Using Developmental Frameworks to Implement Focus Groups in School-Aged Children

This poster describes the use of virtual focus groups with school-aged children in the development of a pediatric wellbeing picture scale to screen for mental health and wellbeing. Children\u27s opinions, creative ideas, and insights allow acquisition of new data and knowledge, but unfortunately, are frequently overlooked. When using developmentally-based principles, focus groups have been shown to be a successful and reliable method for collecting data from this age group and a novel way to better understand the child’s interactions and experiences. Focus groups have a number of advantages, allowing for in-depth exploration of discussion by the participants. Students in Nursing 499 conducted developmentally-based focus groups with children grades 3-5 to develop the Pediatric Well Being Picture Scale. Basing focus groups on theoretical frameworks of Piaget, Erikson, and Kohlberg creates an environment conducive to open discussion and expression of children’s ideas. These focus groups give children the opportunity to connect to one another and feel more comfortable in talking about items about emotional wellbeing. This allowed the researcher to gain an understanding of the children’s perspective for the items on the wellbeing scale. Limitations noted due to the virtual environment included maintaining the child’s attention, adequacy of technology, and assuring that each child had the opportunity to equally participate. Benefits include more openness and candor due a sense of anonymity from not being in the same location.https://orb.binghamton.edu/research_days_posters_2022/1066/thumbnail.jp

Investigating the contribution of the upper and lower lumbar spine, relative to hip motion, in everyday tasks

Background: It is commonplace for clinicians to measure range of motion (ROM) in the assessment of the lumbar spine. Traditional single 'joint' models afford measuring only a limited number of regions along the spine and may, therefore, over-simplify the description of movement. It remains to be determined if additional, useful information can be gleaned by considering the traditional 'lumbar region' as two regions. Objective: The aim of this study was to determine whether modelling the lumbar spine as two separate regions (i.e. upper and lower), yields a different understanding of spinal movement relative to hip motion, than a traditional single-joint model. This study is unique in adopting this approach to evaluate a range of everyday tasks. Method: Lumbar spine motion was measured both by being considered as a whole region (S1 to T12), and where the lumbar spine was modelled as two regions (the upper (L3-T12) and lower (S1-L3)). Results: A significant difference was evident between the relative contribution from the lower and upper spine across all movements, with the lower lumbar spine consistently contributing on average 63% of the total ROM. A significant difference was also evident between the whole lumbar spine-hip ratio, and the lower lumbar spine-hip ratio, for the movement of lifting only. The lower lumbar spine achieved greater velocity for all tasks, when compared to the upper lumbar spine. Conclusion: This study has consistently demonstrated differences in the contribution of the upper and lower spinal regions across a range of everyday tasks; hence, it would appear that greater focus should be given to performing more detailed assessments to fully appreciate spinal movement

Hot Start PCR with heat-activatable primers: a novel approach for improved PCR performance

The polymerase chain reaction (PCR) is widely used for applications which require a high level of specificity and reliability, such as genetic testing, clinical diagnostics, blood screening, forensics and biodefense. Great improvements to PCR performance have been achieved by the use of Hot Start activation strategies that aim to prevent DNA polymerase extension until more stringent, higher temperatures are reached. Herein we present a novel Hot Start activation approach in PCR where primers contain one or two thermolabile, 4-oxo-1-pentyl (OXP) phosphotriester (PTE) modification groups at 3′-terminal and 3′-penultimate internucleotide linkages. Studies demonstrated that the presence of one or more OXP PTE modifications impaired DNA polymerase primer extension at the lower temperatures that exist prior to PCR amplification. Furthermore, incubation of the OXP-modified primers at elevated temperatures was found to produce the corresponding unmodified phosphodiester (PDE) primer, which was then a suitable DNA polymerase substrate. The OXP-modified primers were tested in conventional PCR with endpoint detection, in one-step reverse transcription (RT)–PCR and in real-time PCR with SYBR Green I dye and Taqman® probe detection. When OXP-modified primers were used as substitutes for unmodified PDE primers in PCR, significant improvement was observed in the specificity and efficiency of nucleic acid target amplification

The impact of smoke exposure on the clinical phenotype of alpha-1 antitrypsin deficiency in Ireland: exploiting a national registry to understand a rare disease.

Individuals with Alpha-1 antitrypsin deficiency (AATD) have mutations in the SERPINA1 gene causing genetic susceptibility to early onset lung and liver disease that may result in premature death. Environmental interactions have a significant impact in determining the disease phenotype and outcome in AATD. The aim of this study was to assess the impact of smoke exposure on the clinical phenotype of AATD in Ireland. Clinical demographics and available thoracic computerised tomography (CT) imaging were detected from 139 PiZZ individuals identified from the Irish National AATD Registry. Clinical information was collected by questionnaire. Data was analysed to assess AATD disease severity and evaluate predictors of clinical phenotype. Questionnaires were collected from 107/139 (77%) and thoracic CT evaluation was available in 72/107 (67.2%). 74% of respondents had severe Chronic Obstructive Pulmonary Disease (COPD) (GOLD stage C or D). Cigarette smoking was the greatest predictor of impairment in FEV1 and DLCO (%predicted) and the extent of emphysema correlated most significantly with DLCO. Interestingly the rate of FEV1 decline was similar in ex-smokers when compared to never-smokers. Passive smoke exposure in childhood resulted in a greater total pack-year smoking history. Radiological evidence of bronchiectasis was a common finding and associated with increasing age. The Irish National AATD Registry facilitates clinical and basic science research of this condition in Ireland. This study illustrates the detrimental effect of smoke exposure on the clinical phenotype of AATD in Ireland and the benefit of immediate smoking cessation at any stage of lung disease

Using the Recommended Summary Plan for Emergency care and Treatment (ReSPECT) in care homes:a qualitative interview study

BACKGROUND: The Recommended Summary Plan for Emergency Care and Treatment (ReSPECT) is an advance care planning process designed to facilitate discussion and documentation of preferences for care in a medical emergency. Advance care planning is important in residential and nursing homes. AIM: To explore the views and experiences of GPs and care home staff of the role of ReSPECT in: (i) supporting, and documenting, conversations about care home residents’ preferences for emergency care situations, and (ii) supporting decision-making in clinical emergencies. SETTING/PARTICIPANTS: Sixteen GPs providing clinical care for care home residents and 11 care home staff in the West of England. METHODS: A qualitative research design using semi-structured interviews. RESULTS: Participants’ accounts described the ReSPECT process as facilitating person-centred conversations about residents’ preferences for care in emergency situations. The creation of personalised scenarios supported residents to consider their preferences. However, using ReSPECT was complex, requiring interactional work to identify and incorporate resident or relative preferences. Subsequent translation of preferences into action during emergency situations also proved difficult in some cases. Care staff played an important role in facilitating and supporting ReSPECT conversations and in translating it into action. CONCLUSIONS: The ReSPECT process in care homes was positive for GPs and care home staff. We highlight challenges with the process, communication of preferences in emergency situations and the importance of balancing detail with clarity. This study highlights the potential for a multi-disciplinary approach engaging care staff more in the process

An experimental study investigating the effect of pain relief from oral analgesia on lumbar range of motion, velocity, acceleration and movement irregularity

Background Movement alterations are often reported in individuals with back pain. However the mechanisms behind these movement alterations are not well understood. A commonly cited mechanism is pain. The aim of this study was to investigate the effect of pain reduction, from oral analgesia, on lumbar kinematics in individuals with acute and chronic low back pain. Methods A prospective, cross-sectional, experimental repeated-measures design was used. Twenty acute and 20 chronic individuals with low back pain were recruited from General Practitioner and self-referrals to therapy departments for low back pain. Participants complained of movement evoked low back pain. Inertial sensors were attached to the sacrum and lumbar spine and used to measure kinematics. Kinematic variables measured were range of motion, angular velocity and angular acceleration as well as a determining movement irregularity (a measure of deviation from smooth motion). Kinematics were investigated before and after administration of oral analgesia to instigate pain reduction. Results Pain was significantly reduced following oral analgesia. There were no significant effects on the kinematic variables before and after pain reduction from oral analgesia. There was no interaction between the variables group (acute and chronic) and time (pre and post pain reduction). Conclusion The results demonstrate that pain reduction did not alter lumbar range of motion, angular velocity, angular acceleration or movement irregularity questioning the role of pain in lumbar kinematics

Hot Start PCR with heat-activatable primers: a novel approach for improved PCR performance

The polymerase chain reaction (PCR) is widely used for applications which require a high level of specificity and reliability, such as genetic testing, clinical diagnostics, blood screening, forensics and biodefense. Great improvements to PCR performance have been achieved by the use of Hot Start activation strategies that aim to prevent DNA polymerase extension until more stringent, higher temperatures are reached. Herein we present a novel Hot Start activation approach in PCR where primers contain one or two thermolabile, 4-oxo-1-pentyl (OXP) phosphotriester (PTE) modification groups at 3′-terminal and 3′-penultimate internucleotide linkages. Studies demonstrated that the presence of one or more OXP PTE modifications impaired DNA polymerase primer extension at the lower temperatures that exist prior to PCR amplification. Furthermore, incubation of the OXP-modified primers at elevated temperatures was found to produce the corresponding unmodified phosphodiester (PDE) primer, which was then a suitable DNA polymerase substrate. The OXP-modified primers were tested in conventional PCR with endpoint detection, in one-step reverse transcription (RT)–PCR and in real-time PCR with SYBR Green I dye and Taqman® probe detection. When OXP-modified primers were used as substitutes for unmodified PDE primers in PCR, significant improvement was observed in the specificity and efficiency of nucleic acid target amplification

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery