Teachers in Control of Mental Health Issues that Affect Adolescents’ Performance

Molly Kerr ’24Majors: English/Secondary Education and PsychologyFaculty Mentor: Dr. Comfort Ateh, Secondary Education Mental health issues have risen dramatically among adolescents over the last couple of years, which has negatively affected the performance in education, especially minority students of low socioeconomic status. This is mostly due to the lack of resources. In an independent course that focused on the effect of mental health on student performance, I explored how high school teachers can support students with mental health issues. I examined strategies through the lens of recognition, intervention, and consistency that schools and educators can employ in supporting students, especially minority students who lack the resources to confront mental problems

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Communities and Climate Change: Vulnerability to rising seas and more frequent flooding

Many communities and iwi in coastal and flood-prone locations face an uncertain future because of climate change, with rising sea levels and a greater frequency and magnitude of extreme weather events. We do not yet have a good understanding of how these long-term changes will affect people in these exposed locations, but we can learn from studies of the impacts of short-run natural hazards such as major floods and earthquakes. It is clear that individuals and households can suffer both directly and indirectly, and stressors even from single events can extend over years. These include significant financial impacts, loss of assets and resources, loss of access to valued places, loss of physical and mental health, and loss of identity and sense of belonging. Some individuals and groups may be more vulnerable to these impacts, while others may be more resilient. It is not yet clear who will be more vulnerable, nor what kinds of steps need to be taken to build resilience for the long term. Decision-making institutions such as councils will need to be proactive in working with exposed communities, anticipate the support that may be required, and offer equitable solutions. Iwi and community members will need to be involved in climate change adaptation processes, and to be in a position to make informed decisions about their future. Sometimes, people may already be facing financial, physical and mental stresses from impacts such as flooding and erosion, and at the same time may need to be involved in planning for a changing future. The social, cultural and psychological challenges could be immense, so response and adaptation processes need to be carefully designed and delivered, especially for the more vulnerable. Law and policy need to be adjusted to be fit-for-purpose for the new challenges of climate change, including the roles of government agencies, limiting exposure to hazards, and financing of adaptation. Knowledge gaps identified include: • understanding vulnerability and resilience in a climate change context; • how decision-making roles and responsibilities should be allocated especially in relation to more vulnerable people and communities; • the extent to which flood mitigation schemes will be effective in protecting communities under climate change conditions; • how iwi and community groups are already anticipating and responding to climate-related challenges; • how councils are and should be working proactively to reduce impacts on the more vulnerable; and • how information about climate change impacts can be more effectively communicated

Multiplex analysis of intratumoural immune infiltrate and prognosis in patients with stage II–III colorectal cancer from the SCOT and QUASAR 2 trials: A retrospective analysis

Background Tumour-infiltrating CD8+ cytotoxic T cells confer favourable prognosis in colorectal cancer. The added prognostic value of other infiltrating immune cells is unclear and so we sought to investigate their prognostic value in two large clinical trial cohorts. Methods We used multiplex immunofluorescent staining of tissue microarrays to assess the densities of CD8+, CD20+, FoxP3+, and CD68+ cells in the intraepithelial and intrastromal compartments from tumour samples of patients with stage II–III colorectal cancer from the SCOT trial (ISRCTN59757862), which examined 3 months versus 6 months of adjuvant oxaliplatin-based chemotherapy, and from the QUASAR 2 trial (ISRCTN45133151), which compared adjuvant capecitabine with or without bevacizumab. Both trials included patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0–1. Immune marker predictors were analysed by multiple regression, and the prognostic and predictive values of markers for colorectal cancer recurrence-free interval by Cox regression were assessed using the SCOT cohort for discovery and QUASAR 2 cohort for validation. Findings After exclusion of cases without tissue microarrays and with technical failures, and following quality control, we included 2340 cases from the SCOT trial and 1069 from the QUASAR 2 trial in our analysis. Univariable analysis of associations with recurrence-free interval in cases from the SCOT trial showed a strong prognostic value of intraepithelial CD8 (CD8IE) as a continuous variable (hazard ratio [HR] for 75th vs 25th percentile [75vs25] 0·73 [95% CI 0·68–0·79], p=2·5 × 10−16), and of intrastromal FoxP3 (FoxP3IS; 0·71 [0·64–0·78], p=1·5 × 10−13) but not as strongly in the epithelium (FoxP3IE; 0·89 [0·84–0·96], p=1·5 × 10−4). Associations of other markers with recurrence-free interval were moderate. CD8IE and FoxP3IS retained independent prognostic value in bivariable and multivariable analysis, and, compared with either marker alone, a composite marker including both markers (CD8IE-FoxP3IS) was superior when assessed as a continuous variable (adjusted [a]HR75 vs 25 0·70 [95% CI 0·63–0·78], p=5·1 × 10−11) and when categorised into low, intermediate, and high density groups using previously published cutpoints (aHR for intermediate vs high 1·68 [95% CI 1·29–2·20], p=1·3 × 10−4; low vs high 2·58 [1·91–3·49], p=7·9 × 10−10), with performance similar to the gold-standard Immunoscore. The prognostic value of CD8IE-FoxP3IS was confirmed in cases from the QUASAR 2 trial, both as a continuous variable (aHR75 vs 25 0·84 [95% CI 0·73–0·96], p=0·012) and as a categorical variable for low versus high density (aHR 1·80 [95% CI 1·17–2·75], p=0·0071) but not for intermediate versus high (1·30 [0·89–1·88], p=0·17). Interpretation Combined evaluation of CD8IE and FoxP3IS could help to refine risk stratification in colorectal cancer. Investigation of FoxP3IS cells as an immunotherapy target in colorectal cancer might be merited

Antibacterial resistance and their genetic location in MRSA isolated in Kuwait hospitals, 1994-2004

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) continues to be a major cause of serious infections in hospitals and in the community worldwide. In this study, MRSA isolated from patients in Kuwait hospitals were analyzed for resistance trends and the genetic location of their resistance determinants. METHODS: Between April 1994 and December 2004, 5644 MRSA isolates obtained from different clinical samples were studied for resistance to antibacterial agents according to guidelines from the National Committee for Clinical Laboratory Standards and the British Society for Antimicrobial Chemotherapy. The genetic location of their resistance determinants was determined by curing and transfer experiments. RESULTS: They were resistant to aminoglycosides, erythromycin, tetracycline, trimethoprim, fusidic acid, ciprofloxacin, chloramphenicol, rifampicin, mupirocin, cadmium acetate, mercuric chloride, propamidine isethionate and ethidium bromide but susceptible to vancomycin, teicoplanin and linezolid. The proportion of the isolates resistant to erythromycin, ciprofloxacin and fusidic acid increased during the study period. In contrast, the proportion of isolates resistant to gentamicin, tetracycline, chloramphenicol and trimethoprim declined. High-level mupirocin resistance increased rapidly from 1996 to 1999 and then declined. They contained plasmids of 1.9, 2.8, 3.0, 4.4, 27 and 38 kilobases. Genetic studies revealed that they carried plasmid-borne resistance to high-level mupirocin resistance (38 kb), chloramphenicol (2.8 – 4.4 kb), erythromycin (2.8–3.0 kb) and cadmium acetate, mercuric chloride, propamidine isethionate and ethidium bromide (27 kb) and chromosomal location for methicillin, the aminoglycosides, tetracycline, fusidic acid, ciprofloxacin and trimethoprim resistance. Thus, the 27 kb plasmids had resistance phenotypes similar to plasmids reported in MRSA isolates in South East Asia. CONCLUSION: The prevalence of resistance to erythromycin, ciprofloxacin, high-level mupirocin and fusidic acid increased whereas the proportion of isolates resistant to gentamicin, tetracycline, chloramphenicol and trimethoprim declined during the study period. They contained 27-kb plasmids encoding resistance to cadmium acetate, mercuric chloride, propamidine isethionate and ethidium bromide similar to plasmids isolated in MRSA from South East Asia. Molecular typing of these isolates will clarify their relationship to MRSA from South East Asia

Molecular Determinants of Survival Motor Neuron (SMN) Protein Cleavage by the Calcium-Activated Protease, Calpain

Spinal muscular atrophy (SMA) is a leading genetic cause of childhood mortality, caused by reduced levels of survival motor neuron (SMN) protein. SMN functions as part of a large complex in the biogenesis of small nuclear ribonucleoproteins (snRNPs). It is not clear if defects in snRNP biogenesis cause SMA or if loss of some tissue-specific function causes disease. We recently demonstrated that the SMN complex localizes to the Z-discs of skeletal and cardiac muscle sarcomeres, and that SMN is a proteolytic target of calpain. Calpains are implicated in muscle and neurodegenerative disorders, although their relationship to SMA is unclear. Using mass spectrometry, we identified two adjacent calpain cleavage sites in SMN, S192 and F193. Deletion of small motifs in the region surrounding these sites inhibited cleavage. Patient-derived SMA mutations within SMN reduced calpain cleavage. SMN(D44V), reported to impair Gemin2 binding and amino-terminal SMN association, drastically inhibited cleavage, suggesting a role for these interactions in regulating calpain cleavage. Deletion of A188, a residue mutated in SMA type I (A188S), abrogated calpain cleavage, highlighting the importance of this region. Conversely, SMA mutations that interfere with self-oligomerization of SMN, Y272C and SMNΔ7, had no effect on cleavage. Removal of the recently-identified SMN degron (Δ268-294) resulted in increased calpain sensitivity, suggesting that the C-terminus of SMN is important in dictating availability of the cleavage site. Investigation into the spatial determinants of SMN cleavage revealed that endogenous calpains can cleave cytosolic, but not nuclear, SMN. Collectively, the results provide insight into a novel aspect of the post-translation regulation of SMN

Preferences and beliefs in ingroup favoritism

Ingroup favoritism—the tendency to favor members of one’s own group over those in other groups—is well documented, but the mechanisms driving this behavior are not well understood. In particular, it is unclear to what extent ingroup favoritism is driven by preferences concerning the welfare of ingroup over outgroup members, vs. beliefs about the behavior of ingroup and outgroup members. In this review we analyze research on ingroup favoritism in economic games, identifying key gaps in the literature and providing suggestions on how future work can incorporate these insights to shed further light on when, why, and how ingroup favoritism occurs. In doing so, we demonstrate how social psychological theory and research can be integrated with findings from behavioral economics, providing new theoretical and methodological directions for future research

The evolution of lung cancer and impact of subclonal selection in TRACERx

Lung cancer is the leading cause of cancer-associated mortality worldwide. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource

The evolution of non-small cell lung cancer metastases in TRACERx

Metastatic disease is responsible for the majority of cancer-related deaths. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse