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Snow is an important driver of ecosystem processes in cold biomes. Snow accumulation determines ground temperature, light conditions, and moisture availability during winter. It also affects the growing season’s start and end, and plant access to moisture and nutrients. Here, we review the current knowledge of the snow cover’s role for vegetation, plant-animal interactions, permafrost conditions, microbial processes, and biogeochemical cycling. We also compare studies of natural snow gradients with snow experimental manipulation studies to assess time scale difference of these approaches. The number of tundra snow studies has increased considerably in recent years, yet we still lack a comprehensive overview of how altered snow conditions will affect these ecosystems. Specifically, we found a mismatch in the timing of snowmelt when comparing studies of natural snow gradients with snow manipulations. We found that snowmelt timing achieved by snow addition and snow removal manipulations (average 7.9 days advance and 5.5 days delay, respectively) were substantially lower than the temporal variation over natural spatial gradients within a given year (mean range 56 days) or among years (mean range 32 days). Differences between snow study approaches need to be accounted for when projecting snow dynamics and their impact on ecosystems in future climates.

We generalize the shuffle theorem and its $(km,kn)$ version, as conjectured by Haglund et al. and Bergeron et al. and proven by Carlsson and Mellit, and Mellit, respectively. In our version the $(km,kn)$ Dyck paths on the combinatorial side are replaced by lattice paths lying under a line segment whose x and y intercepts need not be integers, and the algebraic side is given either by a Schiffmann algebra operator formula or an equivalent explicit raising operator formula. We derive our combinatorial identity as the polynomial truncation of an identity of infinite series of $\operatorname {\mathrm {GL}}_{l}$ characters, expressed in terms of infinite series versions of LLT polynomials. The series identity in question follows from a Cauchy identity for nonsymmetric Hall–Littlewood polynomials.

We prove the extended delta conjecture of Haglund, Remmel and Wilson, a combinatorial formula for $\Delta _{h_l}\Delta ' _{e_k} e_{n}$ , where $\Delta ' _{e_k}$ and $\Delta _{h_l}$ are Macdonald eigenoperators and $e_n$ is an elementary symmetric function. We actually prove a stronger identity of infinite series of $\operatorname {\mathrm {GL}}_m$ characters expressed in terms of LLT series. This is achieved through new results in the theory of the Schiffmann algebra and its action on the algebra of symmetric functions.

Abstract Background Chemotherapy regimens that include the utilization of gemcitabine are the standard of care in pancreatic cancer patients. However, most patients with advanced pancreatic cancer die within the first 2 years after diagnosis, even when treated with standard of care chemotherapy. This study aims to explore combination therapies that could boost the efficacy of standard of care regimens in pancreatic cancer patients. Methods In this study, we used PV-10, a 10% solution of rose bengal, to induce the death of human pancreatic tumor cells in vitro. Murine in vivo studies were carried out to examine the effectiveness of the direct injection of PV-10 into syngeneic pancreatic tumors in causing lesion-specific ablation. Intralesional PV-10 treatment was combined with systemic gemcitabine treatment in tumor-bearing mice to investigate the control of growth among treated tumors and distal uninjected tumors. The involvement of the immune-mediated clearance of tumors was examined in immunogenic tumor models that express ovalbumin (OVA). Results In this study, we demonstrate that the injection of PV-10 into mouse pancreatic tumors caused lesion-specific ablation. We show that the combination of intralesional PV-10 with the systemic administration of gemcitabine caused lesion-specific ablation and delayed the growth of distal uninjected tumors. We observed that this treatment strategy was markedly more successful in immunogenic tumors that express the neoantigen OVA, suggesting that the combination therapy enhanced the immune clearance of tumors. Moreover, the regression of tumors in mice that received PV-10 in combination with gemcitabine was associated with the depletion of splenic CD11b+Gr-1+ cells and increases in damage associated molecular patterns HMGB1, S100A8, and IL-1α. Conclusions These results demonstrate that intralesional therapy with PV-10 in combination with gemcitabine can enhance anti-tumor activity against pancreatic tumors and raises the potential for this strategy to be used for the treatment of patients with pancreatic cancer.

Rationale & Objective: Thrice-weekly hemodialysis can result in adequate urea clearance; however, the morbidity and mortality rates of patients treated with maintenance dialysis remain unacceptably high, partly because of nonadherence. African Americans have a higher prevalence of kidney failure treated with dialysis, greater dialysis nonadherence, and higher odds of hospitalization. We hypothesized that more precise ways of assessing dialysis treatment adherence will reflect the severity of nonadherence, distinguish patterns of nonadherence, and inform the design of personalized behavioral interventions. Study Design: Retrospective cohort study. Setting & Participants: African American patients receiving hemodialysis for >90 days. Exposure: Hemodialysis. Outcome: Dialysis adherence. Analytical Approach: Dialysis attendance data were displayed using a dot plot, categorized based on missed and shortened treatments, and examined for patterns. Descriptive characteristics were reported. In an exploratory analysis, associations between dialysis treatment adherence and participant characteristics were evaluated using ordinary least squares regression. An analysis was performed using missed minutes of dialysis and current metrics for measuring dialysis treatment adherence (ie, missed and shortened treatments). Results: Among 113 African American patients treated with dialysis, 47% were men; the median age was 57 years (interquartile range, 46-70 years), and the median dialysis vintage was 54 months (interquartile range, 22-90 months). With rows ordered based on the total missed minutes of dialysis, the dot plot displayed a decreasing gradient in the severity of nonadherence, with novel dialysis treatment adherence categories termed as follows: consistent underdialysis, inconsistent dialysis, and consistent dialysis. Distinct patterns of nonadherence and heterogeneity emerged within these categories. Older age was consistently associated with better adherence, as determined by the analyses performed using the total missed minutes of dialysis as well as missed and shortened treatments. Limitations: The study findings, although replicable and paradigm-shifting, might be limited by the short timeline, focus on adherence data specific to African American patients treated with dialysis, and restriction to dialysis units affiliated with 1 academic center. Conclusions: This study presents more precise and novel ways of measuring and displaying dialysis treatment adherence. The findings introduce a more personalized approach for evaluating actual dialysis uptake. Identification of unique patterns of adherence behavior is important to inform the design of effective behavioral interventions and improve outcomes for vulnerable African American patients treated with dialysis.

Abstract Aim Diabetes has been identified as a risk factor for poor outcomes in patients with COVID‐19. We examined the association of hyperglycaemia, both in the presence and absence of pre‐existing diabetes, with severity and outcomes in COVID‐19 patients. Methods Data from 74,148 COVID‐19‐positive inpatients with at least one recorded glucose measurement during their inpatient episode were analysed for presence of pre‐existing diabetes diagnosis and any glucose values in the hyperglycaemic range (>180 mg/dl). Results Among patients with and without a pre‐existing diabetes diagnosis on admission, mortality was substantially higher in the presence of high glucose measurements versus all measurements in the normal range (70–180 mg/dl) in both groups (non‐diabetics: 21.7% vs. 3.3%; diabetics 14.4% vs. 4.3%). When adjusting for patient age, BMI, severity on admission and oxygen saturation on admission, this increased risk of mortality persisted and varied by diabetes diagnosis. Among patients with a pre‐existing diabetes diagnosis, any hyperglycaemic value during the episode was associated with a substantial increase in the odds of mortality (OR: 1.77, 95% CI: 1.52–2.07); among patients without a pre‐existing diabetes diagnosis, this risk nearly doubled (OR: 3.07, 95% CI: 2.79–3.37). Conclusion This retrospective analysis identified hyperglycaemia in COVID‐19 patients as an independent risk factor for mortality after adjusting for the presence of diabetes and other known risk factors. This indicates that the extent of glucose control could serve as a mechanism for modifying the risk of COVID‐19 morality in the inpatient environment.

Abstract Introduction The Southern Community Cohort Study is a prospective study of low socioeconomic status (SES) blacks and whites from the southeastern US, where the burden of end-stage renal disease (ESRD) and its risk factors are high. We tested whether the 2.4-fold elevated risk of ESRD we previously observed in blacks compared to whites was explained by differences in baseline kidney function. Methods We conducted a case-cohort study of incident ESRD cases (n = 737) with stored blood and a probability sampled subcohort (n = 4238) and calculated estimated glomerular filtration rate (eGFR) from serum creatinine. 86% of participants were enrolled from community health centers in medically underserved areas and 14% from the general population in 12 states in the southeastern United States. Incident ESRD after entry into the cohort was ascertained by linkage of the cohort with the US Renal Data System (USRDS). Results Median (25th, 75th percentile) eGFR at baseline was 63.3 (36.0, 98.2) ml/min/1.73m2 for ESRD cases and 103.2 (86.0, 117.9) for subcohort. Black ESRD cases had higher median (25th, 75th) eGFR [63.3 (35.9, 95.9)] compared to whites [59.1 (39.4, 99.2)]. In multivariable Cox models accounting for sampling weights, baseline eGFR was a strong predictor of ESRD risk, and an interaction with race was detected (P = 0.029). The higher ESRD risk among blacks relative to whites persisted (hazard ratio: 2.58; 95% confidence interval: 1.65, 4.03) after adjustment for eGFR. Conclusion In this predominantly lower SES cohort, the racial disparity in ESRD risk is not explained by differences in baseline kidney function.

Introduction: High dietary acid load and metabolic acidosis are associated with an accelerated decline in kidney function and may contribute to the observed heterogeneity in end-stage renal disease (ESRD) risk according to APOL1 genotype. Our objective was to examine the associations of metabolic acidosis and dietary acid load with kidney disease progression, according to APOL1 genotype, among individuals with chronic kidney disease (CKD). Methods: We studied 1048 African American participants in the Chronic Renal Insufficiency Cohort. Metabolic acidosis was defined as blood levels of serum bicarbonate less than 22 mEq/L, and dietary acid load was quantified by potential renal acid load (PRAL) using data from the Diet Health Questionnaire. APOL1 status was defined as having 2 risk variants, consisting of either possible combination of the G1 and G2 risk alleles. We tested associations of APOL1 and dietary and metabolic acidosis with CKD progression, defined as time to ESRD or 50% decline in eGFR. Results: During a median follow-up period of 7 years, 379 participants had an incident CKD progression event (6.4 events per 100 person-years). After full adjustment, among participants with 2 APOL1 variants, the analysis failed to detect an association between metabolic acidosis or dietary acid load and CKD progression (hazard ratio [HR], 1.03; 95% confidence interval [CI], 0.96–1.11 per 1 mEq/L higher serum bicarbonate and an HR, 1.03; 95% CI, 0.92–1.15 per 10 mEq/L higher PRAL). Similar associations were noted among participants without the APOL1 high-risk genotype. Conclusion: In a population at high risk of developing ESRD, metabolic acidosis and dietary acid load were not associated with CKD progression. Keywords: acidosis, APOL1, chronic kidney disease, dietary acid load, end-stage renal disease

Background The therapeutic armamentarium of bladder cancer has been recently enriched with the introduction of new therapies including immune checkpoint inhibitors, receptor tyrosine kinase inhibitors and antibody drug conjugates, however treatment responses and duration of responses are still less than expected. Adoptive cellular therapy (ACT) using tumor-infiltrating lymphocytes (TILs) has potential to treat bladder cancer, as previously demonstrated by successful expansion of tumor reactive T cells from human bladder tumors.Methods A model system using OT-I T cells and an ovalbumin expressing MB49 tumor cell line (MB49OVA) was developed to study ACT in bladder cancer. Systemic ACT-treated mice were given T cells intravenously after lymphodepleting chemotherapy and followed by interleukin (IL)-2 administration. Intravesical ACT treated mice were given T cells directly into the bladder, without chemotherapy or IL-2. TILs were isolated from MB49 orthotopic tumors and expanded ex vivo in IL-2. Immune cell infiltrates were analyzed by flow cytometry. T cell infiltration was studied using a CXCR3 blocking antibody.Results Systemic ACT-treated mice had a decrease in tumor growth, increase in T cell infiltration and long-term immune protection compared with control-treated mice. OT-I T cells delivered intravesically were able to control tumor growth without lymphodepleting chemotherapy or IL-2 in MB49OVA orthotopic tumors. Intravesical delivery of TIL expanded from MB49 tumors was also able to decrease tumor growth in mice with MB49 orthotopic tumors. Blocking CXCR3 on OT-I T cells prior to intravesical delivery decreased T cell infiltration into the tumor and prevented the control of tumor growth.Conclusions This study demonstrates how TIL therapy can be used in treating different stages of bladder cancer.

The problem of computing products of Schubert classes in the cohomology ring can be formulated as theproblem of expanding skew Schur polynomial into the basis of ordinary Schur polynomials. We reformulate theproblem of computing the structure constants of the Grothendieck ring of a Grassmannian variety with respect to itsbasis of Schubert structure sheaves in a similar way; we address the problem of expanding the generating functions forskew reverse-plane partitions into the basis of polynomials which are Hall-dual to stable Grothendieck polynomials. From this point of view, we produce a chain of bijections leading to Buch’s K-theoretic Littlewood-Richardson rule.

After policy change, educational programming has been cited as one of the most powerful tools for improving food systems and decreasing food waste. University students represent a population in which emerging habits, skills, and identity may be targeted easily and changed through on-campus educational programming. To understand how to best implement programming on impacts of food, food waste, and related issues, the factors that underlie students’ behaviors related to food waste must be understood. We analyzed factors that influence food waste–related behaviors within a university student population to understand the potential for improving targeted, school-based food waste diversion programming. Four hundred and ninety-five students were surveyed to: (1) identify self-reported knowledge, attitudes, and behaviors related to food waste; (2) explore underlying factors driving food waste–related behaviors through exploratory factor analysis (EFA); and (3) understand the interactions between factors within a regression framework. Participants reported that they most often left food on their plate because it did not taste good or they had overestimated portion size. A majority of participants already performed many food waste reduction behaviors, and were both interested in taking action and aware that their efforts could make a difference. Food management skills, compost attitudes, sustainability attitudes, and reported household food waste were correlated, in various ways, with both intent to reduce and reported food waste reduction behaviors. Opportunities for improving university-related food waste programming through this data are explored.

Because depression is a major source of the global burden of illness-related disability, developing effective strategies for reducing its incidence is an important public health priority, especially in low-income countries, where resources for treating depression are scarce. We describe in this report an intervention development project, funded by the US National Institute of Mental Health, to address “indicated” prevention of depression in older adults attending rural and urban primary care clinics in Goa, India. Specifically, participants in the “DIL” (“Depression in Later Life”) trial were older adults living with mild, subsyndromal symptoms of depression and anxiety and thus at substantial risk for transitioning to fully syndromal major depression and anxiety disorders. Building upon the MANAS treatment trial (“Promoting Mental Health”) led by Patel et al. in the same locale, we present here lessons learned in the development and implementation of a protocol utilizing lay health counsellors (LHCs) who deliver a multi-component depression prevention intervention organized conceptually around Problem Solving Therapy for Primary Care (PST), with additional components addressing brief behavioural treatment of sleep disturbances such as insomnia, meeting basic social casework needs, and education in self-management of prevalent comorbid chronic diseases, such as diabetes mellitus. To our knowledge, DIL is the first randomized clinical trial addressing the prevention of depressive disorders ever conducted in a low- or middle-income country.

Objective To examine whether lifestyle factors, including sedentary time and physical activity, could independently contribute to risk of end-stage renal disease (ESRD).Study design Case-cohort study.Setting South-eastern USA.Participants The Southern Community Cohort Study recruited ~86 000 black and white participants from 2002 to 2009. We assembled a case cohort of 692 incident ESRD cases and a probability sample of 4113 participants.Predictors Sedentary time was calculated as hours/day from daily sitting activities. Physical activity was calculated as metabolic equivalent (MET)-hours/day from engagement in light, moderate and vigorous activities.Outcomes Incident ESRD.Results At baseline, among the subcohort, mean (SD) age was 52 (8.6) years, and median (25th, 75th centile) estimated glomerular filtration rate (eGFR) was 102.8 (85.9–117.9) mL/min/1.73 m2. Medians (25th–75th centile) for sedentary time and physical activity were 8.0 (5.5–12.0) hours/day and 17.2 (8.7–31.9) MET-hours/day, respectively. Median follow-up was 9.4 years. We observed significant interactions between eGFR and both physical activity and sedentary behaviour (p27 MET-hours/day. High levels of sitting time were associated with increased ESRD risk only among those with reduced kidney function (eGFR ≤30 mL/min/1.73 m2); this association was attenuated after excluding the first 2 years of follow-up.Conclusions In a population with a high prevalence of chronic kidney disease risk factors such as hypertension and diabetes, physical activity appears to be associated with reduced risk of ESRD among those with preserved kidney function. A positive association between sitting time and ESRD observed among those with advanced kidney disease is likely due to reverse causation.

Intralesional (IL) injection of Rose Bengal (PV-10) induces regression of injected and uninjected lesions in several murine tumor models. In this study, we investigated the anti-tumor response of combining IL PV-10 with blockade of the PD-1 / PD-L1 pathway and the role of immune cell populations in eliciting this response. To investigate the role of T cell subsets in mediating an immune response, B16 or M05 melanoma-bearing mice received combination therapy as well as CD8+, CD4+, or CD25+ depleting antibodies. Tumor growth was measured. T cells were collected from spleens or tumors, and phenotype, activation markers, and reactivity were measured. Splenocytes from mice treated with combination therapy had increased OVA antigen-specific CD8+ T cells in M05-tumor-bearing mice. Depletion of CD4+ T cells or regulatory T cells (Tregs) in combination with IL PV-10 and anti-PD-1 antibody treatment resulted in an enhanced anti-tumor effect. Treatment with CD8+ depleting antibody abrogated anti-tumor immunity. These results support a clinical study for the safety and anti-tumor immune responses with combination therapy of IL PV-10 and PD-1/PD-L1 blockade.

OBJECTIVES/SPECIFIC AIMS: The Life’s Simple 7 (LS7) metric was created by the American Heart Association with the goal of educating the public on seven modifiable factors that contribute to heart health. While it is well documented that these ideal health behaviors lower risk of cardiovascular disease (CVD) in the general population, the association between the LS7 ideal health metrics and end stage renal disease (ESRD) risk has not been examined in a lower socioeconomic population at high risk for both ESRD and CVD. Our objective is to examine the association between the LS7 score and incident ESRD in a cohort of white and black men and women in the southeastern US, where rates of CVD and ESRD are high. METHODS/STUDY POPULATION: The Southern Community Cohort Study recruited ~86,000 low-income blacks and whites in the southeastern US (2002-2009). Utilizing a nested case-control design, our analysis included 1628 incident cases of ESRD identified via linkage of the cohort with the United States Renal Data System (USRDS) from January 1, 2002 to March 31, 2015. Controls (n = 4884) were individually matched 3:1 with ESRD cases based on age, sex, and race. Demographic, medical, and lifestyle information were obtained via baseline questionnaire. The AHA definitions for ideal health were used for non-smoking (never or quit >12 months), body mass index (BMI75 min/week of vigorous physical activity or >150min/week of moderate/vigorous activity). Modified definitions were used for consuming a healthy diet [Healthy Eating Index (HEI10) score>70] and for blood pressure, fasting plasma glucose, and total cholesterol, based on self-reported no history of diagnosis of hypertension, diabetes, and hypercholesterolemia, respectively. The number of ideal health parameters were summed to generate the LS7 score, which ranged from 0-7 with higher scores indicating more ideal health. Adjusted odds ratios (95% confidence intervals) for incident ESRD associated with LS7 score were calculated using conditional logistic regression models, adjusting for income and education. The SCCS ESRD case-cohort dataset will be available by TS 2019 and analyses will be completed to adjust for baseline estimated glomerular filtration rate (eGFR) as a marker of kidney function and to examine whether eGFR modifies the relationship between LS7 and incident ESRD. RESULTS/ANTICIPATED RESULTS: At baseline, mean age was 54 years, 55% (3600) of participants were women, and 87% (5656) were black. A total of 58% (943) of ESRD cases were non-smokers compared to 54% (2633) of controls. ESRD cases had higher prevalence of BMI>25 kg/m2 (81% vs. 74%), hypertension (84% vs. 59%), hypercholesterolemia (48% vs. 34%), and diabetes (66% vs. 22%) compared to controls. A total of 18% (839) of controls and 12% (194) of ESRD cases met ideal exercise recommendations, and 20% of either cases (302) or controls (916) had a HEI10 score above 70. The median LS7 score for controls and ESRD cases was 3 and 2, respectively, and 17% (983) of participants had a low score (0-1) while 2% (105) met 6 or 7 ideal health metrics. Higher LS7 score was associated with lower odds of ESRD (P-trend3 (above median) had 75% reduced odds of ESRD (OR 0.25; 95% CI 0.22, 0.29) compared to those with a score of 2 or less. DISCUSSION/SIGNIFICANCE OF IMPACT: In the SCCS population, the presence of any 3 or more ideal health behaviors is associated with reduced odds of developing ESRD. The components of the LS7 represent important modifiable risk factors that may be targets for future interventions driven by the patient. The attributable risk due to each factor is needed to dissect which ideal behaviors are the most beneficial.

We provide a new description of the Pieri rule of the homology of the affine Grassmannian and an affineanalogue of the charge statistics in terms of bounded partitions. This makes it possible to extend the formulation ofthe Kostka–Foulkes polynomials in terms of solvable lattice models by Nakayashiki and Yamada to the affine setting.

We apply ideas from crystal theory to affine Schubert calculus and flag Gromov-Witten invariants. By defining operators on certain decompositions of elements in the type-$A$ affine Weyl group, we produce a crystal reflecting the internal structure of Specht modules associated to permutation diagrams. We show how this crystal framework can be applied to study the product of a Schur function with a $k$-Schur function. Consequently, we prove that a subclass of 3-point Gromov-Witten invariants of complete flag varieties for $\mathbb{C}^n$ enumerate the highest weight elements under these operators.

We introduce two families of symmetric functions with an extra parameter $t$ that specialize to Schubert representatives for cohomology and homology of the affine Grassmannian when $t=1$. The families are defined by a statistic on combinatorial objects associated to the type-$A$ affine Weyl group and their transition matrix with Hall-Littlewood polynomials is $t$-positive. We conjecture that one family is the set of $k$-atoms.

Using the expansion of the inverse of the Kostka matrix in terms of tabloids as presented by Eğecioğlu and Remmel, we show that the fusion coefficients can be expressed as an alternating sum over cylindric tableaux. Cylindric tableaux are skew tableaux with a certain cyclic symmetry. When the skew shape of the tableau has a cutting point, meaning that the cylindric skew shape is not connected, or if its weight has at most two parts, we give a positive combinatorial formula for the fusion coefficients. The proof uses a slight modification of a sign-reversing involution introduced by Remmel and Shimozono. We discuss how this approach may work in general.

We give a new description of the Pieri rule for $k$-Schur functions using the Bruhat order on the affine type-$A$ Weyl group. In doing so, we prove a new combinatorial formula for representatives of the Schubert classes for the cohomology of affine Grassmannians. We show how new combinatorics involved in our formulas gives the Kostka-Foulkes polynomials and discuss how this can be applied to study the transition matrices between Hall-Littlewood and $k$-Schur functions.