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Video Video 1 Remote training in flexible GI endoscopy.

Background Adjuvant endocrine therapies are known to induce undesirable adverse effects such as vasomotor, vaginal and musculoskeletal symptoms among breast cancer patients. Drugs used in these therapies are often metabolised by cytochrome P450 (CYP) enzymes, in which their metabolising activities can be modified by single nucleotide polymorphisms (SNP) in CYP genes and CYP genotypes. This review aims to explore whether SNPs or genotypes of CYP are associated with the occurrence, frequency and severity of vasomotor, vaginal and musculoskeletal symptoms in breast cancer patients on adjuvant endocrine therapies. Methods A literature review was conducted using five electronic databases, resulting in the inclusion of 14 eligible studies, and their findings were presented narratively. Selected items from the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist were used for critical appraisal of the reporting quality of the included studies. Results Most of the included studies showed that SNPs or genotypes of CYP that modify its metabolising activity have no effect on the occurrence, frequency or severity of vasomotor symptoms, including hot flashes. One study showed no correlation of these genetic variations in CYP with musculoskeletal symptoms, and no data were available on the association between such genetic variations and vaginal symptoms. Conclusions Overall, genetic variations in CYP have no effect on the experience of hot flashes among breast cancer patients. We recommend exploration of the link between the active metabolites of chemotherapeutic drugs and the molecules shown to affect the occurrence or severity of hot flashes, and the establishment of the relationship between such genetic variations and patients’ experience of musculoskeletal and vaginal symptoms. Subgroup analyses based on patients’ duration of adjuvant endocrine therapies in such studies are recommended.

Background: Antidepressant drugs in adolescent depression are sometimes mired by efficacy issues and paradoxical effects. Transcranial direct current stimulation (tDCS) could represent an alternative. Aims/methods: We tested the antidepressant action of prefrontal tDCS and paroxetine (20 mg/kg, intraperitoneal) in olfactory bulbectomised (OBX) adolescent rats. Using enzyme-linked immunosorbent assays and in situ hybridisation, we examined treatment-induced changes in plasma brain-derived neurotrophic factor (BDNF) and brain serotonin transporter (SERT) and 5-HT-1A mRNA. Results: OBX-induced anhedonia-like reductions in sucrose preference (SP) correlated with open field (OF) hyperactivity. These were accompanied by decreased zif268 mRNA in the piriform/amygdalopiriform transition area, and increased zif268 mRNA in the hypothalamus. Acute paroxetine (2 days) led to a profound SP reduction, an effect blocked by combined tDCS–paroxetine administration. Chronic (14 days) tDCS attenuated hyperlocomotion and its combination with paroxetine blocked OBX-induced SP reduction. Correlations among BDNF, SP and hyperlocomotion scores were altered by OBX but were normalised by tDCS–paroxetine co-treatment. In the brain, paroxetine increased zif268 mRNA in the hippocampal CA1 subregion and decreased it in the claustrum. This effect was blocked by tDCS co-administration, which also increased zif268 in CA2. tDCS-paroxetine co-treatment had variable effects on 5-HT1A receptors and SERT mRNA. 5-HT1A receptor changes were found exclusively within depression-related parahippocampal/hippocampal subregions, and SERT changes within fear/defensive response-modulating brainstem circuits. Conclusion: These findings point towards potential synergistic efficacies of tDCS and paroxetine in the OBX model of adolescent depression via mechanisms associated with altered expression of BDNF, 5-HT1A, SERT and zif268 in discrete corticolimbic areas.

ObjectivesWith improved access to intrauterine transfusion (IUT), more fetuses with haemoglobin Bart’s hydrops fetalis (HBHF; homozygous α0-thalassaemia) will survive.DesignTo evaluate the long-term outcome of affected fetuses with and without IUT in Ontario, Canada, we retrospectively collected data on IUTs and pregnancy outcomes in all cases of HBHF, from 1989 to 2014. Clinical outcome and neurocognitive profiles of long-term survivors were also collected and compared with data from 24 patients with transfusion-dependent β-thalassaemia (TDT-β).ResultsOf the 99 affected pregnancies (93 prenatally diagnosed), 68 resulted in miscarriage or elective termination of pregnancy. Twelve mothers (12%) continued their pregnancies without IUT, and none of those newborns survived the first week of life. All 13 fetuses that received IUT(s) were live-born, but 3 died due to severe hydrops at birth and 1 died due to infection. The remaining nine survivors, in comparison with TDT-β patients, had earlier iron overload requiring iron chelation therapy. Endocrinopathies and short stature were more frequent in these patients. Neurocognitive outcome was not significantly affected in five patients who were assessed, and none were diagnosed with intellectual impairment. In three patients, MRI studies demonstrated brain white matter changes in keeping with ‘silent’ ischaemic infarcts.ConclusionsIn patients with HBHF, IUT is associated with improved survival. While acceptable neurocognitive outcome can be expected, these patients have more clinical complications compared with their TDT-β counterparts. The clinical and neurocognitive outcomes of HBHF should be discussed in detail when counselling and offering IUT for patients.

To review recent pharmacogenomics studies on breast cancer patients undergoing tamoxifen therapy, highlighting how our knowledge on cytochrome P450 2D6 (CYP2D6) can help to guide the development of adjuvant therapies for these patients. A comprehensive literature search was conducted. Articles reporting findings pertaining to the effect of CYP2D6 on the therapeutic efficacy of tamoxifen, those reporting how targeting CYP2D6 could inform tamoxifen-based therapy development, and those on the tamoxifen effects on cell lines and animal models were included in the review. With CYP2D6 being the primary enzyme for tamoxifen metabolism, single-nucleotide polymorphisms (SNPs) in this gene were one of the determinants in the rate of tamoxifen metabolism, thereby potentially having an effect on the efficacy of tamoxifen-based therapies. Our review indicates the potential effectiveness of targeting these SNPs, including those for the CYP2D6*10 allele (c. 100C > T), in modifying the level of tamoxifen metabolism. These findings suggest the importance of pharmacogenomics research in our understanding of the efficacy of adjuvant therapies. However, the involvement of multiple enzymes in tamoxifen metabolism, dietary factors, ethnic differences in gene frequencies, and patients’ compliance to tamoxifen therapies in studies do present challenges in pharmacogenomics research. Pharmacogenomics could play important roles in mediating the advancement of tamoxifen-based adjuvant therapies. Research efforts should be directed towards the exploration of further SNPs of CYP2D6 that affect tamoxifen metabolism, as well as epigenetic changes in CYP2D6, enabling the design of precision medicine and confirming clinical validity in the use of pharmacogenomics for tamoxifen.

Background Naloxone is a prescription medication that reverses opioid overdoses. Allowing naloxone to be dispensed directly by a pharmacist without an individual prescription under a naloxone standing order (NSO) can expand access. The community-level factors associated with naloxone dispensed under NSO are unknown. Methods Using a dataset comprised of pharmacy reports of naloxone dispensed under NSO from 70% of Massachusetts retail pharmacies, we examined relationships between community-level demographics, rurality, measures of treatment for opioid use disorder, and overdose deaths with naloxone dispensed under NSO per ZIP Code-quarter from 2014 until 2018. We used a multi-variable zero-inflated negative binomial model, assessing odds of any naloxone dispensed under NSO, as well as a multi-variable negative binomial model assessing quantities of naloxone dispensed under NSO. Results From 2014–2018, quantities of naloxone dispensed under NSO and the number of pharmacies dispensing any naloxone under NSO increased over time. However, communities with greater percentages of people with Hispanic ethnicity (aOR 0.91, 95% CI 0.86–0.96 per 5% increase), and rural communities compared to urban communities (aOR 0.81, 95% CI 0.73–0.90) were less likely to dispense any naloxone by NSO. Communities with more individuals treated with buprenorphine dispensed more naloxone under NSO, as did communities with more opioid-related overdose deaths. Conclusion Naloxone dispensing has substantially increased, in part driven by standing orders. A lower likelihood of naloxone being dispensed under NSO in communities with larger Hispanic populations and in more rural communities suggests the need for more equitable access to, and uptake of, lifesaving medications like naloxone.

OBJECTIVES We examined the effect of fluoridation cessation on children's dental caries experience in the Canadian cities of Calgary (cessation in 2011) and Edmonton (still fluoridated). METHODS We used a pre-post cross-sectional design with comparison group. We studied Grade 2 schoolchildren (approximately 7 years old) 7-8 years after fluoridation cessation in Calgary, thus capturing children born after cessation occurred. Data collection included a dental examination conducted in school by calibrated dental hygienists, a questionnaire completed by parents, and fingernail clippings for a small subsample. Our overall analytic approach was twofold. We first examined differences in dental caries experience (deft and DMFT, and smooth surface caries based on defs and DMFS) between Calgary and Edmonton and over time (comparing 2018/2019 data to pre-cessation and early post-cessation surveys in our setting). Second, we evaluated whether differences were likely to reflect fluoridation cessation in Calgary, rather than other factors. RESULTS The prevalence of caries in the primary dentition was significantly higher (P

Goblet cell carcinoid (GCC) is a rare neoplasm of the vermiform appendix and can be mistaken as a typical neuroendocrine tumour (TNET). The natural history of this disease is more aggressive compared to TNETs and requires a more aggressive approach. We report a case of a 37-year-old male who was initially diagnosed with TNET, but subsequently revised as Tang's A GCC. He underwent appendectomy and right hemicolectomy. Aside from a persistently elevated carcinoembyrogenic antigen (CEA) result, his 18F-fluorodeoxyglucose (FDG) PET/CT and a 68-Gallium DOTATATE PET/CT scan showed no FDG or DOTATATE avid lesions.

Background: The objective of this study is, to describe patterns (or “classes”) used latent class analysis (LCA) to examine patterns of drug use profiles among people who inject drugs (PWIDs) then ...

Background: HIV testing plays an important role in any public health strategy for reducing HIV transmission and controlling HIV/AIDS among people who inject drugs (PWIDs). It is important to clarif...

An adrenal mass can be a diagnostic challenge as it is not easy to differentiate the adrenal glands from other adrenal pseudotumours with only radio-imaging. We report a 28-year-old patient who was diagnosed radiologically as an adrenal cortical carcinoma after he presented with abdominal pain and fullness. Biochemically, he demonstrated secondary hyperaldosteronism. Intra-operatively there was a huge mass, inferior to a normal right adrenal, which was histopathologically proven to be a dedifferentiated liposarcoma.

Purpose To assess whether working in preschools increases the risk of hearing-related symptoms and whether age, occupational noise, and stressful working conditions affect the risk. Methods Questionnaire data on hearing-related symptoms were analysed in women aged 24–65 (4718 preschool teachers, and 4122 randomly selected general population controls). Prevalence and risk ratio (RR) of self-reported hearing loss, tinnitus, difficulty perceiving speech, hyperacusis and sound-induced auditory fatigue were assessed by comparing the cohorts in relation to age and self-reported occupational noise and stressful working conditions (effort–reward imbalance and emotional demands). RR was calculated using log-binomial regression models adjusted for age, education, income, smoking, hearing protection, and leisure noise. Incidence rates and incidence rate ratios (IRR) were calculated for retrospectively reported onset of all symptoms except sound-induced auditory fatigue. Results Compared to the controls, preschool teachers had overall more than twofold RR of sound-induced auditory fatigue (RR 2.4, 95% confidence interval 2.2–2.5) and hyperacusis (RR 2.3, 2.1–2.5) and almost twofold for difficulty perceiving speech (RR 1.9, 1.7–2.0). Preschool teachers had a threefold IRR of hyperacusis (IRR 3.1, 2.8–3.4) and twofold for difficulty perceiving speech (IRR 2.4, 2.2–2.6). Significantly although slightly less increased RR and IRR were observed for hearing loss and tinnitus. RR and IRR were generally still increased for preschool teachers when stratified by age and occupational exposure to noise and stress. Conclusions This large cohort study showed that working as preschool teacher increases the risk of self-reported hearing-related symptoms, indicating a need of preventative measures. Electronic supplementary material The online version of this article (10.1007/s00420-019-01453-0) contains supplementary material, which is available to authorized users.

BACKGROUND: Over the past few decades in the United States, marijuana for medical purposes has become increasingly prevalent. Initial qualitative and epidemiological research suggests that marijuana may be a promising substitute for traditional pharmacotherapies. OBJECTIVES: This qualitative study examined perceptions relating to 1) using medical marijuana in comparison to other prescription medications and 2) user perception of policy issues that limit adoption of medical marijuana use. METHODS: Qualitative interviews were conducted with Rhode Island medical marijuana card holders (N = 25). The interviews followed a semi-structured agenda designed to collect information from participants about their reasons for, and perceptions of, medical marijuana use. All interviews were audio recorded, transcribed verbatim, and de-identified. Qualitative codes were developed from the agenda and emergent topics raised by the participants. RESULTS: Three themes emerged related to medical marijuana use, including (1) comparison of medical marijuana to other medications (i.e., better and/or fewer side effects than prescription medications, improves quality of life), (2) substitution of marijuana for other medications (i.e., in addition to or instead of), and (3) how perception of medical marijuana policy impacts use (i.e., stigma, travel, cost, and lack of instruction regarding use). CONCLUSIONS: Several factors prevent pervasive medical marijuana use, including stigma, cost, and the inability for healthcare providers to relay instructions regarding dosing, strain and method of use. Findings suggest that medical patients consider marijuana to be a viable alternative for opioids and other prescription medications, though certain policy barriers inhibit widespread implementation of marijuana as a treatment option.

Background Associations of the serotonin transporter promoter polymorphism (5-HTTLPR) with bipolar disorder (BPD) and treatment response in bipolar patients were not conclusive. This study not only assessed the association between the 5-HTTLPR and BPD with accumulating relevant studies, but also in the first time evaluated the effect of the 5-HTTLPR on both anti-depressive and anti-manic treatment responses in bipolar patients. Methods PubMed, Embase, PsycINFO, Cochrane Library and Cochrane Control Trials databases were systematically searched before February 2017. This meta-analysis followed the PRISMA guidelines. Results A total of 32 population-based studies (5567 cases and 6993 controls) and 9 family-based studies (837 trios) were finally screened out and statistically joined into a single meta-analysis that revealed an association between S allele and an increased risk of BPD (OR = 1.06, p = .038). Pooled analysis of the 32 population-based studies indicated an association of S-carrier genotypes with an increased risk of BPD (OR = 1.10, p = .029). Meanwhile, the association remained significant in Caucasians (OR = 1.15, p = .004), which could provide an enough power (88%) to detect a significant association. Regarding the treatment response studies, 6 studies reporting the relationship of the 5-HTTLPR in anti-depressive remission rate (1034 patients) and 7 studies reporting in response rate (1098 patients) were included for pooled analyses. We observed a significant association of S-carrier genotypes with a reduced anti-depressive remission rate (OR = 0.64, p = .006) but not with anti-depressive response rate. The association between the 5-HTTLPR with anti-manic response rate was not observed in the included 6 studies (676 patients). Conclusions The present study supported the presence of a marginal but detectable effect of the 5-HTTLPR on susceptibility to BPD. Moreover, the detected association in Caucasian was statistically reliable. Besides, the 5-HTTLPR was identified as a useful predictor for anti-depressive remission but not for anti-depressive or anti-manic response.

Residents of dwellings near railway tunnels may be exposed to noise, which propagates through the tunnel and ground and into the home. Noise radiated into bedrooms may disrupt sleep, which can have negative consequences for physical and mental wellbeing. In this paper, we present a laboratory investigation of the impact of ground-borne railway noise on physiologic and self-reported sleep. Over five consecutive nights, including habituation and control nights, 23 healthy participants were exposed to noise of two different frequency spectra at maximum levels of 35, 40 and 45 dB. Sleep was measured using polysomnography and questionnaires. Heart rate was measured using electrocardiography. Sleep was significantly disturbed, both in terms of physiologic and self-reported measures, during nights with 45 dB noise, although the number and size of effects was modest. No significant differences in overall sleep structure or subjective sleep disturbance and quality were found between control and 35 dB nights. Within 60 s following noise onset, the noise spectrum with higher amplitude frequencies above 100 Hz led to increases in heart rate at noise levels of 35 dB and above, and increased arousal probability at a noise level of 45 dB. The results generally support that the proposed Swedish guideline value of 35 dB maximum noise level indoors may be suitable for protecting against adverse sleep outcomes due to ground-borne railway noise.

Setting Shanghai is a mega city where 39% of the population comprises internal migrants. Objective To examine the different roles played by migrants and permanent residents in the transmission of multidrug-resistant tuberculosis (MDR-TB). Design We conducted a population-based cohort study to assess MDR-TB transmission in Shanghai between 1 January 2009 and 31 December 2012 using genotyping and geospatial analyses. Results A total of 367 MDR-TB cases formed the study cohort. Significant differences between MDR-TB cases who were internal migrants and those who were permanent residents were found with regard to age, sex, region, genetic characteristics and treatment outcomes. Permanent residents had a higher transmission rate than internal migrants (OR 3.36, 95%CI 1.86-6.09). Permanent residents and genotypic clustering cases had similar clusters in central downtown and some parts of suburban areas. Most of the clusters of internal migrants were found in rural areas bordering suburban areas. Clusters of genotypic non-clustering cases showed patterns that closely matched those of internal migrants, suggesting acquired drug resistance in migrants. Conclusion In Shanghai, permanent residents were significantly associated with recent transmission of MDR-TB in central downtown areas. Clustered cases of internal migrants in rural areas were most likely to have contracted MDR-TB through acquired resistance.

Patients with heart failure (HF) often present with signs and symptoms that are often nonspecific and with a wide differential diagnosis, making diagnosis and prognosis of HF by clinical presentation alone challenging. Our knowledge on genetic diversity is rapidly evolving with high-throughput DNA sequencing technology, which makes a great potential for genetic biomarker development. The present review attempts to provide a comprehensive review on the modification of major genetic components in HF patients and to explore the potential application of these components as clinical biomarkers in the diagnosis and in monitoring the progress of HF. The literature search was conducted using six databases, resulting in the inclusion of eighteen studies in the review. The findings of these studies were summarized narratively. An appraisal of the reporting quality of the included studies was conducted using a twelve-item checklist adapted from the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. The findings showed that changes in genetic components in patients with HF compared to healthy controls could be noninvasive diagnostic or prognostic tools for HF with higher specificity and sensitivity in comparison with the traditional biomarkers. This review provided evidence for the potential of developing genetic biomarkers of HF.

Over the next decades, advances in technology and new business practices will challenge a traditionally conservative legal profession. With a focus on the Australian legal profession, this article explores the nature of the challenges and, in particular, considers whether the challenges pose a threat of disruptive innovation. The article aims to add to understanding of how Australian law firms are responding to the challenges by drawing on empirical data that examines the drivers and inhibitors of innovation in Australian law firms, the areas where Australian legal firms are innovating, and the outcomes of their innovation. The article concludes that there is limited evidence of incumbent displacement and that, gradually, the profession is rising to the challenges. Refereed/Peer-reviewed

The extent to which academic research informs both student learning and practice has been repeatedly debated in the management literature. Despite the supposed symbiotic relationship between research, learning, and practice, few studies have sought to identify the potential synergies between these relationships. Moreover, studies investigating these separate relationships have been largely confined to a single discipline. Based on perceptions of 47 practicing managers enrolled in accounting, law and international business courses within an Australian Executive MBA program, our findings suggest that the nature of the ‘gaps’ between research and learning, and research and practice are quite different. Although the value of academic research is recognised, barriers impeding its capacity to more effectively speak to and be utilised by students and practitioners are common to all three disciplinary areas. These barriers do not relate to the ‘use’ of research per se, but rather to the ways in which academic research findings are typically communicated, which thus impacts its ‘usefulness’. Our findings contribute to the literature on the relationship between research, practice, and learning, by suggesting how academic research may be positioned to more effectively impact learning and practice. Refereed/Peer-reviewed

Summary Background Antibody–drug conjugates (ADCs) polatuzumab vedotin (pola) and pinatuzumab vedotin (pina) showed clinical activity and tolerability in phase 1 trials. The aim of this multicentre, open-label, phase 2 study was to compare rituximab plus pola (R-pola) or pina (R-pina) in patients with relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma. Methods In this phase 2 randomised study at 39 investigational sites in six countries, patients were randomly assigned (1:1), by use of a dynamic hierarchical randomisation scheme, to receive R-pola or R-pina (375 mg/m2 rituximab plus 2·4 mg/kg ADCs) every 21 days until disease progression or unacceptable toxicity up to 1 year. Treatment allocations were not masked to the investigator, patients or sponsor after the patients were enrolled and randomly assigned. The primary objectives were safety and tolerability, and antitumour response. The study is registered with ClinicalTrials.gov , number NCT01691898 , and is closed to accrual. Findings 81 patients with diffuse large B-cell lymphoma and 42 with follicular lymphoma were recruited between Sept 27, 2012, and Oct 10, 2013, and were assigned to treatment. 81 patients with diffuse large B-cell lymphoma and 41 patients with follicular lymphoma were eligible for analysis. Of the 42 patients with diffuse large B-cell lymphoma who received R-pina, 25 (60%, 95% CI 43–74) achieved an objective response and 11 (26%, 95% CI 14–42) achieved a complete response. Of the 39 patients in this cohort who received R-pola, 21 (54%, 95% CI 37–70) achieved an objective response, and eight (21%, 95% CI 9–36) achieved a complete response. Of the 21 patients in the follicular lymphoma cohort who received R-pina, 13 (62%, 95% CI 38–82) achieved an objective response, and one (5%, 95% CI 0·1–24) achieved a complete response. Of the 20 patients in this cohort who received R-pola, 14 (70%, 95% CI 46–88) achieved an objective response, and nine (45%, 95% CI 23–68) achieved a complete response. In the diffuse large B-cell lymphoma cohort, grade 3–5 adverse events occurred in 33 (79%) of 42 patients receiving R-pina (most common were neutropenia [29%] and hyperglycaemia [10%]; nine [21%] grade 5 adverse events, five of which were infection-related), and in 30 (77%) of 39 patients receiving R-pola (most common were neutropenia [23%], anaemia [8%] and diarrhoea [8%]; no grade 5 adverse events). In the follicular lymphoma cohort, grade 3–5 adverse events occurred in 13 (62%) of 21 patients receiving R-pina (most common were neutropenia [29%] and hyperglycaemia [14%]; no grade 5 adverse events) and in ten (50%) of 20 patients receiving R-pola (most common were neutropenia [15%] and diarrhoea [10%]; one grade 5 adverse event). Interpretation R-pina and R-pola are potential treatment options in patients with relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma. Pola was selected by the study funder for further development in non-Hodgkin lymphoma, partly because of longer durations of response than pina, and an overall benefit–risk favouring R-pola. Funding F Hoffmann-La Roche.

Despite a number of failed attempts at creating a binding instrument governing the responsibilities of transnational corporations, the United Nations has established an open-ended intergovernmental working group (OEIWG) mandated to “elaborate an international legally binding instrument to regulate, in international human rights law, the activities of transnational corporations and other business enterprises.” The OEIWG will face many questions, including those related to (1) the scope of the rights the instrument will protect; (2) the range of businesses it will govern; (3) the obligations that it will impose on states vis-à-vis transnational corporations and their related entities; (4) whether it will apply directly to transnational corporations; (5) the array of remedies that the instrument might provide to those who have been harmed by breach; and (6) the fora and form of dispute resolution recommended for enforcement. Although all 6 of the questions above are intertwined, this chapter will focus upon matters arising under questions (5) and (6). This chapter will consider and evaluate three potential enforcement options: (1) alignment between the international instrument developed by the OEIWG and domestic enforcement methods; (2) international mediation and arbitration; and (3) the creation of an international court. The chapter will also consider whether the variety of powers that the relevant enforcement body has should include powers to punish misconduct as well as compensate those harmed by misconduct.

Anemia is a decrease in the total amount of red blood cells (RBCs) or hemoglobin in the blood or both which results in a lowered ability of the blood to carry oxygen. According to a 2008 WHO report indicate that more than half of the world’s preschool-age children (56.3%) reside in countries where anemia is a severe public health problem. In sub-Saharan Africa, it is a severe public health problem among preschool-age children. In this region, much of the national prevalence is estimated to be above 40% among this age group. In Ethiopia, more than 44% of under-five children are anemic. Furthermore, a 2016 report national-level indicates even there was intervention the prevalence increased significantly to 72.3%. It means that the prevalence of anemia is still at the highest public health problem in Ethiopia. The Objectives of the study is to assess the prevalence of anemia and associated factors among under-five children attending the pediatrics outpatient department in Asella teaching and referral Hospital from June 2018 to October 30, 2018. An Institutional based cross-sectional study was conducted by non-probability convenience sampling technique; 338 children were selected. The results of the study showed that the overall prevalence of anemia among under-five children was 36.7%, around 21(6.2%) of them were found to be severely anemic, whereas 37 (10.9%) were moderately anemic. Factors like child’s age [AOR=2.36, 95%CI (1.18, 3.74)] and birth intervals [AOR=3.31, 95%CI (1.17, 3.6)], were associated with anemia. Anemia remains a common health problem in the study area among under-five children and further studies are needed to focus on etiologies and interventions.

Background As a response to mounting overdose fatalities, cross-agency outreach efforts have emerged to reduce future risk among overdose survivors. We aimed to characterize such programs in Massachusetts, with focus on team composition, approach, services provided, and funding. Methods We conducted a two-phase cross-sectional survey of public health and safety providers in Massachusetts. Providers in all 351 municipalities received a screening survey. Those with programs received a second, detailed survey. We analyzed responses using descriptive statistics. Results As of July 2019, 44 % (156/351) of Massachusetts municipalities reported post-overdose outreach programs, with 75 % (104/138) formed between 2016−2019. Teams conducted home-based outreach 1–3 days following overdose events. Police departments typically supplied location information on overdose events (99 %, 136/138) and commonly participated in outreach visits (86 %, 118/138) alongside public health personnel, usually from community-based organizations. Teams provided or made referrals to services including inpatient addiction treatment, recovery support, outpatient medication, overdose prevention education, and naloxone. Some programs deployed law enforcement tools, including pre-visit warrant queries (57 %, 79/138), which occasionally led to arrest (11 %, 9/79). Many programs (81 %, 112/138) assisted families with involuntary commitment to treatment – although this was usually considered an option of last resort. Most programs were grant-funded (76 %, 104/136) and engaged in cross-municipal collaboration (94 %, 130/138). Conclusions Post-overdose outreach programs have expanded, typically as collaborations between police and public health. Further research is needed to better understand the implications of involving police and to determine best practices for increasing engagement in treatment and harm reduction services and reduce subsequent overdose.

Objective Low productivity while at work (presenteeism) has been reported to produce significant cost excesses for organizations and economies. However, many of these reports have been based on estimates drawn from self-report instruments that are not supported by evidence showing their efficacy. Thus, the aim of this study was to assess associations between responses to leading self-report tests of presenteeism and self-recorded on-the-job productivity. Methods Health care worker self-ratings of productivity were taken from a questionnaire that contained the key item from each presenteeism instrument. Productivity levels were drawn from employee reported daily work activity logs. Results Test-based productivity estimates did not show strong associations with daily recordings of work activity. Conclusions Associations were too low to recommend any test as a proxy measure for reported productivity. It is suggested that objective measures of work output be explored.

Mosunetuzumab, a T-cell dependent bispecific antibody that binds CD3 and CD20 to drive T-cell mediated B-cell killing, is currently being tested in non-Hodgkin lymphoma. However, potent immune stimulation with T-cell directed therapies poses the risk of cytokine release syndrome, potentially limiting dose and utility. To understand mechanisms behind safety and efficacy and explore safety mitigation strategies, we developed a novel mechanistic model of immune and antitumor responses to the T-cell bispecifics (mosunetuzumab and blinatumomab), including the dynamics of B- and T-lymphocytes in circulation, lymphoid tissues, and tumor. The model was developed and validated using mosunetuzumab nonclinical and blinatumomab clinical data. Simulations delineated mechanisms contributing to observed cell and cytokine (IL6) dynamics and predicted that initial step-fractionated dosing limits systemic T-cell activation and cytokine release without compromising tumor response. These results supported a change to a step-fractionated treatment schedule of mosunetuzumab in the ongoing Phase I clinical trial, enabling safer administration of higher doses.

Background Pin2/ TRF 1‐interacting protein, PinX1, was previously identified as a tumor suppressor. Here, we discovered a novel transcript variant of mP inX1 (mouse PinX1), mP inX1t (mouse PinX1t), in embryonic stem cells ( ESC s). The aims of this investigation were (1) to detect the presence of mP inX1 and mP inX1t in ESC s and their differentiation derivatives; (2) to investigate the role of mP inX1 and mP inX1t on regulating the characteristics of undifferentiated ESC s and the cardiac differentiation of ESC s; (3) to elucidate the molecular mechanisms of how mP inX1 and mP inX1t regulate the cardiac differentiation of ESCs. Methods and Results By 5′ rapid amplification of cDNA ends, 3′ rapid amplification of cDNA ends, and polysome fractionation followed by reverse transcription–polymerase chain reaction, mP inX1t transcript was confirmed to be an intact mRNA that is actively translated. Western blot confirmed the existence of mP inX1t protein. Overexpression or knockdown of mP inX1 (both decreased mP inX1t expression) both decreased while overexpression of mP inX1t increased the cardiac differentiation of ESC s. Although both mP inX1 and mP inX1t proteins were found to bind to cardiac transcription factor mRNA s, only mP inX1t protein but not mP inX1 protein was found to bind to nucleoporin 133 protein, a nuclear pore complex component. In addition, mP inX1t‐containing cells were found to have a higher cytosol‐to‐nucleus ratio of cardiac transcription factor mRNA s when compared with that in the control cells. Our data suggested that mP inX1t may positively regulate cardiac differentiation by enhancing export of cardiac transcription factor mRNA s through interacting with nucleoporin 133. Conclusions We discovered a novel transcript variant of mP inX1, the mP inX1t, which positively regulates the cardiac differentiation of ESC s.

Background and objectives Through the use of an experimental design with a baseline and post intervention, the aim of this study was to investigate the effectiveness of a psychological intervention in increasing public health and communication skills for caregivers. Methods This randomized controlled trial was designed in Razi Hospital in Tehran, Iran. A sample size of 90 participants was evenly divided into intervention and control groups. The intervention group was given routine treatments and also participated in planned educational sessions. The planned educational program was implemented in 10 group sessions over a period of 5 weeks. Each session lasted 45–60 min. The outcome measures were: (1) improvement in the caregiver's general health as measured by the changes in their General Health Questionnaire (GHQ) scores taken at baseline and post intervention and (2) changes in the caregiver's communication skills, measured by the communication skills questionnaire taken at baseline and after 3 months. Results An independent samples t-test revealed that there was a significant difference between the two groups in the mean scores of communication skill at baseline (P Conclusion Results of our study confirm that providing education on effective communication skills can be an effective, cost-efficient, and convenient strategy to reduce the psychological complications for caregivers and improve the care of patients living with schizophrenia.

The Environmental Protection Department (EPD) of the Government of Hong Kong Special Administrative Region is the owner and project proponent of the Sludge Treatment Facility (STF), a facility dedicated to treating sewage sludge. The Contract to design, build and operate the STF was awarded to VW-VES (HK) Limited (a subsidiary of Veolia), and Jacobs China Limited was appointed to act as the Employer’s Representative in October 2010. The construction of the STF was substantially completed in 2015 and it was put into operation on 1 April 2015. The STF, featuring state-of-art incineration technology, provides for a sustainable sewage sludge treatment solution, with a view to maximizing the reduction on disposal of the sludge to landfill. In consideration of the diminishing landfill space, the STF is designed to have a capacity of treating 2,000 tonnes per day, thereby reducing the mass of the sludge by 90%. The STF is also on another green mission – to convert waste into renewable energy harnessing the heat from the incineration process to generate electricity, resulting in the provision of all power for the daily on-site operations, with the design allowing the export of surplus power to the local grid. The STF also includes facilities for the production of both process and potable water as well as being able to treat all waste water for use on-site. This adopted design makes the STF a self-sustainable facility with no incoming water supply and outfall for wastewater. As well as the abovementioned technical aspects, the STF serves as a community facility. An environmental education centre located inside the STF showcases the technology used within the STF to convert waste-to-energy, and also to promote public awareness of various environmental issues in Hong Kong. There is also a diverse range of recreational and open areas (e.g. spa and garden) for the public to experience the benefits of waste-to-energy. Since the opening of the EEC on 29 June 2016, the number of visitors has exceeded 72,000.

Background: The use of a clonal master engineered induced pluripotent stem cell (iPSC) line as a renewable source for the mass production of immune effector cells offers distinct advantages over existing patient (pt)- and donor-derived cell-based cancer immunotherapy approaches, including off-the-shelf availability for broad pt access and multi-dose administration. FT596 is an iPSC-derived, off-the-shelf, CD19-directed chimeric antigen receptor (CAR) natural killer (NK) cell therapy capable of multi-antigen targeting in combination with monoclonal antibody (mAb) therapies. FT596 has three anti-tumor modalities: (1) a proprietary CD19-targeting CAR; (2) a novel high-affinity, non-cleavable CD16 Fc receptor that enables tumor targeting and enhanced antibody-dependent cell cytotoxicity in combination with a therapeutic mAb; and (3) IL-15/IL-15 receptor fusion promoting cytokine-autonomous persistence. Preclinical in vivo models of leukemia and lymphoma demonstrate potent CAR-mediated efficacy of FT596 against CD19+ tumor cells and activity against both CD19+ and CD19- tumor cells when combined with the anti-CD20 agent rituximab (Goodridge et al. 2019). Methods: FT596 is being investigated in a multicenter, Phase I clinical trial in pts with relapsed/refractory (R/R) B-cell lymphomas (BCLs) and chronic lymphocytic leukemia (ClinicalTrials.gov: NCT04245722). Conditioning chemotherapy (fludarabine 30 mg/m 2 and cyclophosphamide 500 mg/m 2 on Days -5 to -3) is administered followed by a single dose of FT596 as monotherapy (Regimen A) or combined with rituximab (R) 375 mg/m 2 (Regimen B1) or obinutuzumab 1000 mg/m 2 (Regimen B2) on Day -4. FT596 single-dose levels between 30 and 900 million cells are being tested. Pts experiencing clinical benefit may receive a second cycle of conditioning followed by a single dose of FT596 with FDA approval (Cycle 2). Primary objectives are to determine the recommended Phase II dose of FT596 and safety and tolerability. Additional key objectives include preliminary anti-tumor activity per the Lugano Classification, pharmacokinetics, and anti-product immunogenicity. Results: As of a data cutoff date of 25 June 2021, 20 pts with R/R BCL (12 with aggressive histology, 8 indolent) were treated in dose escalation with FT596, including 10 in Regimen A and 10 in Regimen B1 (3 with 30 million cells, 4 with 90 million cells, and 3 with 300 million cells in each regimen). Pts had received a median of 4 prior therapies, with 7 having received CAR T-cell therapy and 5 with autologous stem cell transplant. Ten of 20 pts were refractory to last prior therapy. No dose-limiting toxicities were reported with either regimen. No graft-versus-host disease (GvHD) or immune effector cell-associated neurotoxicity syndrome (ICANS) were observed. Two cases of cytokine release syndrome (CRS) were reported (one Gr 1 and one Gr 2). The most common treatment-emergent adverse events of any grade were neutrophil count decreased (85%), nausea (75%), anemia (50%), WBC count decreased (45%), fatigue and platelet count decreased (40% each), and peripheral edema (35%). No B- or T-cell mediated anti-product responses were observed. Of 17 efficacy-evaluable pts, 5 of 8 in Regimen A and 4 of 9 in Regimen B achieved an objective response after the first FT596 treatment cycle. At single-dose levels of ≥90 million cells, 8 of 11 efficacy-evaluable pts achieved an objective response, including 7 complete responses (CR). Of 4 pts with prior CAR T-cell therapy treated at ≥90 million cells, 2 achieved CR. The FDA approved all requests for FT596 retreatment. Seven of 9 responders received Cycle 2; 1 pt with CR elected not to receive Cycle 2, and 1 pt with partial response (PR) experienced disease progression prior to initiation of Cycle 2. Five pts (4 with CR, 1 with PR after Cycle 1) completed Cycle 2, and 2 pts initiated Cycle 2 after data cutoff. CR was maintained after Cycle 2 in all 4 pts with CR, while the 1 pt with PR experienced a deepening PR after Cycle 2. No CRS, ICANS, or GvHD were reported with Cycle 2. Conclusions: FT596 monotherapy or in combination with R was well tolerated and demonstrated activity in pts with R/R BCL, including in pts previously treated with CAR T-cell therapy. Administration of a second FT596 treatment cycle was well tolerated with evidence of continuing clinical benefit. Dose escalation of FT596 is ongoing. Updated clinical and translational data will be presented at the conference. Disclosures Bachanova: Gamida Cell: Membership on an entity's Board of Directors or advisory committees, Research Funding; KaryoPharma: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; FATE: Membership on an entity's Board of Directors or advisory committees, Research Funding. Ghobadi: Wugen: Consultancy; Atara: Consultancy; Amgen: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; Celgene: Consultancy. Patel: Kite Pharma: Consultancy, Speakers Bureau; Janssen: Consultancy; Genentech: Consultancy; Bristol Myers Squibb: Consultancy, Speakers Bureau; BeiGene: Consultancy; Morphosys: Consultancy; Pharmacyclics: Consultancy; Abbvie: Consultancy; TG Therapeutics: Consultancy, Speakers Bureau; MEI Pharma: Consultancy; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; ADC Therapeutics: Consultancy; Lilly: Consultancy. Park: Kite Pharma: Consultancy; BMS: Consultancy; Artiva: Consultancy; Minerva: Consultancy; Curocel: Consultancy; Amgen: Consultancy; Affyimmune: Consultancy; Kura Oncology: Consultancy; Servier: Consultancy; Autolus: Consultancy; Intellia: Consultancy; Innate Pharma: Consultancy; PrecisionBio: Consultancy; Novartis: Consultancy. Flinn: Gilead Sciences: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; TG Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Nurix Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Rhizen Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Karyopharm Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Kite, a Gilead Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; AstraZeneca: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Forty Seven: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; MorphoSys: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; AbbVie: Consultancy, Other: All Consultancy and Research Funding payments made to Sarah Cannon Research Institute, Research Funding; Constellation Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Teva: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Curis: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Forma Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Roche: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; IGM Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Incyte: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Acerta Pharma: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Iksuda Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; ArQule: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Genentech: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Juno Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Verastem: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Unum Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Agios: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Novartis: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Seagen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Pfizer: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Janssen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Calithera Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Loxo: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Celgene: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Great Point Partners: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Merck: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Infinity Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Takeda: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; BeiGene: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Portola Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Century Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Trillium Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Triphase Research & Development Corp.: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Hutchison MediPharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Vincerx Pharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Sarah Cannon Research Institute: Current Employment; Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Seagen: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Unum Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute, Research Funding; Johnson & Johnson: Current holder of individual stocks in a privately-held company; Seattle Genetics: Research Funding. Shah: Fate Therapeutics, Inc.: Current Employment. Wong: Fate Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company. Bickers: Fate Therapeutics, Inc.: Current Employment. Szabo: Fate Therapeutics, Inc: Current Employment. Wong: BMS: Current equity holder in publicly-traded company; Fate Therapeutics, Inc: Current Employment. Valamehr: Fate Therapeutics, Inc.: Current Employment. Atwal: Fate Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company. Chu: Gilead: Current equity holder in publicly-traded company; Roche: Current equity holder in publicly-traded company; Fate Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company. Elstrom: Fate Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company; BeiGene: Current equity holder in publicly-traded company. Strati: Astrazeneca-Acerta: Research Funding; Roche-Genentech: Consultancy.

Background: Allogeneic natural killer (NK) cell therapies have documented anti-tumor activity in patients with relapsed/refractory (R/R) hematologic malignancies, including B-cell lymphoma (BCL), and may offer an improved safety profile characterized by the absence of cytokine release syndrome (CRS) and neurologic toxicity compared with T-cell therapies (Liu et al. 2020). However, limited availability of suitable donors, relatively short in vivo persistence, and manufacturing constraints limiting the ability to consistently deliver multiple doses remain barriers to maximizing the clinical benefit of NK cell therapy. FT516 is a first-of-kind, off-the-shelf, NK cell therapy manufactured from a clonal master engineered induced pluripotent stem cell (iPSC) line, which can be used as a renewable source for the mass production of NK cells for multi-dose treatment and immediate patient access. FT516 expresses a novel high-affinity, non-cleavable CD16 (hnCD16) Fc receptor, which has been demonstrated preclinically to maximize antibody-dependent cellular cytotoxicity in combination with an anti-CD20 monoclonal antibody (Zhu et al. 2020). Methods: Primary objectives of the study are to determine the recommended Phase II dose of FT516 in combination with rituximab (R) or obinutuzumab (G) in R/R BCL and to evaluate safety and tolerability in patients (pts) with R/R BCL. Key secondary objectives include evaluation of FT516 anti-tumor activity by Lugano Classification and pharmacokinetics when combined with R or G in R/R BCL. The ongoing dose-escalation stage assesses FT516 for up to 2 cycles, each consisting of 3 days of conditioning chemotherapy (cyclophosphamide [CY] 500 mg/m 2 and fludarabine [FLU] 30 mg/m 2), a single-dose of R (375 mg/m 2), and 3 weekly doses of FT516 (30-900 million cells per dose) each with IL-2 support (6 MIU). FT516 may be administered in the outpatient setting with no mandatory hospitalization. Following dose escalation, further investigation of safety and efficacy will be conducted as follows: FT516 + R or G following FLU/CY in pts with R/R diffuse large B-cell lymphoma (DLBCL) or R/R follicular lymphoma (FL) who have not received prior CAR T-cell therapy; FT516 + R following FLU/CY in pts with R/R BCL who have previously received CAR T-cell therapy; and FT516 + R following bendamustine. Results: As of 07 July 2021, 13 pts (2 at 30 million cells per dose, 4 at 90 million cells per dose, and 7 at 300 million cells per dose) were enrolled and had at least 3 months of follow-up or discontinued. Pts had DLBCL, including transformed indolent (7 pts), high-grade BCL (HGBCL, 3 pts), low-grade FL (2 pts), or marginal zone lymphoma (1 pt), and received a median of 3 prior lines of therapy and a median of 2 prior lines containing CD20-targeted therapy. Ten of 13 pts received both planned treatment cycles (6 doses of FT516); 3 pts discontinued after a single cycle due to disease progression. No dose-limiting toxicities, FT516-related serious adverse events, or FT516-related Grade ≥3 adverse events (AEs) were observed. No CRS, immune effector cell-associated neurotoxicity syndrome (ICANS), or graft-versus-host disease (GvHD) of any grade were reported. Grade ≥3 AEs occurring in ≥2 pts were neutrophil count decreased (6 pts), neutropenia (5 pts), febrile neutropenia (3 pts), and thrombocytopenia (2 pts). Eight of the 11 pts (72%) treated with ≥90 million FT516 cells achieved an objective response. Seven pts achieved complete response (CR), including 2 pts whose disease progressed following treatment with autologous CD19 CAR T-cell therapy. Two pts treated at the lowest dose of 30 million FT516 cells experienced progressive disease. Of the 8 responders, 5 continue in remission at between 4.6 and 9.5 months. One pt with primary refractory triple-hit HGBCL that had progressed after 7 prior regimens, including CAR T-cell therapy, continues in CR with minimal residual disease negativity by local ctDNA analysis 4.9 months from initiation of FT516 treatment. Conclusions: Administration of up to 6 doses of FT516 cells in combination with R appears safe and tolerable up to 300 million cells per dose, without CRS, ICANS, or GvHD. Deep responses were observed in heavily pretreated pts, with several with ongoing CR at data cutoff. Updated clinical and translational results of ongoing dose escalation will be presented at the conference. Disclosures Patel: Pharmacyclics: Consultancy; Morphosys: Consultancy; Bristol Myers Squibb: Consultancy, Speakers Bureau; BeiGene: Consultancy; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; Genentech: Consultancy; Janssen: Consultancy; Kite Pharma: Consultancy, Speakers Bureau; ADC Therapeutics: Consultancy; Abbvie: Consultancy; TG Therapeutics: Consultancy, Speakers Bureau; MEI Pharma: Consultancy; Lilly: Consultancy. Bachanova: Gamida Cell: Membership on an entity's Board of Directors or advisory committees, Research Funding; KaryoPharma: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; FATE: Membership on an entity's Board of Directors or advisory committees, Research Funding. Goodman: EUSA Pharma: Consultancy, Honoraria; Seattle Genetics: Consultancy, Speakers Bureau. Pagel: Pharmacyclics/AbbVie: Consultancy; MEI Pharma: Consultancy; AstraZeneca: Consultancy; Kite, a Gilead Company: Consultancy; Gilead: Consultancy; Actinium Pharmaceuticals: Consultancy; BeiGene: Consultancy; Epizyme: Consultancy; Incyte/MorphoSys: Consultancy. Griffis: Fate Therapeutics, Inc.: Current Employment. Anderson: Fate Therapeutics, Inc.: Consultancy. Atwal: Fate Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company. Bickers: Fate Therapeutics, Inc.: Current Employment. Szabo: Fate Therapeutics, Inc: Current Employment. Wong: BMS: Current equity holder in publicly-traded company; Fate Therapeutics, Inc: Current Employment. Chu: Gilead: Current equity holder in publicly-traded company; Roche: Current equity holder in publicly-traded company; Fate Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company. Elstrom: Fate Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company; BeiGene: Current equity holder in publicly-traded company. Strati: Roche-Genentech: Consultancy; Astrazeneca-Acerta: Research Funding.

Purpose Drawing on “Strategic Alliance” literature and qualitative research methods, the purpose of this study is to examine the initiation and operations phases of the relationship between Australian litigation funders and class law firms. The initiation phase examines factors such as complementarity between needs and assets compatibility between the funder and the class law firm goals of the alliance trust and alliance structure. The operations phase considers factors such as governance, communication and risk management and accountability. Because of its focus on the fairness of settlement, case law provides limited understanding of the drivers of the class law firm and funder relationship. An “inside look” of how the funder-law firm is initiated and made operational provides a more accurate picture and has important implications for the management of the ethical issues that arise during the course of that relationship. Design/methodology/approach This paper is a content analysis and contains qualitative interviews. Findings The strategic alliance between class law firms and litigation funders has evolved within an institutional climate that has acknowledged the benefits that the alliance can bring to the conduct of class actions. That same institutional environment has led to an alliance which is informal and transactionally oriented, where each of the parties maintains a demarcation in function. Although they share aspects of the strategic management of class actions, funders continue to be diligent monitors of class law firms, and class law firms continue to advance the legal rights of class members. Research limitations/implications It is observed that the size of the sample is small driven by a number of market participants. Practical implications The paper confirms that the litigation funder–law firm strategic alliance works well as a result of institutional constraints. Social implications Each of the alliance partners was keen to ensure that neither they nor their partner acted in a way which might attract judicial disapproval. Each also believed that they played a positive role in promoting class member interests, albeit that their primary motivation was to earn fees or a commission. The success of the alliance between class law firms and litigation funders has substantially improved access to justice in Australia for small claims holders. Originality/value The paper provides insight into a strategic alliance which is formed primarily for the benefit of third parties. This is one of the first papers to consider the litigation funder–law firm relationship through the lens of strategic alliance literature.

Modern service-oriented applications forgo semantically rich protocols and middleware when composing services. Instead, they embrace the loosely-coupled development and deployment of services that communicate via simple network protocols. Even though these applications do expose interfaces that are higher-order in spirit, the simplicity of the network protocols forces them to rely on brittle low-level encodings. To bridge the apparent semantic gap, programmers introduce ad-hoc and error-prone defensive code. Inspired by Design by Contract, we choose a different route to bridge this gap. We introduce Whip, a contract system for modern services. Whip (i) provides programmers with a higher-order contract language tailored to the needs of modern services; and (ii) monitors services at run time to detect services that do not live up to their advertised interfaces. Contract monitoring is local to a service. Services are treated as black boxes, allowing heterogeneous implementation languages without modification to services' code. Thus, Whip does not disturb the loosely coupled nature of modern services.

Despite being a potent hypolipidemic drug, atorvastatin (AS) possesses certain adverse effects. Using AS and an herbal formula (Danshen and Gegen, DG) in combination may achieve potentiated hypolipidemic effects and also reduce its adverse effects. Hence, this study aimed to investigate the efficacy and safety of an AS and DG combination on high-fat diet-induced hyperlipidemia. Treatment outcomes were assessed by measuring parameters including body weight, adipose tissue, liver, total cholesterol, triglyceride, and low-density and high-density lipoprotein cholesterol. Measurements of adverse effects were achieved by determining aspartate aminotransferase (AST), alanine transaminase (ALT), and creatine kinase (CK). Danshen and Gegen, as well as AS alone, reduced body weight, adipose tissue, liver weight, liver fat vacuoles, total liver lipids, total cholesterol, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in high-fat diet-fed mice but increased AST, ALT, and CK. A combination of AS and DG was able to enhance reduced effects on the aforementioned parameters in relation to hyperlipidemia over AS or DG alone. It also reduced the elevation of AST, ALT, and CK induced than by AS or DG alone. Results demonstrated that an AS and DG combination resulted in stronger hypolipidemic effects than with AS or DG alone. Additionally, DG might attenuate adverse effects of AS on the liver and skeletal muscle. Copyright © 2017 John Wiley & Sons, Ltd.

Purpose: Pinatuzumab vedotin is an antibody–drug conjugate with the potent antimicrotubule agent monomethyl auristatin E (MMAE) conjugated to an anti-CD22 antibody via a protease-cleavable linker. This phase I study determined its recommended phase II dose (RP2D) and evaluated its safety, tolerability, and antitumor activity alone and with rituximab in relapsed/refractory (r/r) non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Experimental Design: Patients received escalating doses of pinatuzumab vedotin every 21 days. Clinical activity at the RP2D alone or with rituximab was evaluated in r/r diffuse large B-cell lymphoma (DLBCL) and r/r indolent NHL (iNHL) patients. Results: Seventy-five patients received single-agent pinatuzumab vedotin. The RP2D was 2.4 mg/kg, based on dose-limiting toxicities (DLT) of grade 4 neutropenia >7 days in 1 of 3 patients and grade 4 neutropenia Conclusions: The RP2D of pinatuzumab vedotin alone and with rituximab was 2.4 mg/kg, which was well tolerated, with encouraging clinical activity in r/r NHL. Clin Cancer Res; 23(5); 1167–76. ©2016 AACR.

Correlations between early and late efficacy endpoints were assessed to identify potential surrogate endpoints for overall survival (OS) or progression-free survival (PFS) with clinical trial-level data in three non-Hodgkin lymphoma (NHL) subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). One hundred and eight phase II–III trials (129 trial arms) in DLBCL, FL, and MCL were identified and included in the database. Correlations between efficacy endpoints were analyzed using weighted linear regression and Pearson’s coefficient of determination (R 2). In newly diagnosed DLBCL, 6-month PFS was strongly correlated with 2-year OS (R 2 = 0.81, 95% confidence interval [CI] 0.51–0.96). Six-month PFS was strongly correlated with 3-year PFS (R 2 = 0.89, 95% CI 0.62–0.96) in FL and was moderately correlated with 2-year OS (R 2 = 0.69, 95% CI 0.40–0.91) in MCL trials. Linear regression determined that a 10% increase in 6-month PFS would yield a 13% ± 1.2% increase in 2-year OS in DLBCL, a 23% ± 1.1% increase in 3-year PFS in FL, or a 6.7% ± 1.0% increase in 2-year OS in MCL. Both 6-month PFS and complete response (CR) rate were moderately correlated with median PFS in FL trials with R 2 = 0.66 (95% CI 0.52–0.98) and R 2 = 0.69 (95% CI 0.22–0.89), respectively. Six-month PFS is a potential surrogate endpoint for 2-year OS in newly diagnosed DLBCL and MCL and for 3-year PFS in FL. Both 6-month PFS and CR rate are potential surrogate endpoints for median PFS in FL patients. Confirmation and validation of these correlations may facilitate early interpretation of NHL trials.

Characteristics and behaviors of early-onset injection drug users are under studied topics in Iran. This study aimed to identify and compare the demographic characteristics as well as the drug using behaviors of early-onset and late-onset injection drug users in Kermanshah, West Iran.In this cross-sectional study using snowball and convenience sampling, we recruited 450 people during the Fall of 2014 from two drop in centers in Kermanshah, Iran. We collected data through face-to-face interviews. Early-onset injection is defined as whether the person reported their first injection at 22 years of age or younger. Subsequently, late-onset injection is defined as 23 years of age or older. We compared the characteristics of the two groups through both univariate and multiple logistic analyses.Overall, 54% (CI 95%: 44.3%, 62.2%) were early injectors. After controlling for low socioeconomic status, initiation of drug use at a young age, multiple drug use and methamphetamine use were all significantly associated with a higher likelihood of early-onset injection. Additionally, early-onset injection was associated with recent syringe borrowing (OR = 2.6, p = 0.001), recent syringe lending (OR = 1.4, p = 0.01), recent cooker sharing (OR = 3.2, p = 0.01) and injecting two or more times a day (OR = 2.2, p = 0.04).Early-onset injectors were more likely to report a lower socioeconomic status, initiation of first drug use at a younger age, using methamphetamine alongside polydrug use, and engaging in higher risk taking behaviors like borrowing needles. With these associations, the study emphasizes the need for drug-prevention programs to focus on the transition to injection drug use at younger ages.

Understanding and increasing awareness on individual risk for HIV infection as well as HIV risk perception’s effects on different behavioral outcomes for people who inject drugs (PWID) is important for policymaking and planning purposes. The objectives of the present study were to determine whether HIV risk perception was associated with greater injection and sexual risk-taking behaviors among PWIDs. We surveyed 460 PWID in Kermanshah regarding their demographic characteristics, sexual risk behaviors, HIV risk perception, and drug-related risk behaviors in the month prior to the study. Three classes of HIV risk perception were identified using ordinal regression to determine factors associated with HIV risk perception. Study participants were categorized as follows: “low” (n = 100, 22%), “moderate” (n = 150, 32%), and “high” (n = 210, 46%) risk perception for becoming infected with HIV. The odds of categorizing as “high” risk for HIV was significantly greater in PWID that reported unprotected sex (adjusted odds ratio (AOR) 2.4, p value 0.02), receptive syringe sharing (AOR 1.8, p value 0.01), and multiple sex partners (AOR 1.4, p value 0.03). PWID who reported unprotected sex had 2.7 times the odds of “high” risk perception when compared to PWID with “low” risk perception. Findings show that PWID could rate their HIV risk with acceptable accuracy. Additionally, perceived HIV risk was associated with many risk factors for transmission of HIV, emphasizing the importance of developing targeted prevention and harm reduction programs for all domains of risk behaviors, both sexual and drug-related use.

Background: Autologous T cells engineered to express a chimeric antigen receptor (CAR) targeting the B-cell lineage antigen CD19 (CAR19) in patients with relapsed/refractory (r/r) aggressive B-cell lymphomas (BCL) and pre-B acute lymphoblastic leukemia (B-ALL) have resulted in transformative improvements in clinical outcomes. However, there remain significant limitations concerning autologous CAR19 T cell manufacturing, including dysfunctional starting material, lack of product consistency and purity following genetic engineering, manufacturing timelines that necessitate the administration of bridging therapy in patients with aggressive disease, and insufficient quantities of CAR19 T cells, especially in severely cytopenic patients, to allow for more than single-dose administration routinely. The ability to consistently administer more than a single dose of CAR19 T cells enables dosing schedules that may reduce the risk of potentially life-threatening toxicities such as cytokine release syndrome and neurotoxicity, while maintaining or improving the depth and durability of anti-tumor responses. FT819 is a first-of-kind, off-the-shelf CAR19 T cell product candidate derived from a clonal master engineered induced pluripotent stem cell (iPSC) line, which can be used as a renewable source for the mass production of off-the-shelf CAR T cells for broad patient access. FT819 is engineered with the following features designed to improve the safety and efficacy of CAR T cell therapy: a novel 1XX CAR signaling domain, which has been shown to extend T cell effector function without eliciting exhaustion; integration of the CAR transgene directly into the T cell receptor alpha constant (TRAC) locus, which has been shown to promote uniform CAR expression and enhanced T cell potency; and complete bi-allelic disruption of T cell receptor (TCR) expression for the prevention of graft-versus-host disease (GVHD). FT819 has demonstrated antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of donor-derived CAR T cells, and persists and maintains tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia (Mandal et al. 2020). The properties of FT819 and its ability to improve outcomes of patients with B-cell malignancies warrants further clinical investigation. Study Design and Methods: This study is a multicenter, Phase I clinical trial of FT819 in patients with r/r B-cell malignancies, including BCL, chronic lymphocytic leukemia (CLL), and B-ALL. The primary objective of the trial is to determine the recommended Phase II dose of FT819. Key secondary objectives include evaluation of FT819 safety and tolerability, anti-tumor activity, and pharmacokinetics (PK). Exploratory objectives include characterization of FT819 pharmacodynamics as assessed by peripheral blood biomarkers, and by phenotypic and genetic characterization of the tumor microenvironment from paired pre- and post-treatment tumor biopsies. The dose-escalation part of the trial utilizes a 3+3 dose-escalation design to identify the maximum tolerated dose for BCL, CLL, and B-ALL. The dose-expansion part of the trial is designed to further characterize the safety, efficacy, and PK of FT819 in multiple indications. Up to a maximum of 300 patients will be enrolled. The trial will test up to four FT819 dose levels ranging from 30 to 900 million cells. Three FT819 dosing regimens each will be tested for BCL, CLL, and B-ALL: Regimen A, FT819 administered as a single dose; Regimen A1, FT819 administered as a single dose in combination with interleukin (IL)-2; and Regimen B, FT819 administered as fractionated doses on Days 1, 3, and 5. Lympho-conditioning will consist of three consecutive days of fludarabine and cyclophosphamide administered prior to the first dose of FT819. Key inclusion criteria include r/r disease after standard approved therapies, documented CD19 expression, and adequate organ function. Key exclusion criteria include ongoing immunosuppression such as systemic GVHD therapy, prior allograft organ transplant, active central nervous system involvement of disease, and known allergy to FT819 components. The trial is expected to begin patient recruitment in 2020. Disclosures Park: Novartis: Consultancy; Fate Therapeutics: Research Funding; Amgen: Consultancy, Research Funding; Genentech/Roche: Research Funding; Kite: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; GSK: Consultancy; Autolus: Consultancy, Research Funding; Intellia: Consultancy; Minverva: Consultancy; Takeda: Consultancy, Research Funding; AstraZeneca: Consultancy; Servier: Consultancy, Research Funding; Allogene: Consultancy; Juno Therapeutics: Research Funding; Artiva: Membership on an entity's Board of Directors or advisory committees. Jain:Pfizer: Research Funding; ADC Therapeutics: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Aprea Therapeutics: Research Funding; BeiGene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Precision Bioscienes: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Fate Therapeutics: Research Funding; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellectis: Research Funding; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. McGuirk:Bellicum Pharmaceutical: Research Funding; Gamida Cell: Research Funding; Astellas: Research Funding; Pluristem Ltd: Research Funding; Novartis: Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Kite Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; Fresenius Biotech: Research Funding; Allo Vir: Consultancy, Honoraria, Research Funding. Diaz:Fate Therapeutics, Inc.: Current Employment. Valamehr:Fate Therapeutics, Inc: Current Employment, Current equity holder in publicly-traded company. Chu:Fate Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company; Roche Holding AG: Current equity holder in publicly-traded company. Castro:Kite Pharma: Research Funding; Pharmacyclics: Research Funding; Fate Therapeutics: Research Funding. OffLabel Disclosure: Cyclophosphamide and fludarabine will be used as lympho-conditioning therapy prior to FT819 administration. IL-2 will be administered in order to promote the expansion and function of FT819 as a T-cell product.

A meta-analysis was conducted to evaluate the effect of treatment with angiotensin-converting enzyme inhibitors on the risk of fractures. All the included articleswere retrieved from MEDLINE, EMBASE and the Cochrane Database. Trial eligibility and methodological quality were assessed before data extraction. Relative risk (RR) with corresponding 95% confidence intervals (95% CI) were used to assess the effect. Six case-control studies with11,387,668 participants met the inclusion criteria and were included in the meta-analysis. A small but significant risk effect on fractures was shown in the overall analysis of angiotensin-converting enzyme inhibitor users compared with nonusers (Pooled RR 1.27; 95% CI 1.01-1.60), although a relatively high heterogeneity was found across studies. In the stratified analysis, therewas no statistically significant association in the subgroups of hip fracture (Pooled RR 1.14; 95% CI 0.73-1.76) and the study quality (Pooled RR 1.13; 95% CI 0.89-1.44), while the over 65-year-old angiotensin-converting enzyme inhibitor users showed a stronger risk effect on fractures (Pooled RR 2.06; 95% CI 1.53-3.17). Moreover, age was found to be contributed a large part of the high heterogeneity across the included studies. This study demonstrated that the use of angiotensin-converting enzyme inhibitors might have a small but significant risk effect on fractures, especially for the over 65-year-old users. These results should be interpreted with caution as the relatively high heterogeneity across studies. Additional multiple observational studies and high quality data from randomized controlled trials are needed to confirm these findings.

Introduction Reslizumab is the second biologic available targeting Interleukin 5 (IL5), for the management of severe eosinophilic asthma. We use it in patients who have failed to respond to mepolizumab or with suspected vasculitis. Aims To determine the efficacy of reslizumab in reducing steroid dose and exacerbation rate (as well as e.g.: blood eosinophils, FEV1, weight) in patients previously unresponsive to mepolizumab (with proven persistent airway eosinophilia), or in selected anti-IL5-naive patients with suspected vasculitis. Methods Maintenance prednisolone dose and exacerbation history were prospectively recorded at baseline (Bas) and at six months (6M), along with weight, blood eosinophils, lung function, Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Questionnaire (ACQ), fractional concentration of expired nitric oxide (FeNO). The data were analysed retrospectively. In view of the small number of patients descriptive statistics only are reported. Results Between January 2018 and April 2019, 17 severe asthma patients had received at least one reslizumab infusion: nine of these were anti-IL5-naive and eight had previously been unresponsive to mepolizumab. This latter group had worse AQLQ (2.6), exacerbations (4.5) and lung function (53% predicted) at baseline compared to the naive group (3.2, 1 and 59% respectively). Sixteen patients completed at least six months treatment, with the remaining patient stopping due to an adverse reaction (rash). In previous mepolizumab-failed patients, reslizumab reduced the median daily prednisolone dose from 20 to 15 mg over 6-months, and from 17.5 to 15 mg in the biologic-naive group. Summary Reslizumab appears to be an effective medication in reducing prednisolone use in patients who had failed mepolizumab, or who were considered too severe for mepolizumab at the UK licensed dose (patients with suspected of vasculitis). A larger population and for a longer duration of follow-up are needed to confirm these real-life patient findings.

PurposeTo assess the clinical utility of next-generation sequencing (NGS) for the diagnosis of patients with optic atrophy (OA).DesignRetrospective cohort study.Methods97 patients were referred to the McMaster University Medical Center (Hamilton, Ontario) for evaluation of bilateral OA. All patients were sent for NGS including a 22 nuclear gene panel and/or complete mitochondrial DNA (mtDNA) sequencing. Positive genetic test results and abnormal vibration sensation were compared in patients +/- environmental exposures or a family history.Results19/94 (20.2%) had a positive nuclear variant, of which 15/19 (78.9%) were in the OPA1 gene. No positive mtDNA variants were identified. The detection of a positive genetic variant was significantly different in patients who reported excessive ethanol use, but not in patients who smoke (0/19 (0%) vs. 19/78 (24.4%), P = 0.0164 and 4/22 (18.2%) vs. 15/74 (20.3%), P = 0.829, respectively). Patients with a positive family history were more likely to have a positive genetic variant compared to patients with a negative family history (P = 0.0112). There were significantly more excessive drinkers with an abnormal vibration sensation (P = 0.026), and with a similar trend in smokers (P = 0.074).ConclusionsAll positive genetic variants were identified in nuclear genes. We identified a potential independent pathophysiological link between a history of excessive ethanol consumption and bilateral OA. Further investigations should evaluate and identify potential environmental risk factors for OA.

Study Objectives Assess the physiologic and self-reported effects of wind turbine noise (WTN) on sleep. Methods Laboratory sleep study (n = 50 participants: n = 24 living close to wind turbines and n = 26 as a reference group) using polysomnography, electrocardiography, salivary cortisol, and questionnaire endpoints. Three consecutive nights (23:00–07:00): one habituation followed by a randomized quiet Control and an intervention night with synthesized 32 dB LAEq WTN. Noise in WTN nights simulated closed and ajar windows and low and high amplitude modulation depth. Results There was a longer rapid eye movement (REM) sleep latency (+16.8 min) and lower amount of REM sleep (−11.1 min, −2.2%) in WTN nights. Other measures of objective sleep did not differ significantly between nights, including key indicators of sleep disturbance (sleep efficiency: Control 86.6%, WTN 84.2%; wakefulness after sleep onset: Control 45.2 min, WTN 52.3 min; awakenings: Control n = 11.4, WTN n = 11.5) or the cortisol awakening response. Self-reported sleep was consistently rated as worse following WTN nights, and individuals living close to wind turbines had worse self-reported sleep in both the Control and WTN nights than the reference group. Conclusions Amplitude-modulated continuous WTN may impact on self-assessed and some aspects of physiologic sleep. Future studies are needed to generalize these findings outside of the laboratory and should include more exposure nights and further examine possible habituation or sensitization.

AIM: To identify issues and challenges of genomics education in Hong Kong, Taiwan and Mainland China. BACKGROUND: The use of genetics/genomics in health care, such as genetic testing, pharmacogenomics and tumour profiling in the context of cancer, is increasing. The rapid application of genetics/genomics in clinical practice requires healthcare providers to be competent to practise genetics-related patient care. SOURCES OF EVIDENCE: We reviewed current practices in genomics education in nursing in Hong Kong, Taiwan and Mainland China, including the opportunities for nurses to advance their knowledge and recommendations to incorporate genomics education in the nursing curriculum in these regions. FINDINGS: While many citizens and health professionals recognize the importance of new and exciting research areas of genomics/genetics, there are still many gaps in the translation of genetic/genomic medicine into clinical practice. There is also a similar lack of genetics professionals in China. CONCLUSION: Hong Kong, Taiwan and Mainland China face challenges in promoting genetic education in nursing. A strategic approach in a coordinated effort ineffectively translating genomic knowledge into healthcare practice should be established in these three regions. IMPLICATIONS FOR NURSING AND POLICY: Nursing educators in Hong Kong, Taiwan and Mainland China should link with the international nursing community (e.g. Global Genomics Nursing Alliance) and form closer networks to improve education in the area of genetics and genomics. From a policy level, genomics education is suggested to be incorporated in nursing curriculum to enhance nurses’ competency in incorporating genetics/genomics service into patient care.