment for vaccinated individual with vaccine failure. The model allows to consider any number of different vaccines with different efficacies and delays between doses. Contacts among age groups are modeled by a contact matrix and the contagion matrix is obtained from a probability of contagion p c per contact. The model uses known epidemiological parameters and the time dependent probability p c is obtained by fitting the model output to the series of deaths in each locality, and reflects non-pharmaceutical interventions. As a benchmark the output of the model is compared to two good quality serological surveys, and applied to study the evolution of the COVID-19 pandemic in the main Brazilian cities with a total population of more than one million. We also discuss with some detail the case of the city of Manaus which raised special attention due to a previous report of We also estimate the attack rate, the total proportion of cases (symptomatic and asymptomatic) with respect to the total population, for all Brazilian states since the beginning of the COVID-19 pandemic. We argue that the model present here is relevant to assessing present policies not only in Brazil but also in any place where good serological surveys are not available.

DAMAC: A Delay-Aware MAC Protocol for Ad Hoc Underwater Acoustic Sensor Networks.

In a channel shared by several nodes, the scheduling algorithm is a key factor to avoiding collisions in the random access-based approach. Commonly, scheduling algorithms can be used to enhance network performance to meet certain requirements. Therefore, in this paper we propose a Delay-Aware Media Access Control (DAMAC) protocol for monitoring time-sensitive applications over multi-hop in Underwater Acoustic Sensor Networks (UASNs), which relies on the random access-based approach where each node uses Carrier Sense Multiple Access/Collision Avoidance (CSMA/CA) to determine channel status, switches nodes on and off to conserve energy, and allows concurrent transmissions to improve the underwater communication in the UASNs. In addition, DAMAC does not require any handshaking packets prior to data transmission, which helps to improve network performance in several metrics. The proposed protocol considers the long propagation delay to allow concurrent transmissions, meaning nodes are scheduled to transmit their data packets concurrently to exploit the long propagation delay between underwater nodes. The simulation results show that DAMAC protocol outperforms Aloha, BroadcastMAC, RMAC, Tu-MAC, and OPMAC protocols under varying network loads in terms of energy efficiency, communication overhead, and fairness of the network by up to 65%, 45%, and 726%, respectively.

Association of technologically assisted integrated care with clinical outcomes in type 2 diabetes in Hong Kong using the prospective JADE Program: A retrospective cohort analysis.

BACKGROUND: Diabetes outcomes are influenced by host factors, settings, and care processes. We examined the association of data-driven integrated care assisted by information and communications technology (ICT) with clinical outcomes in type 2 diabetes in public and private healthcare settings. METHODS AND FINDINGS: The web-based Joint Asia Diabetes Evaluation (JADE) platform provides a protocol to guide data collection for issuing a personalized JADE report including risk categories (1-4, low-high), 5-year probabilities of cardiovascular-renal events, and trends and targets of 4 risk factors with tailored decision support. The JADE program is a prospective cohort study implemented in a naturalistic environment where patients underwent nurse-led structured evaluation (blood/urine/eye/feet) in public and private outpatient clinics and diabetes centers in Hong Kong. We retrospectively analyzed the data of 16,624 Han Chinese patients with type 2 diabetes who were enrolled in 2007-2015. In the public setting, the non-JADE group (n = 3,587) underwent structured evaluation for risk factors and complications only, while the JADE (n = 9,601) group received a JADE report with group empowerment by nurses. In a community-based, nurse-led, university-affiliated diabetes center (UDC), the JADE-Personalized (JADE-P) group (n = 3,436) received a JADE report, personalized empowerment, and annual telephone reminder for reevaluation and engagement. The primary composite outcome was time to the first occurrence of cardiovascular-renal diseases, all-site cancer, and/or death, based on hospitalization data censored on 30 June 2017. During 94,311 person-years of follow-up in 2007-2017, 7,779 primary events occurred. Compared with the JADE group (136.22 cases per 1,000 patient-years [95% CI 132.35-140.18]), the non-JADE group had higher (145.32 [95% CI 138.68-152.20]; P = 0.020) while the JADE-P group had lower event rates (70.94 [95% CI 67.12-74.91]; P < 0.001). The adjusted hazard ratios (aHRs) for the primary composite outcome were 1.22 (95% CI 1.15-1.30) and 0.70 (95% CI 0.66-0.75), respectively, independent of risk profiles, education levels, drug usage, self-care, and comorbidities at baseline. We reported consistent results in propensity-score-matched analyses and after accounting for loss to follow-up. Potential limitations include its nonrandomized design that precludes causal inference, residual confounding, and participation bias. CONCLUSIONS: ICT-assisted integrated care was associated with a reduction in clinical events, including death in type 2 diabetes in public and private healthcare settings.

Age, sex, and disease status as determinants of skin hydration and transepidermal water loss among children with and without eczema.

PURPOSE: Skin hydration (SH) and transepidermal water loss (TEWL) are important skin biophysical parameters for assessment of childhood eczema. This study investigated whether age, sex, and disease status influence these parameters. METHODS: Skin hydration and TEWL were measured by Delfin MoistureMeterSC and Delfin Vapometer SWL5, respectively, among children aged ≤18 years with and without eczema. Disease status was evaluated using Scoring Atopic Dermatitis (SCORAD) and Nottingham Eczema Severity Score (NESS) clinical tools. RESULTS: Clinical scores and objective measurements were reviewed for 132 patients with eczema and 120 patients without eczema. In both sexes, SH was significantly higher among children aged ≤2 years with and without eczema than among children aged >2 years with and without eczema. Among children aged >2 years, SH was higher among girls with and without eczema than among boys with and without eczema. Regardless of age or sex, SH was lower among children with eczema than among children without eczema. Age-, sex-, and disease-related differences were not observed for TEWL. Skin hydration was negatively correlated with objective SCORAD (r=-0.418, P<0.001), overall SCORAD (r=-0.385, P<0.001), oedema/papulation (r=-0.243, P=0.041), lichenification (r=-0.363, P=0.002), dryness (r=-0.415, P<0.001), and intensity (r=-0.266, P=0.025). Transepidermal water loss was positively correlated with objective SCORAD (r=0.209, P=0.018), overall SCORAD (r=0.215, P=0.015), and lichenification (r=0.240, P=0.043). Skin hydration was negatively correlated with TEWL among children without eczema (r=-0.401, P<0.001), but not among children with eczema. CONCLUSION: Skin hydration can be used to distinguish clinical differences in eczema based on age, sex, and disease status.

Trajectories of large respiratory droplets in indoor environment: A simplified approach.

The recent pandemic of COVID-19 has brought about tremendous impact on every aspect of human activities all over the world. The main route of transmission is believed to be through coronavirus-bearing respiratory droplets. The respiratory droplets have a wide spectrum in droplet size, ranging from very small droplets (aerosol droplets) to large droplets of tens and even hundreds of µm in size. The large droplets are expected to move like projectiles under the action of gravity force, buoyancy force and air resistance. Droplet motion is complicated by droplet evaporation, which reduces droplet size in its trajectory and affects the force acting on it. The present work attempts to determine the trajectories of the large droplets by using a simplified single-droplet approach. It aims at providing a clear physical picture to elucidate the mechanics involved in single droplet motion and the various factors affecting the range. Assuming an indoor environment with an air temperature of 18 °C and relative humidity of 50%, the horizontal range L x of large respiratory droplets (diameter 120 µm-200 µm) in common respiratory activities are as follows: Speaking, L x ≈ 0.16 m-0.68 m, coughing, L x ≈ 0.58 m-1.09 m, and sneezing, L x ≈ 1.34 m-2.76 m. For the smaller droplets (diameter < 100 µm), the droplets are reduced to aerosol droplets (≤5 µm) due to evaporation, and will remain suspended in the air instead of falling onto the ground like a projectile.

Collagenofibrotic glomerulopathy- report of a rare renal disease with serial biopsies.

INTRODUCTION: Collagenofibrotic glomerulopathy or collagen type-III glomerulopathy is a rare glomerular disease characterised by the deposition of type III collagen fibres in the subendothelial space and mesangium of the glomerulus. CASE REPORT: Here, we present a case of collagenofibrotic glomerulopathy in a 49-year-old Indian female, the first to be reported from Singapore. Renal biopsy showed PAS (periodic acid-Schiff), silver and Congo red negative, amorphous extracellular material that expanded mesangial and subendothelial regions. Such materials were strongly positive for anti-collagen III immunofluorescent staining. Under electron microscopy, the mesangial and some subendothelial regions were greatly expanded by abundant collagen fibres which were different from normal collagen III fibres in both appearance and periodicity. DISCUSSION: The availability of past renal biopsies for reference offered insight into disease progression. From the initial diagnosis of focal segmental glomerulosclerosis to eventually collagenofibrotic glomerulopathy over a time span of more than 10 years, this case highlights the gradual accumulation of collagen fibres in the glomeruli before classical features are apparent. It also emphasises the importance of electron microscopy in the diagnosis of this disease.

A text message intervention to support women's physical and mental health after breast cancer treatments (EMPOWER-SMS): a randomised controlled trial protocol.

BACKGROUND: Breast cancer is the most common cancer diagnosed in women worldwide. In developed countries, 80-90% of women will survive five years after diagnosis but the transition from hospital-based care to health self-management and self-efficacy can be difficult. Text messaging programs offer a simple and proven way to provide support to people with chronic diseases. This study aims to test the effectiveness of a text message support program at improving women's health self-efficacy, and physical and mental health outcomes after breast cancer treatments compared to usual care at 6-months and to understand the barriers and enablers to widespread implementation. METHODS: Single-blind randomised control trial (RCT; N = 160) comparing a text message support intervention to usual care in women with breast cancer (recruited from a large tertiary referral hospital in Sydney, Australia). The intervention group will receive a six-month text message support program, which consists of semi-personalised, supportive, lifestyle-focused text messages (4 messages/week) in addition to usual care. The control group will receive usual care without the text message program. Outcomes will be assessed at 6-months. The primary outcome is change in self-efficacy for managing chronic disease. Secondary outcomes include change in clinical outcomes (body mass index), lifestyle outcomes (physical activity levels, dietary behaviours), mood (depression and anxiety scales), quality of life, satisfaction with, and usefulness of the intervention. Analyses will be performed on the principle of intention-to-treat to examine differences between intervention and control groups. DISCUSSION: This study will test if a scalable and cost-effective text-messaging intervention is effective at improving women's health self-efficacy, as well as physical and mental health outcomes. Moreover, this study will provide essential preliminary data to bolster a large multicentre RCT to helpsupport breast cancer survivors throughout recovery and beyond. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry (ANZCTR) number ACTRN12618002020268 , 17 December 2018.

Whole-exome sequencing and immune profiling of early-stage lung adenocarcinoma with fully annotated clinical follow-up.

Background: Lung adenocarcinomas (LUADs) lead to the majority of deaths attributable to lung cancer. We performed whole-exome sequencing (WES) and immune profiling analyses of a unique set of clinically annotated early-stage LUADs to better understand the pathogenesis of this disease and identify clinically relevant molecular markers. Methods: We performed WES of 108 paired stage I-III LUADs and normal lung tissues using the Illumina HiSeq 2000 platform. Ten immune markers (PD-L1, PD-1, CD3, CD4, CD8, CD45ro, CD57, CD68, FOXP3 and Granzyme B) were profiled by imaging-based immunohistochemistry (IHC) in a subset of LUADs (n = 92). Associations among mutations, immune markers and clinicopathological variables were analyzed using ANOVA and Fisher's exact test. Cox proportional hazards regression models were used for multivariate analysis of clinical outcome. Results: LUADs in this cohort exhibited an average of 243 coding mutations. We identified 28 genes with significant enrichment for mutation. SETD2-mutated LUADs exhibited relatively poor recurrence- free survival (RFS) and mutations in STK11 and ATM were associated with poor RFS among KRAS-mutant tumors. EGFR, KEAP1 and PIK3CA mutations were predictive of poor response to adjuvant therapy. Immune marker analysis revealed that LUADs in smokers and with relatively high mutation burdens exhibited increased levels of immune markers. Analysis of immunophenotypes revealed that LUADs with STK11 mutations exhibited relatively low levels of infiltrating CD4+/CD8+ T-cells indicative of a muted immune response. Tumoral PD-L1 was significantly elevated in TP53 mutant LUADs whereas PIK3CA mutant LUADs exhibited markedly down-regulated PD-L1 expression. LUADs with TP53 or KEAP1 mutations displayed relatively increased CD57 and Granzyme B levels indicative of augmented natural killer (NK) cell infiltration. Conclusion(s): Our study highlights molecular and immune phenotypes that warrant further analysis for their roles in clinical outcomes and personalized immune-based therapy of LUAD.