Less is More: American Short Story Minimalism in Ernest Hemingway, Raymond Carver and Frederick Barthelme

This work suggests ways in which 'less' become 'more' in the minimalist approach of three American short story writers, Ernest Hemingway, Raymond Carver and Frederick Barthelme. By 'less', I mean minimalism's tendency to create a pared down, seemingly 'innocent' style; to use absence for effect; and to omit vital narrative details. By more, I mean the range and depth of emotional effects minimalism achieves, and the ways in which it demands the reader engage with the text. Minimalism achieves its effects because, not in spite of, its tendency towards reduction, its reliance on absence. The paring down process creates interpretative indeterminacy, by omitting apparently vital information. Hemingway may be thought of as the originator of the minimalist short story; Carver and Barthelme develop new ways to implicate the reader in the creation of the text, for example by suggesting that the reader is a voyeur, and through the use of the second person narrator. Together, minimalist writing might be reconsidered in light of the ways in which it demands reader engagement. My reader is an implied one and my choice of writers suggests ways in which the minimalist aesthetic developed; how it might be valued within literary history, and in the history of the American short story in particular. I consider Hemingway in terms of the origins of the minimalist approach in the short story, hence I offer a discussion of how his work developed within the context of literary history, as a reaction to both modernism and tradition. I conclude by suggesting that the status of minimalist writing in literary history might be reconsidered in light of a renewed understanding of how this seemingly impoverished, restrained and slight writing creates works of great richness, emotional intensity, and intellectual depth

Cerebrovascular Dysfunction is Related to Depressive Symptom Severity in Young Adults

Cerebral vasodilatory responsiveness is blunted in older adults (~70 yrs) with depressive disorders and is thought to contribute to the link between depressive symptomology and increased risk for neurocognitive (e.g., dementia) and cerebral vascular (e.g., stroke) diseases. In young adults with major depressive disorder (MDD), peripheral vascular endothelial dysfunction is present and graded in relation to the severity of depressive symptoms; however, to date, limited investigations have examined cerebral vasodilatory function in young otherwise healthy adults with MDD. PURPOSE: We tested the hypothesis that cerebral vasodilatory responsiveness to a hypercapnic stimulus would be blunted in young otherwise healthy adults with MDD compared to healthy non-depressed adults (HA). Further, we hypothesized, that the magnitude of impairment in cerebrovascular function would be related to depressive symptom severity. METHODS: Ten HA (7 women; 22±2yrs) and 10 adults with MDD (8 women; 22±2yrs; n=5 tested during a major depressive episode) participated. Depressive symptom severity was evaluated with the Patient Health History Questionnaire-9 (PHQ-9) in both HA and adults with MDD. Beat-to-beat mean arterial pressure (MAP; finger photoplethysmography), middle cerebral artery blood velocity (MCAv; transcranial Doppler ultrasound), and end-tidal carbon dioxide concentration (PETCO2; capnograph) were continuously measured during baseline (i.e., normocapnia) and rebreathing-induced hypercapnia. Cerebral vascular conductance index (CVCi=MCAv•MAP-1) was calculated at baseline and at the highest common magnitude of hypercapnia achieved by all subjects during rebreathing (∆PETCO2 = 9 Torr). RESULTS: At baseline, there were no differences in MAP or CVCi between groups (both p\u3e0.05). During hypercapnia, there were no group differences in the increase in MAP (∆3±3 HA vs. ∆4±3 mmHg MDD; p=0.78). Further, neither the hypercapnia-induced increase in MCAv (∆29±7 HA vs. ∆26±8 cm•s-1 MDD; p=0.37) nor the increase in CVCi (∆39±12 HA vs. ∆30±12 %baseline MDD; p=0.13) were different between groups. However, greater severity of depressive symptoms was negatively related to cerebral vasodilatory responsiveness (R2=0.219, p=0.04). CONCLUSION: These preliminary data suggest that cerebral vasodilatory responsiveness to hypercapnia is not impaired in young adults with MDD, despite a negative relation between depressive symptom severity and the magnitude of hypercapnia-induced cerebral vasodilation

Activation of Nrf2 signaling augments Vesicular Stomatitis Virus Oncolysis via Autophagy-Driven Suppression of Antiviral Immunity

Oncolytic viruses (OVs) offer a promising therapeutic approach to treat multiple types of cancer. In this study, we show that the manipulation of the anti-oxidant network via transcription factor Nrf2 augments vesicular stomatitis virus Δ51 (VSVΔ51) replication and sensitizes cancer cells to viral oncolysis. Activation of Nrf2 signaling by the antioxidant compound sulforaphane (SFN) leads to enhanced VSVΔ51 spread in OV-resistant cancer cells and improves the therapeutic outcome in different murine syngeneic and xenograft tumor models. Furthermore, chemoresistant A549 lung cancer cells that display a constitutive dominant hyperactivation of Nrf2 signaling are particularly vulnerable to VSVΔ51 oncolysis. Mechanistically, enhanced Nrf2 signaling stimulates viral replication in cancer cells and disrupts the type I IFN response via increased autophagy. This study reveals a previously unappreciated role for Nrf2 in the regulation of autophagy and the innate antiviral response that complements the therapeutic potential of VSV-directed oncolysis against multiple types of OV-resistant or chemoresistant cancer

Cutaneous and Muscle Reactive Hyperemia in Young Adults with Major Depressive Disorder

The reactive hyperemic vasodilatory response to a brief period of tissue ischemia provides an index of microvascular function and is an independent predictor of cardiovascular morbidity and mortality. As such, reactive hyperemia is a non-invasive technique that is commonly utilized to provide an index of vascular health in various patient groups. Major depressive disorder (MDD), a non-traditional risk factor for cardiovascular disease (CVD), has been associated with blunted reactive hyperemia, though this is not a universal finding. Further, to date, the quantification of the reactive hyperemic response in adults with MDD has been limited to the forearm muscle, assessed as Doppler ultrasound derived blood velocity in the brachial artery following a period of suprasystolic cuff occlusion. PURPOSE: Here, we sought to more comprehensively assess microvascular reactive hyperemia in otherwise healthy young adults with MDD. We tested the hypothesis that both muscle and cutaneous vasodilation would be blunted in adults with MDD compared to non-depressed young adults. METHODS: Nine healthy adults (HA; age: 22±2 yrs: body mass index: 26.5 ± 1.8 kg/m2) and ten adults with MDD (non-medicated; age: 22±2 yrs: body mass index: 22.6 ± 4.4 kg/m2) participated. Forearm reactive hyperemia was assessed as the increase in blood velocity in the brachial artery following 5-min of suprasystolic cuff occlusion (distal to the olecranon process). In a subset of adults (n=5 HA; n=4 MDD), cutaneous reactive hyperemia was concurrently assessed via laser Doppler flowmetry-derived flux (perfusion units; PU). Peak and total (area-under-the-curve; AUC) reactive hyperemia were quantified for each methodological approach. RESULTS: Neither the brachial artery Doppler ultrasound-derived peak (HA: 1020±383 vs. MDD: 950±239 s-1; p=0.65) nor the total blood flow (HA: 284±77 vs. MDD: 233±153 a.u.; p=0.41) reactive hyperemic response was different between groups. Further, there were no group differences in cutaneous reactive hyperemia (peak: 83±37 HA vs. 79±15 PU MDD, p=0.85; AUC: 8764±2273 HA vs. 8935±1439 a.u. MDD; p=0.90). CONCLUSION: These preliminary data indicate that neither the muscle nor cutaneous vasodilatory response to a brief period of tissue ischemia is blunted in young adults with MDD, suggesting preserved microvascular function

The Relation Between Cognitive Function and Cerebral Vasodilatory Reactivity in Young Adults with Major Depressive Disorder

Major depressive disorder (MDD) has been associated with an elevated risk of developing neurocognitive diseases (e.g., dementia). Although the precise neurobiological mechanisms remain incompletely understood, cerebrovascular dysfunction is thought to directly contribute, at least in part, to impairments in cognitive function. Cerebral vasodilatory reactivity to a hypercapnic stimulus is blunted in older adults with MDD compared to age-matched non-depressed adults. Further, impaired cerebral vasodilation has been linked to reduced cognitive activity in older adults with depression. However, to date, limited studies have examined the relation between cognitive function and cerebrovascular function in otherwise healthy young adults with MDD. PURPOSE: We tested the hypothesis that greater hypercapnia-induced cerebral vasodilation would be related to greater fluid cognitive ability (i.e., the capacity to process and integrate new information) in young adults with MDD. METHODS: Ten adults with MDD (non-medicated; age: 22±2 yrs: body mass index: 22.8±4.5 kg/m2; education level: all enrolled in a four-year university) participated. Cognitive function was assessed via the NIH Toolbox Cognitive Function Battery (iPad). A composite fluid cognitive ability score was derived from the specific tests within the battery that measure fluid ability [e.g., Flanker, Dimensional Change Cart Sort (DCCS)]; an age-correct standard T-score of 100 indicates ability that is average compared with national data. Beat-to-beat mean arterial pressure (MAP; finger photoplethysmography), middle cerebral artery blood velocity (MCAv; transcranial Doppler ultrasound), and end-tidal carbon dioxide concentration (PETCO2; capnograph) were continuously measured during normocapnic baseline and during rebreathing-induced hypercapnia. The hypercapnia-induced (∆PETCO2=9 mmHg) increase in cerebral vascular conductance index (∆CVCi=MCAv/MAP) was used as an index of cerebral vasodilatory reactivity. RESULTS: Hypercapnia elicited an increase in CVCi in all subjects (mean: 30±12%; range: 18-60%). The age-corrected composite fluid cognitive ability standard score was 100±15 (range: 79-119). The increase in CVCi was not related to fluid cognitive ability (slope=-0.12±0.3; r2=0.02, p=0.67). In addition, the increase in CVCi was not related to either the age-corrected standard score for the Flanker task (slope=-0.38±0.4; r2=0.12, p=0.32) or for the DCCS task (slope=0.09±0.3; r2=0.02, p=0.72), both of which specifically measure executive function. CONCLUSION: These preliminary data suggest that cerebral vasodilatory reactivity to a hypercapnic stimulus is not related to fluid cognitive function in otherwise healthy college-aged adults with MDD

A multi-institutional analysis of sternoclavicular joint coverage following osteomyelitis

BACKGROUND: Sternoclavicular joint (SCJ) osteomyelitis is a rare pathology requiring urgent intervention. Several operative approaches have been described with conflicting reports. Here, we present a multi-institutional study utilizing multiple surgical pathways for SCJ reconstruction. METHODS: A multi-institutional retrospective cohort study was conducted to identify patients who underwent surgical repair for sternoclavicular osteomyelitis between 2008 and 2019. Patients were stratified according to reconstruction approach: single-stage reconstruction with advancement flap and delayed-reconstruction with flap following initial debridement. Demographics, operative approach, type of reconstruction, and postoperative outcomes were analyzed. RESULTS: Thirty-two patients were identified. Mean patient age was 56.2±13.8 years and 68.8% were male. The average body mass index (BMI) was 30.0±8.8 kg/m2. The most common infection etiologies were intravenous drug use and bacteremia (both 25%). Fourteen patients (43.8%) underwent one-stage reconstruction and 18 (56.2%) underwent delayed twostaged reconstruction. Both single and delayed-stage groups had comparable rates of reinfection (7.1% vs. 11.1%, respectively), surgical site complications (21.4% vs. 27.8%), readmissions (7.1% vs. 16.6%), and reoperations (7.1% vs. 5.6%; all P\u3e0.05). The single-stage reconstruction group had a significantly lower BMI (26.2±5.7 kg/m2 vs. 32.9±9.1 kg/m2; P CONCLUSIONS: Both single and delayed-stage approaches are appropriate methods with comparable outcomes for reconstruction for SCJ osteomyelitis. When clinically indicated, a single-stage reconstruction approach may be preferable in order to avoid a second operation as associated with the delayed phase, and possibly shortening total hospital length of stay

Staff awareness of suicide and self-harm risk in healthcare settings: A mixed-methods systematic review

Background: Suicide risk screening in healthcare settings plays a significant role in suicide prevention. Healthcare staff who are poorly informed about self-harm and suicide risk are less likely to identify and subsequently screen at-risk individuals. This mixed-method systematic review aimed to appraise and synthesise evidence from studies that explored and promoted healthcare staff's knowledge and awareness of suicide and self-harm risk in healthcare settings. Methods: Electronic databases (CINAHL, MEDLINE, APA PsycInfo, APA PsycARTICLES, Psychology and behavioural Science Collection, ERIC, and SocINDEX), the Cochrane Library, and various grey literature databases were searched for relevant studies. The level of evidence and methodological quality of the included studies were assessed. Results: Eighteen empirical studies were included. Levels of knowledge about suicide and self-harm risk varied significantly across the reviewed studies. Face-to-face group training and educational programmes, digital or online educational programmes, and an educational poster campaign were amongst the strategies used to promote awareness of suicide and self-harm risk, with the majority marginally succeeding in doing so. Limitations: The reviewed studies were heterogeneous in terms of design, interventions, and outcome measures which made it difficult to make comparisons. The overall level of scientific evidence was classified as being relatively low. The lack of blinding and lack of a control group were amongst the limitations for experimental studies. Conclusions: Long-term, routine face-to-face group training programmes should be established to educate healthcare staff about suicide risk across all professions and in specific patient groups