An Exploration of the Goodness of Fit of Web-Based Tools for Maori: Qualitative Study Using Interviews and Focus Groups.

BACKGROUND: Indigenous communities often have poorer health outcomes and services under traditional models of care. In New Zealand, this holds true for Maori people who are tangata whenua (the indigenous people). Several barriers exist that decrease the likelihood of indigenous communities often have poorer health outcomes and poor service fit under traditional models of care, including access issues, systemic and provider racism, and a lack of culturally safe and responsive services. Web-based interventions (WBIs) have been shown to be effective in supporting mental health and well-being and can overcome some of these barriers. Despite the large number of WBIs developed, more investigation is needed to know how well WBIs fit with an indigenous worldview and how they meet the needs of indigenous communities so that a digitally based future does not drive social and health inequities. OBJECTIVE: This study aims to explore the goodness-of-fit of WBIs of Maori individuals, the indigenous people of Aotearoa/New Zealand. METHODS: We used interviews (n=3) and focus groups (n=5) with 30 Maori participants to explore their views about WBIs. Interviews were analyzed using reflexive thematic analysis by members of the research team. RESULTS: Overall, there was a perception that the design of WBIs did not align with the Maori worldview, which centers around people, relationships, spirituality, and holistic views of well-being. A total of 4 key themes and several subthemes emerged, indicating that WBIs were generally considered a poor fit for Maori. Specifically, the themes were as follows: (1) WBIs are disconnected from the core values of te ao Maori (the Maori worldview), (2) WBIs could be helpful in the right context, (3) there are significant barriers that may make it harder for Maori to use WBIs than other groups, and (4) ways to improve WBIs to help engagement with Maori. CONCLUSIONS: While WBIs are often considered a way to reduce barriers to care, they may not meet the needs of Maori when used as a stand-alone intervention. If WBIs are continued to be offered, developers and researchers need to consider how to develop WBIs that are responsive and engaging to the needs of indigenous communities rather than driving inequities. Ideally, WBIs should be developed by the people they are intended for to fit with those populations' world views.

Investigating the relationship between prenatal alcohol exposure and children's behavioural and emotional development: analysis of the Growing Up in New Zealand study.

AIMS: To examine the relationship between prenatal alcohol exposure (PAE) and children's behavioural and emotional development in a large generalizable sample of women and their children in Aotearoa New Zealand. METHODS: Using data from the Growing Up in New Zealand longitudinal cohort, we investigated the relationship between maternal PAE and behavioural and emotional development in 8-year-old children. We explored secondary outcomes including measures of language, executive function, academic achievement, and adaptive behaviour. RESULTS: We found no significant differences in the measures of behavioural and emotional development in children 8 years old based on alcohol consumption. No significant differences in behavioural and emotional development were found based on amount of PAE and when PAE occurred, despite controlling for a range of potential confounding factors, such as neighbourhood deprivation and maternal health measures. PAE was associated with significantly higher scores for parent-rated oral language indicating better oral language. In Maori mothers, PAE was significantly associated with an increased risk of higher scores on two of the Strengths and Difficulties Questionnaire subscales. CONCLUSIONS: We did not find an association between PAE and behavioural and emotional development in children aged 8 years. PAE and behavioural and emotional development are difficult to measure accurately, and the moderating variables between them are complex. Future analyses will require larger cohorts of mothers and their children using precise measures of PAE and outcomes to enable more precise estimates of association.

Bacterial surface lipoproteins mediate epithelial microinvasion by Streptococcus pneumoniae.

Streptococcus pneumoniae, a common colonizer of the upper respiratory tract, invades nasopharyngeal epithelial cells without causing disease in healthy participants of controlled human infection studies. We hypothesized that surface expression of pneumococcal lipoproteins, recognized by the innate immune receptor TLR2, mediates epithelial microinvasion. Mutation of lgt in serotype 4 (TIGR4) and serotype 6B (BHN418) pneumococcal strains abolishes the ability of the mutants to activate TLR2 signaling. Loss of lgt also led to the concomitant decrease in interferon signaling triggered by the bacterium. However, only BHN418 lgt::cm but not TIGR4 lgt::cm was significantly attenuated in epithelial adherence and microinvasion compared to their respective wild-type strains. To test the hypothesis that differential lipoprotein repertoires in TIGR4 and BHN418 lead to the intraspecies variation in epithelial microinvasion, we employed a motif-based genome analysis and identified an additional 525 a.a. lipoprotein (pneumococcal accessory lipoprotein A; palA) encoded by BHN418 that is absent in TIGR4. The gene encoding palA sits within a putative genetic island present in ~10% of global pneumococcal isolates. While palA was enriched in the carriage and otitis media pneumococcal strains, neither mutation nor overexpression of the gene encoding this lipoprotein significantly changed microinvasion patterns. In conclusion, mutation of lgt attenuates epithelial inflammatory responses during pneumococcal-epithelial interactions, with intraspecies variation in the effect on microinvasion. Differential lipoprotein repertoires encoded by the different strains do not explain these differences in microinvasion. Rather, we postulate that post-translational modifications of lipoproteins may account for the differences in microinvasion.IMPORTANCEStreptococcus pneumoniae (pneumococcus) is an important mucosal pathogen, estimated to cause over 500,000 deaths annually. Nasopharyngeal colonization is considered a necessary prerequisite for disease, yet many people are transiently and asymptomatically colonized by pneumococci without becoming unwell. It is therefore important to better understand how the colonization process is controlled at the epithelial surface. Controlled human infection studies revealed the presence of pneumococci within the epithelium of healthy volunteers (microinvasion). In this study, we focused on the regulation of epithelial microinvasion by pneumococcal lipoproteins. We found that pneumococcal lipoproteins induce epithelial inflammation but that differing lipoprotein repertoires do not significantly impact the magnitude of microinvasion. Targeting mucosal innate immunity and epithelial microinvasion alongside the induction of an adaptive immune response may be effective in preventing pneumococcal colonization and disease.

Lived experience of fetal alcohol spectrum disorder: A qualitative scoping review.

AIM: To explore the lived experiences of individuals with fetal alcohol spectrum disorder (FASD), their caregivers, and professionals working with individuals with FASD. METHOD: We conducted a scoping review using qualitative methods to explore what it is like to live with FASD from the perspective of those living with FASD, their caregivers, and stakeholders experienced in working with individuals with FASD. We searched electronic databases and grey literature for research published between 2005 and 2022. RESULTS: The 47 studies included in this scoping review show that FASD affects people's lives on a daily basis. Individuals with FASD are aware of their disability and its effects. Caregivers face daily challenges raising children with FASD and are often left unsupported by professionals. Professionals are unprepared and frustrated when supporting someone with FASD. INTERPRETATION: FASD affects individuals, caregivers, and families on a daily basis; and they require improved support and funding.

Mechanisms of antigen escape from BCMA- or GPRC5D-targeted immunotherapies in multiple myeloma.

B cell maturation antigen (BCMA) target loss is considered to be a rare event that mediates multiple myeloma (MM) resistance to anti-BCMA chimeric antigen receptor T cell (CAR T) or bispecific T cell engager (TCE) therapies. Emerging data report that downregulation of G-protein-coupled receptor family C group 5 member D (GPRC5D) protein often occurs at relapse after anti-GPRC5D CAR T therapy. To examine the tumor-intrinsic factors that promote MM antigen escape, we performed combined bulk and single-cell whole-genome sequencing and copy number variation analysis of 30 patients treated with anti-BCMA and/or anti-GPRC5D CAR T/TCE therapy. In two cases, MM relapse post-TCE/CAR T therapy was driven by BCMA-negative clones harboring focal biallelic deletions at the TNFRSF17 locus at relapse or by selective expansion of pre-existing subclones with biallelic TNFRSF17 loss. In another five cases of relapse, newly detected, nontruncating, missense mutations or in-frame deletions in the extracellular domain of BCMA negated the efficacies of anti-BCMA TCE therapies, despite detectable surface BCMA protein expression. In the present study, we also report four cases of MM relapse with biallelic mutations of GPRC5D after anti-GPRC5D TCE therapy, including two cases with convergent evolution where multiple subclones lost GPRC5D through somatic events. Immunoselection of BCMA- or GPRC5D-negative or mutant clones is an important tumor-intrinsic driver of relapse post-targeted therapies. Mutational events on BCMA confer distinct sensitivities toward different anti-BCMA therapies, underscoring the importance of considering the tumor antigen landscape for optimal design and selection of targeted immunotherapies in MM.

Claw Toe Deformity After Revision Hip Arthroscopy with Concomitant Periacetabular Osteotomy: A Case Report.

CASE: A 22-year-old woman underwent revision right hip arthroscopy (HA) with concomitant periacetabular osteotomy (PAO). The total procedure time was 5.5 hours. After completion of the 3 hour HA portion, the traction boots were loosened. Eleven weeks postoperatively, she developed a left claw toe deformity. After failed conservative management, she underwent lengthening of the left flexor hallucis longus and flexor digitorum longus tendons. CONCLUSION: This is a case of a claw toe deformity after revision right HA with concomitant PAO. The possibility of this complication should be considered in cases with prolonged intraoperative times because of the use of traction boots.

EEG-based BCI Dataset of Semantic Concepts for Imagination and Perception Tasks.

Electroencephalography (EEG) is a widely-used neuroimaging technique in Brain Computer Interfaces (BCIs) due to its non-invasive nature, accessibility and high temporal resolution. A range of input representations has been explored for BCIs. The same semantic meaning can be conveyed in different representations, such as visual (orthographic and pictorial) and auditory (spoken words). These stimuli representations can be either imagined or perceived by the BCI user. In particular, there is a scarcity of existing open source EEG datasets for imagined visual content, and to our knowledge there are no open source EEG datasets for semantics captured through multiple sensory modalities for both perceived and imagined content. Here we present an open source multisensory imagination and perception dataset, with twelve participants, acquired with a 124 EEG channel system. The aim is for the dataset to be open for purposes such as BCI related decoding and for better understanding the neural mechanisms behind perception, imagination and across the sensory modalities when the semantic category is held constant.

Bimodal electroencephalography-functional magnetic resonance imaging dataset for inner-speech recognition.

The recognition of inner speech, which could give a 'voice' to patients that have no ability to speak or move, is a challenge for brain-computer interfaces (BCIs). A shortcoming of the available datasets is that they do not combine modalities to increase the performance of inner speech recognition. Multimodal datasets of brain data enable the fusion of neuroimaging modalities with complimentary properties, such as the high spatial resolution of functional magnetic resonance imaging (fMRI) and the temporal resolution of electroencephalography (EEG), and therefore are promising for decoding inner speech. This paper presents the first publicly available bimodal dataset containing EEG and fMRI data acquired nonsimultaneously during inner-speech production. Data were obtained from four healthy, right-handed participants during an inner-speech task with words in either a social or numerical category. Each of the 8-word stimuli were assessed with 40 trials, resulting in 320 trials in each modality for each participant. The aim of this work is to provide a publicly available bimodal dataset on inner speech, contributing towards speech prostheses.

Knowledge, attitudes, and practices towards fetal alcohol spectrum disorder in the New Zealand social and community sector: An online survey.

Background: Fetal Alcohol Spectrum Disorder (FASD) is a common neurodevelopmental disorder but may be underrecognized and misunderstood by people who provide health and social support services. The aim of the research is to understand the FASD knowledge, attitudes, and practices among people employed by the social and community sector in New Zealand. Methods: We conducted an online survey of people working in the New Zealand social and community sector (i.e., social workers, support workers). The survey focused on the following areas: awareness of FASD; knowledge and beliefs about FASD; the impact of FASD on professional practice; and training needs. Results: Most participants reported a basic understanding of FASD, however only 5% felt very well prepared to support someone with FASD. A large majority of participants believed that FASD diagnosis may be stigmatising for individuals or families. Conclusion: There is a need to improve training, professional development, and workplace support for social and community workers in New Zealand to support people with FASD.

Will they or won't they? Understanding New Zealand adults' attitudes towards using digital interventions.

Background: Digital interventions deliver healthcare via the internet or smartphone application to support people's well-being and health. Yet uptake is relatively poor. Furthermore, several studies exploring attitudes towards digital interventions have found inconsistent attitudes. In addition to this, regional and cultural nuances may further influence attitudes to digital interventions. Objective: This study aimed to understand New Zealand adults' attitudes towards digital interventions and their influences. Results: A mixed-method design consisting of a cross-sectional survey and semi-structured interviews found that New Zealand adults hold varied and complex attitudes towards digital interventions. Attitudes were found to be influenced by group membership and the scenarios in which digital interventions are made available. In addition, beliefs about the benefits and concerns surrounding digital interventions, knowledge, perceived views of others, and previous experience and confidence influenced these attitudes. Conclusions: Findings indicated that digital interventions would be acceptable if offered as part of the healthcare service rather than a standalone intervention. Key modifiable factors that could positively influence attitudes were identified and could be leveraged to increase the perceived acceptability of digital interventions.

Computer Navigation vs. Conventional Overlay Methods in Direct Anterior Total Hip Arthroplasty: A Single Surgeon Experience.

BACKGROUND:  The use of computer navigation (CN) is expanding in direct anterior (DA) total hip arthroplasty (THA). In this study, we investigated the use of a noninvasive, fluoroscopic-based, CN technology suite on operative outcomes in a single surgeon DA THA practice. HYPOTHESIS: Computer-navigated DA THA decreases leg length discrepancy (LLD) variation and fluoroscopic radiation dose without adding operative time compared to the traditional overlay (OL) technique. METHODS: A retrospective review was performed on a total of 109 primary DA THA patients, with 58 in the CN and 51 in the OL group. Outcome metrics were postoperative LLD, radiation dose per case, and operative time. Statistical analysis was completed with Mann-Whitney U tests for differences between the means for LLD, radiation dose, and operative time. RESULTS: No difference was observed in postoperative LLD between the CN (average: 1.8 mm) and OL (average: 1.9 mm) groups (p = 0.458). A significant reduction in average radiation dose (mGy) per case within the CN group (8.17 ± 6.09 mGy) compared to the OL group (13.17 ± 7.75 mGy) (p < 0.02) was observed. The average operative time in the CN group was 80 ± 18 minutes compared to 120 ± 32 minutes in the OL group (p < 0.01). CONCLUSION: There was no difference in LLD between the two groups. The addition of CN into a DA THA practice decreased both average radiation dose and operative time when compared to the standard OL technique.

Impact of prenatal alcohol exposure on neurodevelopmental outcomes: a systematic review.

Background: Prenatal exposure to alcohol (PAE) represents a significant public health concern. Previous research linking PAE to neurodevelopmental outcomes has been mixed and often has limited focus on residual confounding or moderating factors. Methods: A systematic review of prospective cohort studies (n = >1000) assessing the impact of PAE on neurodevelopmental outcomes was undertaken (neurophysiology, motor skills, cognition, language, academic achievement, memory, attention, executive function, affect regulation, and adaptive behaviour, social skills, or communication). Electronic searches of EMBASE, Medline, CINAHL, and Psychinfo were conducted in May 2021. A quality assessment was conducted using an adapted version of the Newcastle-Ottawa Scale (NOS). Results: Thirty longitudinal cohort studies met the inclusion criteria. Evidence of the impact of PAE was mixed across domains. We found no evidence that PAE affects executive function, but there were impacts on motor skills, cognition, language, academic achievement, attention, affect regulation, and adaptive behaviour. The most consistent adverse effect was on affect regulation (nine out of thirteen studies, six of which found an association between heavy alcohol consumption or binge drinking during pregnancy). We found no protective factors. Few studies controlled for variables in the postnatal environment. Discussion: This review was unable to conclude a safe level of alcohol consumption during pregnancy. Methodological improvements are needed to improve the quality and consistency in which PAE is studied. Further research into residual confounding variables is vital, including a greater focus on the postpartum environment.

Outcomes of distal biceps tendon repair using a dual incision, cortical button technique: a single surgeon study.

BACKGROUND: The purpose of this study was to evaluate patient-reported outcomes, function, complication rates, and radiographs in a series of patients with distal biceps tendon repair using the dual incision cortical button technique by a single surgeon. By having a single surgeon perform the surgery, the technique is standardized to all patients. Twenty-two patients consented to participate in the study. The average time from surgery to review was 2.2 years. Patient satisfaction was assessed using the DASH, Oxford, and Mayo Elbow Performance Scores. METHODS: Range of movement was assessed and compared to the unaffected limb using a goniometer. Isometric flexion and supination strength was tested using a standardized dynamometer-both measurements taken by a single physiotherapist. Radiographs were discussed at the time of the review by 2 orthopedic surgeons to check for heterotopic ossification. RESULTS: The mean DASH score was 6.3 postsurgery at the time of follow-up. There was no significant difference in active range of movement between the repaired and nonrepaired arm in flexion, extension, supination, or pronation. Four radiographs showed evidence of heterotopic ossification (HTO)-none showed synostosis. For patients with HTO, there was evidence that supination was inhibited compared to those patients who did not have HTO. CONCLUSION: Our study found that at an average of 2 years of follow-up these patients had good outcomes clinically with no major complications. HTO was present in only 4 patients, and there was a significant difference in supination compared to those who did not have HTO. These patients had an average DASH of 14 compared to a score of 4.5 in those who did not have an HTO. The study showed that the dual incision cortical button repair remains a procedure with excellent patient outcomes at the risk of HTO.

The Effect of a Single Bout of Continuous Aerobic Exercise on Glucose, Insulin and Glucagon Concentrations Compared to Resting Conditions in Healthy Adults: A Systematic Review, Meta-Analysis and Meta-Regression.

BACKGROUND: Elevated glucose and insulin levels are major risk factors in the development of cardiometabolic disease. Aerobic exercise is widely recommended to improve glycaemic control, yet its acute effect on glycaemia and glucoregulatory hormones has not been systematically reviewed and analysed in healthy adults. OBJECTIVE: To determine the effect of a single bout of continuous aerobic exercise on circulating glucose, insulin, and glucagon concentrations in healthy adults. METHODS: CENTRAL, CINAHL, Embase, Global Health, HMIC, Medline, PubMed, PsycINFO, ScienceDirect, Scopus and Web of Science databases were searched from inception to May 2020. Papers were included if they reported a randomised, crossover study measuring glucose and/or insulin and/or glucagon concentrations before and immediately after a single bout of continuous aerobic exercise (≥ 30 min) compared to a time-matched, resting control arm in healthy adults. The risk of bias and quality of evidence were assessed using the Cochrane Risk of Bias Tool and GRADE approach, respectively. Random-effects meta-analyses were performed for glucose, insulin, and glucagon. Sub-group meta-analyses and meta-regression were performed for categorical (metabolic state [postprandial or fasted], exercise mode [cycle ergometer or treadmill]) and continuous (age, body mass index, % males, maximal aerobic capacity, exercise duration, exercise intensity) covariates, respectively. RESULTS: 42 papers (51 studies) were considered eligible: glucose (45 studies, 391 participants), insulin (38 studies, 377 participants) and glucagon (5 studies, 47 participants). Acute aerobic exercise had no significant effect on glucose concentrations (mean difference: - 0.05 mmol/L; 95% CI, - 0.22 to 0.13 mmol/L; P = 0.589; I2: 91.08%, large heterogeneity; moderate-quality evidence). Acute aerobic exercise significantly decreased insulin concentrations (mean difference: - 18.07 pmol/L; 95% CI, - 30.47 to - 5.66 pmol/L; P = 0.004; I2: 95.39%, large heterogeneity; moderate-quality evidence) and significantly increased glucagon concentrations (mean difference: 24.60 ng/L; 95% CI, 16.25 to 32.95 ng/L; P < 0.001; I2: 79.36%, large heterogeneity; moderate-quality evidence). Sub-group meta-analyses identified that metabolic state modified glucose and insulin responses, in which aerobic exercise significantly decreased glucose (mean difference: - 0.27 mmol/L; 95% CI, - 0.55 to - 0.00 mmol/L; P = 0.049; I2: 89.72%, large heterogeneity) and insulin (mean difference: - 42.63 pmol/L; 95% CI, - 66.18 to - 19.09 pmol/L; P < 0.001; I2: 81.29%, large heterogeneity) concentrations in the postprandial but not fasted state. Meta-regression revealed that the glucose concentrations were also moderated by exercise duration and maximal aerobic capacity. CONCLUSIONS: Acute aerobic exercise performed in the postprandial state decreases glucose and insulin concentrations in healthy adults. Acute aerobic exercise also increases glucagon concentrations irrespective of metabolic state. Therefore, aerobic exercise undertaken in the postprandial state is an effective strategy to improve acute glycaemic control in healthy adults, supporting the role of aerobic exercise in reducing cardiometabolic disease incidence. PROSPERO REGISTRATION NUMBER: CRD42020191345.

A Novel Radiographic Finding of Intracapsular Heterotopic Ossification: A Report of Two Cases.

Symptomatic heterotopic ossification (HO) is a complication of hip arthroscopy that occurs in less than 1% of cases. To our knowledge, there are no reported cases of symptomatic intracapsular HO. We present 2 patients with a radiographic finding associated with intracapsular HO. Both patients underwent revision hip arthroscopy and required capsular reconstruction due to void of the iliofemoral ligament following excision of HO. We believe this radiographic finding may be useful to hip preservationists as it may be associated with capsular deficiency necessitating capsular reconstruction upon revision hip arthroscopy.

Combined CCNE1 high-level amplification and overexpression is associated with unfavourable outcome in tubo-ovarian high-grade serous carcinoma.

CCNE1 amplification is a recurrent alteration associated with unfavourable outcome in tubo-ovarian high-grade serous carcinoma (HGSC). We aimed to investigate whether immunohistochemistry (IHC) can be used to identify CCNE1 amplification status and to validate whether CCNE1 high-level amplification and overexpression are prognostic in HGSC. A testing set of 528 HGSC samples stained with two optimised IHC assays (clones EP126 and HE12) was subjected to digital image analysis and visual scoring. DNA and RNA chromogenic in situ hybridisation for CCNE1 were performed. IHC cut-off was determined by receiver operating characteristics (ROC). Survival analyses (endpoint ovarian cancer specific survival) were performed and validated in an independent validation set of 764 HGSC. Finally, combined amplification/expression status was evaluated in cases with complete data (n = 1114). CCNE1 high-level amplification was present in 11.2% of patients in the testing set and 10.2% in the combined cohort. The optimal cut-off for IHC to predict CCNE1 high-level amplification was 60% positive tumour cells with at least 5% strong staining cells (sensitivity 81.6%, specificity 77.4%). CCNE1 high-level amplification and overexpression were associated with survival in the testing and validation set. Combined CCNE1 high-level amplification and overexpression was present in 8.3% of patients, mutually exclusive to germline BRCA1/2 mutation and significantly associated with a higher risk of death in multivariate analysis adjusted for age, stage and cohort (hazard ratio = 1.78, 95 CI% 1.38-2.26, p < 0.0001). CCNE1 high-level amplification combined with overexpression identifies patients with a sufficiently poor prognosis that treatment alternatives are urgently needed. Given that this combination is mutually exclusive to BRCA1/2 germline mutations, a predictive marker for PARP inhibition, CCNE1 high-level amplification combined with overexpression may serve as a negative predictive test for sensitivity to PARP inhibitors.

Pelvic occupation: the challenges of treating a symptomatic tarlov cyst.

Tarlov (perineural) cysts are meningeal dilations of the posterior spinal nerve root sheath located in between the peri- and endoneurium. We present a patient with a symptomatic sacral Tarlov cyst and the technical challenges faced by surgically treating the lesion by disconnection of the cyst from the subarachnoid space.

Environmental Public Health Tracking Program Advances and Successes: Highlights From the First 15 Years.

Over the past 15 years, the National Environmental Public Health Tracking Program (Tracking Program) has advanced technologically and programmatically, evolving from an abstract concept to a mature program. The Tracking Program, in collaboration with national, state, and local partners, uses data and expertise to identify and address environmental public health needs and improve public health capacity across the United States. Examples of the successful application of environmental public health tracking include informing health impact assessments and filling data gaps. The Tracking Program plans to continue working to direct innovative programs and solutions that protect and improve community health in years to come. With support from the Tracking Program, health departments can enhance their abilities to plan and conduct environmental public health activities.