A study of the variety of meanings given to a list of three hundred multi-meaning words by children in grades four, five and six.

Thesis (Ed.M.)--Boston Universit

Dacarbazine and its structural analogues : systematic computational studies of the configurations, tautomers, tautomerization pathways and bimolecular nucleophilic substitution reaction mechanisms of dacarbazine : a triazene containing anti-neoplastic agent, and its structural analogues

xvii, 181, [192] leaves : ill. (some col.) ; 29 cm.Includes abstract and appendix.Includes bibliographical references (leaves 172-181).A monomethyltriazene is believed to be the active metabolite of triazene containing anti-neoplastic agents and is thought to methylate the O6-oxygen of guanine to form methylguanine. Methylguanine is believed to be responsible for the observed cytotoxic properties of triazene containing anti-neoplastic agents. Dacarbazine, a triazene containing anti-neoplastic agent, has been shown to be the single most active agent for the treatment of malignant melanoma. Computational studies, including conformational and tautomer analysis, tautomerization pathways and a model mechanism of action, were conducted in the hopes that a better understanding of the chemical and physical properties of triazene containing anti-neoplastic compounds could be provided. This study found that the tautomerization of a monomethyltriazene is a relatively low energy process and the tautomer form will preferentially undergo an S N 2 type reaction. It is proposed that following demethylation DTIC would preferentially undergo tautomerization followed by an S N 2 type reaction to form methylguanine

Peer-to-peer support on Facebook for caregivers of children and youth with complex care needs in New Brunswick: An environmental scan

This environmental scan aimed to describe the purpose, use, and reach of health-related peer-to-peer support groups on Facebook for caregivers of children and youth with complex care needs in New Brunswick. A total of 3,104 searches on Facebook and consultations with thirty-two stakeholders led to the identification of forty-seven Facebook support groups (twenty-one active). Groups targeted a range of conditions, with autism and related intellectual disabilities appearing most frequently. Content analysis of posts indicated that groups were primarily used to exchange informational support. This study showed that Facebook-based peer-to-peer support groups are available to families of children and youth with complex care needs in the province. This work also lays a foundation for future scans of Facebook-based support groups in other Canadian provinces and beyond.La présente analyse du milieu visait à décrire l’objectif, l’utilisation et la portée des groupes de soutien entre pairs liés à la santé sur Facebook pour les personnes qui s’occupent d’enfants et de jeunes ayant des besoins de soins complexes au Nouveau-Brunswick. En tout, 3 104 recherches sur Facebook et des consultations auprès de 32 intervenants ont permis de repérer 47 groupes de soutien sur Facebook, dont 21 groupes actifs. Des groupes ciblaient un éventail de troubles; l’autisme et les déficiences intellectuelles connexes étaient ceux qui étaient les plus fréquents. Les analyses de contenu des messages ont révélé que les groupes étaient principalement utilisés pour échanger des informations de soutien. Selon cette étude, des groupes de soutien entre pairs sur Facebook sont offerts aux familles d’enfants et de jeunes ayant des besoins de soins complexes dans la province. De plus, ce travail jette les bases de futures analyses de groupes de soutien sur Facebook d’autres provinces canadiennes et d’ailleurs

Synaptic expression of TAR-DNA-binding protein 43 in the mouse spinal cord determined using super-resolution microscopy

Funding: This work was supported by Motor Neurone Disease (MND) Association UK (Miles/Apr18/863-791), Chief Scientist Office, RS Macdonald Charitable Trust, ALS CURE Project, the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (695568 SYNNOVATE), Simons Foundation Autism Research Initiative (529085), and the Wellcome Trust (Technology Development grant 202932).Amyotrophic Lateral Sclerosis (ALS) is characterised by a loss of motor neurons in the brain and spinal cord that is preceded by early-stage changes in synapses that may be associated with TAR-DNA-Binding Protein 43 (TDP-43) pathology. Cellular inclusions of hyperphosphorylated TDP-43 (pTDP-43) are a key hallmark of neurodegenerative diseases such ALS. However, there has been little characterisation of the synaptic expression of TDP-43 inside subpopulations of spinal cord synapses. This study utilises a range of high-resolution and super-resolution microscopy techniques with immunolabelling, as well as an aptamer-based TDP-43 labelling strategy visualised with single-molecule localisation microscopy, to characterise and quantify the presence of pTDP-43 in populations of excitatory synapses near where motor neurons reside in the lateral ventral horn of the mouse lumbar spinal cord. We observe that TDP-43 is expressed in approximately half of spinal cord synapses as nanoscale clusters. Synaptic TDP-43 clusters are found most abundantly at synapses associated with VGLUT1-positive presynaptic terminals, compared to VGLUT2-associated synapses. Our nanoscopy techniques showed no difference in the subsynaptic expression of pTDP-43 in the ALS mouse model, SOD1G93a, compared to healthy controls, despite prominent structural deficits in VGLUT1-associated synapses in SOD1G93a mice. This research characterizes the basic synaptic expression of TDP-43 with nanoscale precision and provides a framework with which to investigate the potential relationship between TDP-43 pathology and synaptic pathology in neurodegenerative diseases.Publisher PDFPeer reviewe

Synaptic expression of TAR-DNA-binding protein 43 in the mouse spinal cord determined using super-resolution microscopy

Amyotrophic Lateral Sclerosis (ALS) is characterised by a loss of motor neurons in the brain and spinal cord that is preceded by early-stage changes in synapses that may be associated with TAR-DNA-Binding Protein 43 (TDP-43) pathology. Cellular inclusions of hyperphosphorylated TDP-43 (pTDP-43) are a key hallmark of neurodegenerative diseases such ALS. However, there has been little characterisation of the synaptic expression of TDP-43 inside subpopulations of spinal cord synapses. This study utilises a range of high-resolution and super-resolution microscopy techniques with immunolabelling, as well as an aptamer-based TDP-43 labelling strategy visualised with single-molecule localisation microscopy, to characterise and quantify the presence of pTDP-43 in populations of excitatory synapses near where motor neurons reside in the lateral ventral horn of the mouse lumbar spinal cord. We observe that TDP-43 is expressed in approximately half of spinal cord synapses as nanoscale clusters. Synaptic TDP-43 clusters are found most abundantly at synapses associated with VGLUT1-positive presynaptic terminals, compared to VGLUT2-associated synapses. Our nanoscopy techniques showed no difference in the subsynaptic expression of pTDP-43 in the ALS mouse model, SOD1G93a, compared to healthy controls, despite prominent structural deficits in VGLUT1-associated synapses in SOD1G93a mice. This research characterises the basic synaptic expression of TDP-43 with nanoscale precision and provides a framework with which to investigate the potential relationship between TDP-43 pathology and synaptic pathology in neurodegenerative diseases

Application of tethered ruthenium catalysts to asymmetric hydrogenation of ketones, and the selective Hydrogenation of aldehydes

An improved method for the synthesis of tethered ruthenium(II) complexes of monosulfonylated diamines is described, together with their application to the hydrogenation of ketones and aldehydes. The complexes were applied directly, in their chloride form, to asymmetric ketone hydrogenation, to give products in excess of 99% ee in the best cases, using 30 bar of hydrogen at 60 °C, and to the selective reduction of aldehydes over other functional groups

Functional evolution of nuclear structure

The evolution of the nucleus, the defining feature of eukaryotic cells, was long shrouded in speculation and mystery. There is now strong evidence that nuclear pore complexes (NPCs) and nuclear membranes coevolved with the endomembrane system, and that the last eukaryotic common ancestor (LECA) had fully functional NPCs. Recent studies have identified many components of the nuclear envelope in living Opisthokonts, the eukaryotic supergroup that includes fungi and metazoan animals. These components include diverse chromatin-binding membrane proteins, and membrane proteins with adhesive lumenal domains that may have contributed to the evolution of nuclear membrane architecture. Further discoveries about the nucleoskeleton suggest that the evolution of nuclear structure was tightly coupled to genome partitioning during mitosis

Exploring the Use of a Facebook-Based Support Group for Caregivers of Children and Youth With Complex Care Needs: Qualitative Descriptive Study

BackgroundCaregivers of children and youth with complex care needs (CCN) require substantial support to ensure the well-being of their families. Web-based peer-to-peer (P2P) support groups present an opportunity for caregivers to seek and provide timely informational and emotional support. Despite the widespread use of social media for health-related support across diverse patient and caregiver populations, it is unclear how caregivers of children and youth with CCN use and potentially benefit from these groups. ObjectiveThe aim of this study is to explore the use of a web-based P2P support group for caregivers of children and youth with CCN in New Brunswick, Canada, and investigate factors related to its use by members. MethodsThe study sample consisted of individuals who joined a closed Facebook group and an analysis of content published to the group. In phase 1, a Facebook group was developed in consultation with a patient and family advisory council, and members were recruited to the group. Phase 2 of this study consisted of an observation period during which posts and related interactions (ie, likes, loves, and comments) by members were collected. In phase 3, a web-based survey was distributed, and semistructured interviews were conducted with a subsample of group members. Survey and interview data were analyzed using thematic analysis. ResultsA total of 108 caregivers joined the Facebook group between October 2020 and March 2021. There were 93 posts with 405 comments and 542 associated interactions (448/542, 82.7% likes and 94/542, 17.3% loves). Of these 93 posts, 37 (40%) were made by group members, and 56 (60%) were made by moderators. Of the 108 members, a subsample of 39 (36.1%) completed a web-based survey, and 14 (13%) participated in the interviews. Content analyses of posts by members revealed that inquiry (17/37, 46%), informational (15/37, 41%), and emotional posts (4/37, 11%) were the most common. Emotional posts received the highest number of interactions (median 24.5). In total, 5 themes emerged from the interviews related to the use of the group and mediating factors of interactions between group members: resource for information, altruistic contribution, varying level of engagement, perceived barriers to and facilitators of group activity, and moderators as contributing members. ConclusionsThese findings demonstrate that caregivers of children and youth with CCN seek geography-specific P2P support groups to meet informational and social support needs. This study contributes to the knowledge on how caregivers use Facebook groups to meet their support needs through moderate and passive engagement

Chiropractic care and research priorities for the pediatric population: a cross-sectional survey of Quebec chiropractors

Abstract Background Chiropractors commonly treat pediatric patients within their private practices. The objectives of this study were (1) to identify the treatment techniques and health advice used by Quebec chiropractors with pediatric patients; (2) to explore the research priorities of Quebec chiropractors for the pediatric population; and (3) to identify Quebec chiropractors’ training in the field of pediatric chiropractics. Methods A web-based cross-sectional survey was conducted among all licensed Quebec chiropractors (Qc, Canada). Descriptive statistics were used to analyze all quantitative variables. Results The results showed that among the 245 respondents (22.8% response rate), practitioners adapted their treatment techniques based on their patients’ age group, thus using softer techniques with younger pediatric patients and slowly gravitating toward techniques used with adults when patients reached the age of six. In terms of continuing education, chiropractors reported an average of 7.87 h of training on the subject per year, which mostly came from either Quebec’s College of Chiropractors (OCQ) (54.7%), written articles (46.9%) or seminars and conferences (43.7%). Both musculoskeletal (MSK) and viscerosomatic conditions were identified as high research priorities by the clinicians. Conclusions Quebec chiropractors adapt their treatment techniques to pediatric patients. In light of limited sources of continuing education in the field of pediatric chiropractics, practitioners mostly rely on the training provided by their provincial college and scientific publications. According to practitioners, future research priorities for pediatric care should focus on both MSK conditions and non-MSK conditions

PREDICT: a diagnostic accuracy study of a tool for predicting mortality within one year: who should have an advance healthcare directive?

Background: CARING is a screening tool developed to identify patients who have a high likelihood of death in 1 year. Aim: This study sought to validate a modified CARING tool (termed PREDICT) using a population of patients presenting to the Emergency Department. Setting/participants: In total, 1000 patients aged over 55 years who were admitted to hospital via the Emergency Department between January and June 2009 were eligible for inclusion in this study. Design: Data on the six prognostic indicators comprising PREDICT were obtained retrospectively from patient records. One-year mortality data were obtained from the State Death Registry. Weights were applied to each PREDICT criterion, and its final score ranged from 0 to 44. Receiver operator characteristic analyses and diagnostic accuracy statistics were used to assess the accuracy of PREDICT in identifying 1-year mortality. Results: The sample comprised 976 patients with a median (interquartile range) age of 71 years (62-81 years) and a 1-year mortality of 23.4%. In total, 50% had ≥1 PREDICT criteria with a 1-year mortality of 40.4%. Receiver operator characteristic analysis gave an area under the curve of 0.86 (95% confidence interval: 0.83-0.89). Using a cut-off of 13 points, PREDICT had a 95.3% (95% confidence interval: 93.6-96.6) specificity and 53.9% (95% confidence interval: 47.5-60.3) sensitivity for predicting 1-year mortality. PREDICT was simpler than the CARING criteria and identified 158 patients per 1000 admitted who could benefit from advance care planning. Conclusion: PREDICT was successfully applied to the Australian healthcare system with findings similar to the original CARING study conducted in the United States. This tool could improve end-of-life care by identifying who should have advance care planning or an advance healthcare directive