Tolkien’s Sub-Creation and Secondary Worlds: Implications for a Robust Moral Psychology

In his work, “On Fairy Stories,” J. R. R. Tolkien offers a detailed account of what he calls Sub-creation, along with the corresponding notions of Primary and Secondary Worlds. In this paper, I suggest that Tolkien’s concept of Sub-creation can be creatively appropriated in the realm of moral psychology and there applied to the fundamental relationship between self and other – or in Judeo-Christian terms, “I” and my neighbor. Through appeal to Tolkien’s thought and to the wider Christian theological tradition, and in constructive tension with the contemporary psychoanalytic attention to “intersubjectivity,” I attempt to elucidate the power and appropriate function of the human imagination to dispose us to good moral action, and so to bring us closer to ultimate happiness

NUMERICAL MODELING OF THE VERTICAL HEAT TRANSPORT THROUGH THE DIFFUSIVE LAYER OF THE ARCTIC OCEAN

The Arctic Ocean has been a subject of increasing interest in recent years due to the reduction of the sea-ice thickness and spatial coverage and its implications for climate change. The future state of the Arctic is likely to be linked to vertical heat transport by microscale processes, specifically, double-diffusive convection. A series of realistic three-dimensional direct numerical simulations (DNS) were conducted to assess the vertical heat transport through thermohaline staircases in the Arctic region. Results revealed that vertical fluxes exceeded those of extant four-thirds flux laws by as much as a factor of two, and suggest that the 4/3 exponent requires downward revision. Results also showed that two-dimensional DNS can provide an accurate approximation of heat fluxes when the density ratio is sufficiently large. DNS results also reveal that the models with rigid boundaries result in heat flux estimates that are lower than those from models with periodic boundary conditions. Finally, the DNS-derived flux law was applied to Arctic data and results supported the conclusion that lab-derived flux laws significantly underestimate heat flux. All of these results suggest that vertical heat transport due to double-diffusive convection is a significant contributor to the measured reduction of Arctic sea-ice.http://archive.org/details/numericalmodelin1094532855Lieutenant Commander, United States Nav

Soluble glycoprotein VI is a predictor of major bleeding in patients with suspected heparin-induced thrombocytopenia

We have shown that patients with suspected heparin-induced thrombocytopenia (HIT) have a high incidence of major bleeding. Recent studies have implicated elevated soluble glycoprotein VI (sGPVI) levels as a potential risk factor for bleeding. We sought to determine if elevated sGPVI plasma levels are associated with major bleeding events in patients with suspected HIT. We used a cohort of 310 hospitalized adult patients with suspected HIT who had a blood sample collected at the time HIT was suspected. Plasma sGPVI levels were measured by using enzyme-linked immunosorbent assay. Patients were excluded who had received a platelet transfusion within 1 day of sample collection because of the high levels of sGPVI in platelet concentrates. We assessed the association of sGPVI (high vs low) with International Society on Thrombosis and Haemostasis major bleeding events by multivariable logistic regression, adjusting for other known risk factors for bleeding. Fifty-four patients were excluded due to recent platelet transfusion, leaving 256 patients for analysis. Eighty-nine (34.8%) patients had a major bleeding event. Median sGPVI levels were significantly elevated in patients with major bleeding events compared with those without major bleeding events (49.09 vs 31.93 ng/mL; P \u3c .001). An sGPVI level \u3e43 ng/mL was independently associated with major bleeding after adjustment for critical illness, sepsis, cardiopulmonary bypass surgery, and degree of thrombocytopenia (adjusted odds ratio, 2.81; 95% confidence interval, 1.51-5.23). Our findings suggest that sGPVI is associated with major bleeding in hospitalized patients with suspected HIT. sGPVI may be a novel biomarker to predict bleeding risk in patients with suspected HIT

Partial treatment response to capmatinib in MET-amplified metastatic intrahepatic cholangiocarcinoma: case report & review of literature

Cholangiocarcinoma is a highly morbid gastrointestinal malignancy for which available therapies are limited. Standard of care includes cytotoxic chemotherapies such as gemcitabine, platinum agents, nab-paclitaxel, and fluoropyrimidine analogues. However, tolerability of these regimens varies, and patients who do not tolerate chemotherapy have limited targeted therapies and immunotherapy options. In cholangiocarcinoma, mesenchymal-epithelial transition factor (MET) amplification may present an additional opportunity for a targeted therapeutic approach, especially considering emerging data in non-small cell lung cancer. In this case, we present a metastatic cholangiocarcinoma patient with high-level MET gene amplification for whom capmatinib, a tyrosine kinase inhibitor with activity against c-MET, provided a partial response after cessation of chemotherapy

Black, Hispanic, and White Women's Perception of Heart Disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73200/1/j.0889-7204.2007.05698.x.pd

Colon Adenocarcinoma and Birt-Hogg-Dubé Syndrome in a Young Patient: Case Report and Exploration of Pathologic Implications

Birt–Hogg–Dubé syndrome (BHD) is an autosomal dominant disorder caused by germline mutations in the folliculin gene (FLCN) that result in the functional loss of the tumor suppressor folliculin. It is classically associated with cutaneous hamartomas, pulmonary cysts with spontaneous pneumothorax, and various renal cancers. In this case, we present a patient initially diagnosed with chromophobe renal cell carcinoma and subsequently found to have colorectal cancer (CRC). The presence of two separate malignancies in a young patient with a strong family history of CRC (father and paternal grandfather) led to genetic testing, which revealed an FLCN c.1177–5_1177-3del mutation, and a diagnosis of BHD was made. Out of the more than 300 known unique mutations of the FLCN coding region, the c.1285dupC mutation on exon 11 has been the only one convincingly associated with CRC thus far. While larger cohort studies are needed to further clarify this association, we present the first patient with CRC to our knowledge with an FLCN c.1177–5_1177-3del mutation and loss of heterozygosity implicating it as an initiating factor in tumorigenesis. We further explore the studies supporting and refuting the connection between BHD and CRC and highlight the molecular signaling pathways that may play a role in pathogenesis

The Effects of Physical Activity on Cancer Patients Undergoing Treatment with Immune Checkpoint Inhibitors: A Scoping Review

Background: Cancer therapies are associated with multiple adverse effects, including (but not limited to) cancer-related fatigue (CRF). Fatigue is one of the most common side effects of immune checkpoint inhibitors (ICIs), occurring in up to 25% of patients. Physical activity has been shown to help reduce CRF through modulating the immune system, and may synergistically aid in the anti-tumor effects of ICIs. This review describes the nature and scope of evidence for the effects associated with concurrent physical activity while undergoing ICI therapy. Method: Scoping review methodology was utilized to identify studies, extract data, and collate and summarize results. Results: In literature published from January 2010 through to August 2021, only one human study and three pre-clinical studies met inclusion criteria. Conclusion: Existing evidence supports that physical activity is associated with decreased treatment-related toxicities such as CRF. However, further investigation is warranted. The dearth of clinical studies illustrates the need for more research to address this question, to guide patients and their providers in the application of appropriate physical activity interventions in those patients undergoing ICI

The Effects of Physical Activity on Cancer Patients Undergoing Treatment with Immune Checkpoint Inhibitors: A Scoping Review.

BACKGROUND: Cancer therapies are associated with multiple adverse effects, including (but not limited to) cancer-related fatigue (CRF). Fatigue is one of the most common side effects of immune checkpoint inhibitors (ICIs), occurring in up to 25% of patients. Physical activity has been shown to help reduce CRF through modulating the immune system, and may synergistically aid in the anti-tumor effects of ICIs. This review describes the nature and scope of evidence for the effects associated with concurrent physical activity while undergoing ICI therapy. METHOD: Scoping review methodology was utilized to identify studies, extract data, and collate and summarize results. RESULTS: In literature published from January 2010 through to August 2021, only one human study and three pre-clinical studies met inclusion criteria. CONCLUSION: Existing evidence supports that physical activity is associated with decreased treatment-related toxicities such as CRF. However, further investigation is warranted. The dearth of clinical studies illustrates the need for more research to address this question, to guide patients and their providers in the application of appropriate physical activity interventions in those patients undergoing ICI

Perpetrators, victims, bystanders and up standers: cyber bullying in a special school context.

This study offers a multi-dimensional analysis of ‘real world’ cyberbullying between members of a special school community. The purpose of this article is to analyse the social and educational contexts within which interactions of this nature are embedded.The interview both illuminated a number of themes pertinent to the current literature and extended those related to the call for further analysis of the contextual determinants of cyberbullying.The influence of the conditions experienced by the children involved (Attention Deficit Hyperactivity Disorder (ADHD) and Autistic Spectrum Condition (ASC)) is discussed and demonstrated. This use of natural observation provides a current and ‘real world’ illustration of teacher perceptions of the complex behaviours and interactions occurring in cyberspace, which hold potential for grave consequences. A hopeful tone is maintained as the potential for selfless upstander behaviour and resolution via the involvement of supportive and knowledgeable pastoral staff is realised in the article’s conclusion.<br/

Duration of Purkinje cell complex spikes increases with their firing frequency

Climbing fiber (CF) triggered complex spikes (CS) are massive depolarization bursts in the cerebellar Purkinje cell (PC), showing several high frequency spikelet components (\ub1600 Hz). Since its early observations, the CS is known to vary in shape. In this study we describe CS waveforms, extracellularly recorded in awake primates (Macaca mulatta) performing saccades. Every PC analyzed showed a range of CS shapes with profoundly different duration and number of spikelets. The initial part of the CS was rather constant but the later part differed greatly, with a pronounced jitter of the last spikelets causing a large variation in total CS duration. Waveforms did not effect the following pause duration in the simple spike (SS) train, nor were SS firing rates predictive of the waveform shapes or vice versa. The waveforms did not differ between experimental conditions nor was there a preferred sequential order of CS shapes throughout the recordings. Instead, part of their variability, the timing jitter of the CS\u2019s last spikelets, strongly correlated with interval length to the preceding CS: shorter CS intervals resulted in later appearance of the last spikelets in the CS burst, and vice versa. A similar phenomenon was observed in rat PCs recorded in vitro upon repeated extracellular stimulation of CFs at different frequencies in slice experiments. All together these results strongly suggest that the variability in the timing of the last spikelet is due to CS frequency dependent changes in PC excitability