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Fabrics—materials consisting of layers of woven fibres—are some of the most important materials in everyday life1. Previous nanoscale weaves2–16 include isotropic crystalline covalent organic frameworks12–14 that feature rigid helical strands interlaced in all three dimensions, rather than the two-dimensional17,18 layers of flexible woven strands that give conventional textiles their characteristic flexibility, thinness, anisotropic strength and porosity. A supramolecular two-dimensional kagome weave15 and a single-layer, surface-supported, interwoven two-dimensional polymer16 have also been reported. The direct, bottom-up assembly of molecular building blocks into linear organic polymer chains woven in two dimensions has been proposed on a number of occasions19–23, but has not previously been achieved. Here we demonstrate that by using an anion and metal ion template, woven molecular ‘tiles’ can be tessellated into a material consisting of alternating aliphatic and aromatic segmented polymer strands, interwoven within discrete layers. Connections between slowly precipitating pre-woven grids, followed by the removal of the ion template, result in a wholly organic molecular material that forms as stacks and clusters of thin sheets—each sheet up to hundreds of micrometres long and wide but only about four nanometres thick—in which warp and weft single-chain polymer strands remain associated through periodic mechanical entanglements within each sheet. Atomic force microscopy and scanning electron microscopy show clusters and, occasionally, isolated individual sheets that, following demetallation, have slid apart from others with which they were stacked during the tessellation and polymerization process. The layered two-dimensional molecularly woven material has long-range order, is birefringent, is twice as stiff as the constituent linear polymer, and delaminates and tears along well-defined lines in the manner of a macroscopic textile. When incorporated into a polymer-supported membrane, it acts as a net, slowing the passage of large ions while letting smaller ions through. An anion and metal ion template is used to form woven polymer patches that are joined together by polymerization into a fully woven, two-dimensional, molecular patchwork.

The properties of knots are exploited in a range of applications, from shoelaces to the knots used for climbing, fishing and sailing1. Although knots are found in DNA and proteins2, and form randomly in other long polymer chains3,4, methods for tying5 different sorts of knots in a synthetic nanoscale strand are lacking. Molecular knots of high symmetry have previously been synthesized by using non-covalent interactions to assemble and entangle molecular chains6-15, but in such instances the template and/or strand structure intrinsically determines topology, which means that only one type of knot is usually possible. Here we show that interspersing coordination sites for different metal ions within an artificial molecular strand enables it to be tied into multiple knots. Three topoisomers-an unknot (01) macrocycle, a trefoil (31) knot6-15, and a three-twist (52) knot-were each selectively prepared from the same molecular strand by using transition-metal and lanthanide ions to guide chain folding in a manner reminiscent of the action of protein chaperones16. We find that the metal-ion-induced folding can proceed with stereoinduction: in the case of one knot, a lanthanide(III)-coordinated crossing pattern formed only with a copper(I)-coordinated crossing of particular handedness. In an unanticipated finding, metal-ion coordination was also found to translocate an entanglement from one region of a knotted molecular structure to another, resulting in an increase in writhe (topological strain) in the new knotted conformation. The knot topology affects the chemical properties of the strand: whereas the tighter 52 knot can bind two different metal ions simultaneously, the looser 31 isomer can bind only either one copper(I) ion or one lutetium(III) ion. The ability to tie nanoscale chains into different knots offers opportunities to explore the modification of the structure and properties of synthetic oligomers, polymers and supramolecules.

The large instruction working sets of private and public cloud workloads lead to frequent instruction cache misses and costs in the millions of dollars. While prior work has identified the growing importance of this problem, to date, there has been little analysis of where the misses come from, and what the opportunities are to improve them. To address this challenge, this paper makes three contributions. First, we present the design and deployment of a new, always-on, fleet-wide monitoring system, AsmDB, that tracks front-end bottlenecks. AsmDB uses hardware support to collect bursty execution traces, fleet-wide temporal and spatial sampling, and sophisticated offline post-processing to construct full-program dynamic control-flow graphs. Second, based on a longitudinal analysis of AsmDB data from real-world online services, we present two detailed insights on the sources of front-end stalls: (1) cold code that is brought in along with hot code leads to significant cache fragmentation and a corresponding large number of instruction cache misses; (2) distant branches and calls that are not amenable to traditional cache locality or next-line prefetching strategies account for a large fraction of cache misses. Third, we prototype two optimizations that target these insights. For misses caused by fragmentation, we focus on memcmp, one of the hottest functions contributing to cache misses, and show how fine-grained layout optimizations lead to significant benefits. For misses at the targets of distant jumps, we propose new hardware support for software code prefetching and prototype a new feedback-directed compiler optimization that combines static program flow analysis with dynamic miss profiles to demonstrate significant benefits for several large warehouse-scale workloads. Improving upon prior work, our proposal avoids invasive hardware modifications by prefetching via software in an efficient and scalable way. Simulation results show that such an approach can eliminate up to 96% of instruction cache misses with negligible overheads.

Patients with metabolic syndrome (MS) may have increased perioperative morbidity and mortality. The aim of this analysis was to investigate the association of MS with mortality, serious morbidity, and pancreatectomy-specific outcomes in patients undergoing pancreatoduodenectomy (PD).Patients with MS who underwent PD were selected from the 2014-2018 ACS-NSQIP pancreatectomy-specific database. MS was defined as obesity (BMI ≥ 30 kg/mOf 19,054 patients who underwent PD, 7.3% (n = 1388) had MS. On univariable analysis, patients with MS had significantly worse outcomes (p 0.05): 30-day mortality (3% vs 1.8%), serious morbidity (26% vs 23%), re-intubation (4.9% vs 3.5%), pulmonary embolism (2.0% vs 1.1%), acute renal failure (1.5% vs 0.9%), cardiac arrest (1.9% vs 1.0%), and delayed gastric emptying (18% vs 16.5%). On multivariable analysis, 30-day mortality was significantly increased in patients with MS (aOR: 1.53, p 0.01).Metabolic syndrome is associated with increased morbidity and mortality in patients undergoing pancreatoduodenectomy. The association with mortality is a novel observation. Perioperative strategies aimed at reduction and/or mitigation of cardiac, pulmonary, thrombotic, and renal complications should be employed in this population given their increased risk.

The introduction of more effective chemotherapy a decade ago has led to increased use of neoadjuvant therapy (NAT) in patients with pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to assess the evolving use of NAT in individuals with PDAC undergoing pancreatoduodenectomy (PD) and to compare their outcomes with patients undergoing upfront operation.The American College of Surgeons NSQIP Procedure Targeted Pancreatectomy database was queried from 2014 to 2019. Patients undergoing pancreatoduodenectomy were evaluated based on the use of NAT versus upfront operation. Multivariable analysis was performed to determine the effect of NAT on postoperative outcomes, including the composite measure optimal pancreatic surgery (OPS). Mann-Kendall trend tests were performed to assess the use of NAT and associated outcomes over time.A total of 13,257 patients were identified who underwent PD for PDAC between 2014 and 2019. Overall, 33.6% of patients received NAT. The use of NAT increased steadily from 24.2% in 2014 to 42.7% in 2019 (p0.0001). On multivariable analysis, NAT was associated with reduced serious morbidity (odds ratio [OR] 0.83, p0.001), clinically relevant pancreatic fistulas (OR 0.52, p0.001), organ space infections (OR 0.74, p0.001), percutaneous drainage (OR 0.73, p0.001), reoperation (OR 0.76, p = 0.005), and prolonged length of stay (OR 0.63, p0.001). OPS was achieved more frequently in patients undergoing NAT (OR 1.433, p0.001) and improved over time in patients receiving NAT (50.7% to 56.6%, p0.001).NAT before pancreatoduodenectomy increased more than 3-fold over the past decade and was associated with improved optimal operative outcomes.

More complex cases are being performed robotically. This study aims to characterize trends in robotic pancreatoduodenectomy (RPD) over time and assess opportunities for advanced trainees.Using the ACS-NSQIP database from 2014 to 2019, PD cases were characterized by operative approach (open-OPN, laparoscopic-LAP, robotic-ROB). Proficiency and postoperative outcomes were described by approach over time.24,268 PDs were identified, with the ROB approach increasing from 2.8% to 7.5%. Unplanned conversion increased over time for LAP (27.7-39.0%, p = 0.003) but was unchanged for ROB cases (14.8-14.7%, p = 0.257). Morbidity increased for OPN PD (35.5-36.8%, p = 0.041) and decreased for ROB PD (38.7-30.3%, p = 0.010). Mean LOS was lower in ROB than LAP/OPN (9.5 vs. 10.9 vs. 10.9 days, p 0.00001). Approximately, 100 AHPBA, SSO, and ASTS fellows are being trained each year in North America; however, only about 5 RPDs are available per trainee per year which is far below that recommended to achieve proficiency.Over a 6-year period, a significant increase was observed in the use of RPD without a concomitant increase in conversion rates. RPD was associated with decreased morbidity and length of stay. Despite this shift, the number of cases being performed is not adequate for all fellows to achieve proficiency before graduation.

The use of propensity score methods in the surgical literature is increasing. Randomized, controlled clinical trials are the gold standard of medical research, allowing for accurate measurement and analysis of treatment effects. Use of propensity score methods allows researchers to mimic randomization when true randomization may not be possible. When used properly, these methods are a powerful tool for the medical researcher, allowing more rigorous conclusions to be drawn from retrospective data. With the increasing prevalence of propensity methods, it is important that these methods are used correctly, lest researchers be led to misleading conclusions based on poor statistical study design and analysis. The objective of this review is to analyze and evaluate the use of propensity score methods in the surgical oncology literature. We critique the current state of the use of propensity scores in the surgical oncology literature and offer recommendations to assure appropriate usage of propensity score methods.

We report on the stereoselective synthesis of trefoil knots of single topological handedness in up to 90% yield (over two steps) through the formation of trimeric circular helicates from ligand strands containing either imine or, unexpectedly, amide chelating units and metal ion templates of the appropriate coordination character (zinc(II) for imines; cobalt(III) for amides). The coordination stereochemistry of the octahedral metal complexes is determined by asymmetric carbon centers in the strands, ultimately translating into trefoil knots that are a single enantiomer, both physically and in terms of their fundamental topology. Both the imine-zinc and amide-cobalt systems display self-sorting behavior, with racemic ligands forming knots that individually contain only building blocks of the same chirality. The knots and the corresponding trimeric circular helicate intermediates (Zn(II)

Background: Hematologic toxicity (HT) commonly occurs during chemoradiation therapy (CRT) for esophageal cancer. We sought to determine radiation doses that correlate with declines in blood counts due to vertebral body (VB) irradiation during CRT. Methods: We analyzed 53 esophageal cancer patients who were treated with weekly neoadjuvant carboplatin, paclitaxel and RT with weekly complete blood counts (CBC) available during treatment. HTs were graded according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). Dose volume histogram (DVH) parameters of Vx, defined as percentage of entire bony vertebra (body, pedicles, laminae, processes) receiving at least x Gy of radiation, were collected for VB V 5 (VBV 5 ), VBV 10 –VBV 60 in increments of 10, and mean vertebral dose (MVD). Linear and logistic regressions were performed to identify associations between leukopenia nadirs and DVH parameters. Receiver operator curves identified thresholds to avoid grade ≥3 leukopenia. Results: A proportion of 32.1% of patients (n=17) developed grade 3 leukopenia and 5.7% (n=3) developed grade 4 leukopenia. VBV 5 , VBV 10 , VBV 20 , VBV 30 , and MVD were significantly associated with worsening leukopenia on univariate and multivariate analysis. Associations with leukopenia were not seen with VBV 40 and VBV 50 DVH values. Thresholds to avoid grade ≥3 leukopenia were VBV 10

Background Post-operative pulmonary complications (POPC) are common in patients undergoing esophagectomy and neoadjuvant radiotherapy may exacerbate POPC. This study assessed whether neoadjuvant radiation increases the incidence of POPC in patients undergoing esophagectomy for malignancy. Methods The American College of Surgeons-National Surgical Quality Improvement Program database files from 2016 to 2018 were queried for patients undergoing esophagectomy for malignancy. Inverse probability treatment weighting (IPTW) was used to create balanced cohorts in which the control group received neoadjuvant chemotherapy (nCT) and the treatment cohort received neoadjuvant chemoradiotherapy (nCRT). A subset analysis was performed on patients with pre-existing pulmonary disease (PEPD). Primary outcomes were POPC and 30-day mortality. Results The all-patient analysis did not demonstrate a consistent association between neoadjuvant radiation and POPC. However, in patients with PEPD, POPC occurred more often in the nCRT cohort. Comparing nCRT to nCT and after IPTW adjustment for confounders, there was higher odds of pneumonia (aOR = 3.0, P = .002), unplanned intubation (aOR = 2.0, P = .03), and extended mechanical ventilation (aOR = 3.6, P = .002). Discussion In esophageal cancer patients with PEPD that undergo nCRT vs nCT prior to esophagectomy, the greater risk of POPCs must be weighed against the potential for improved oncologic outcomes.

Historically, the interlacing of strands at the molecular level has mainly been limited to coordination polymers and DNA. Despite being proposed on a number of occasions, the direct, bottom-up assembly of molecular building blocks into woven organic polymers remained an aspirational, but elusive, target for several decades. However, recent successes in two-dimensional and three-dimensional molecular-level weaving now offer new opportunities and research directions at the interface of polymer science and molecular nanotopology. This Perspective provides an overview of the features and potential of the periodic nanoscale weaving of polymer chains, distinguishing it from randomly entangled polymer networks and rigid crystalline frameworks. We review the background and experimental progress so far, and conclude by considering the potential of molecular weaving and outline some of the current and future challenges in this emerging field.

BACKGROUND Preoperative malnutrition adversely impacts perioperative outcomes among patients with gastrointestinal (GI) cancer. The attributable risk (AR) that nutrition status contributes towards negative outcomes is poorly understood. METHODS Adults undergoing GI cancer surgeries were identified within the American College of Surgeons National Surgical Quality Improvement Program database (2005-2017). Emergency surgeries, outpatients, and cases with an American Society of Anesthesiologists status above III were excluded. Adjusted multivariable models were constructed to determine the associations between markers of nutrition status (body mass index, >10% weight loss in last 6 months, functional status, and serum albumin level) and adverse perioperative outcomes (presence and number of complications, death, 30-day readmission, and length of stay). Predictive accuracy statistics and population AR (PAR) were determined. RESULTS The final sample included 78,662 cases. Patients with >10% weight loss 6 months preceding surgery (compared with those who did not), had a significantly increased risk of complications (Relative Risk = 1.28; 95% CI, 1.20-1.37) and odds of death (odds ratio [OR] = 1.37; 95% CI, 1.18-1.59). A totally dependent functional status (compared with independent status) was associated with a 3.3-times higher odds of death (OR = 3.30; 95% CI, 1.53-7.15). Multivariable models were not predictive of adverse outcomes; PAR from the markers ranged 1%-2%. CONCLUSION Ten percent weight loss in preceding 6 months was associated with increased risk of adverse perioperative outcomes among adults undergoing GI cancer surgery. The contribution of nutrition status markers to surgical outcomes as assessed by PAR was small (1%-2%), a finding not previously reported. Future intervention studies should include validated nutrition risk markers, control for effects of perioperative variables, and evaluate PAR within the immediate/long-term postoperative periods.

Cannabinoids have been used medicinally for thousands of years. Clinical trials support their use for treatment of chemotherapy-induced nausea and vomiting and HIV- and AIDS-related anorexia. Cancer anorexia cachexia syndrome (CACS) is a common debilitating condition and is associated with poor prognosis. The 2016 European Society for Parenteral and Enteral Nutrition clinical guidelines on nutrition in cancer patients concluded that "there are insufficient consistent clinical data to recommend cannabinoids to improve taste disorders or anorexia in cancer patients." The increased attention that cannabinoids have received in recent years warrants an updated evaluation of the literature on this topic, as practitioners are likely to encounter cancer patients interested in cannabinoid use. A systematic literature search was performed to assess the current body of evidence concerning cannabinoid use for the stimulation of appetite and oral intake by cancer patients. Over the past 20 years, 6 randomized controlled trials have evaluated the impact of cannabinoids on appetite-related outcomes in oncology patients in comparison with a control group or placebo. Based on this literature, cannabinoids do not appear to improve appetite, oral intake, weight, chemosensory function, or appetite-related quality of life. Limitations of the literature include small sample sizes, lack of adjustment for confounding variables, and difficulties conducting true placebo-controlled trials with a drug that may result in psychoactive side effects. Further exploration of the impact of cannabinoid use on CACS by using large, well-designed clinical trials is needed.

PURPOSE/OBJECTIVE(S) Neoadjuvant chemoradiotherapy (CRT) serves to downstage and increase the rate of surgical resection for borderline resectable and resectable pancreatic adenocarcinoma ((B)RPC). Although conventional staging provides prognostic information, it remains a challenge to predict which patients will proceed with resection. We hypothesize that the severity of vessel involvement and the trajectory of CA19-9 levels after neoadjuvant treatment would associate with proceeding to resection. MATERIALS/METHODS Medical records were retrospectively reviewed at a single center for patients diagnosed with (B)RPC and treated with neoadjuvant CRT between 1/2005 and 12/2020. Progress notes were evaluated to determine if a patient proceeded to surgery and the trajectory of CA 19-9 levels in response to treatment. Radiologist notes were evaluated to determine the extent of mesenteric vessel (superior mesenteric artery, celiac axis, portal vein, hepatic artery, and superior mesenteric vein) involvement. A vessel involvement score was calculated as the sum of all vessels in contact with tumor: 1 point for each vessel, with partial (< 180 degrees) encasement of artery counting as 2 points. Odds ratios (OR) of proceeding to resection were computed with 95% confidence intervals (CI) for CA19-9 response to treatment. Ordinal logistic regression models were fit to estimate the impact of greater vessel involvement on the odds of NOT proceeding with surgery. RESULTS Forty-two (n = 42) patients were included in the analysis. The median age was 65 years (IQR: 61 to 71). 73% of patients were treated with 3600 cGy in 15 fractions (fx), 24% of patients were treated with 4500-5040 cGy in 25-28 fx, and 3% of patients were treated with 3300 cGy in 5 fx. 55% of patients were treated with neoadjuvant FOLFIRINOX and 45% of patients were treated with other regimens. 88% of patients were considered borderline resectable and 12% were resectable at the time of diagnosis. Patients with any decrease in CA19-9 levels after CRT had higher odds of proceeding with resection (OR = 21.0, 95% CI: 3.2 to 139.2). However, decrease in CA19-9 levels after upfront chemotherapy was not significantly associated with proceeding with resection (P = 0.91). The odds of NOT proceeding with resection after neoadjuvant CRT were 1.81 times higher (95% CI: 0.97 to 3.39) for each increase in vessel involvement score, however these findings were not statistically significant (P = 0.062). CONCLUSION Patients diagnosed with (B)RPC proceeding with CRT have different odds of proceeding to surgery based on their response to CRT and extent of vessel involvement. Post-CRT CA19-9 can help predict which patients may proceed to resection. Future investigations will develop nomograms for estimating odds of proceeding to surgery in larger datasets to help aid in patient counseling and multidisciplinary discussion.

Purpose/Objective(s) Radiation therapy (RT) is a critical modality for the treatment of unresectable hepatocellular carcinoma (HCC). Little is known about how the etiology of HCC impacts overall and progression free survival (OS and PFS) in patients treated with definitive RT. We hypothesize that patients treated with definitive RT for HCC secondary to hepatitis B and hepatitis C viruses (viral group) would have favorable OS and PFS when compared to patients with HCC secondary to other etiologies (non-viral group). Materials/Methods Medical records were retrospectively reviewed at a single institution for patients diagnosed with unresectable HCC and treated with definitive RT between 1/2011 and 12/2020. Patients treated with prior surgery or radiofrequency ablation were excluded. Progress notes were reviewed to determine date of last follow-up, progression, and death. Notes were also assessed to determine the etiology of HCC, age at diagnosis, Child-Pugh classification (CPC), AJCC 8th edition T stage, RT strategy, and planning target volume (PTV). Descriptive statistics were quantified for baseline characteristics. Survival curves were estimated via Kaplan-Meier method; statistical difference was determined using the log-rank test. Multivariate (MVA) Cox proportional hazards analysis was conducted to estimate hazard ratios (HR) when controlling for confounding factors. Results Forty-six patients were included in the analysis. 30 (65%) patients were in the viral group, while 16 (35%) patients were in the non-viral group. Median ages at diagnosis for the viral and non-viral groups were 64 (interquartile range (IQR): 60 to 69) and 71 years (IQR: 66.5 to 76.5), respectively (P = 0.014). Treatment with hypofractionated RT (P = 0.559), proton therapy (P = 0.686), performance status (P = 0.222), CPC (P = 0.270), T stage (P = 0.639), and PTV (P = 0.472) were not different between groups. There was a trend toward improved Median OS for the viral group compared to the non-viral group: 17.9 months (95% confidence interval (CI): 9.7 to not-reached (NR)) vs. 8.8 months (95% CI: 6.1 to NR) (P = 0.072). Similarly, PFS was not different between viral and non-viral groups: 9.3 (95% CI: 7.4 to 19.0) vs. 8.0 (95% CI: 4.0 to 10.3), P = 0.314. However, after controlling for confounding factors with MVA Cox proportional hazards models, the viral group had superior OS (HR = 4.20, 95% CI: 1.47 to 12.02, P = 0.008); the viral group also had superior PFS (HR = 2.48, 95% CI: 1.06 to 5.81, P = 0.037). Conclusion Our retrospective review of patients with unresectable HCC treated with definitive RT provides evidence that viral etiologies of HCC may fare better in OS and PFS when compared to non-viral etiologies. The etiology of HCC development for virally vs non-virally mediated tumors may have implications for treatment and response in the setting of radiation therapy.

Although circular helicates can be assembled with a range of labile transition-metal centers, solely "chiral-at-metal" examples (i.e., systems without chiral ligands) and heterometallic (i.e., mixed metal systems, racemic or chiral) circular helicates both remain unexplored. Here, we report on the enantioselective synthesis of a heterometallic (Ir2Zn4) hexameric circular helicate and its elaboration into the corresponding triply interlocked Star of David [2]catenane. The relative inertness of Ir(III) enables enantiospecific synthesis of the hexameric circular helicate using chiral-at-metal building blocks. The resulting Star of David [2]catenane, which is a chiral 6-2-1 link, is formed as a single topological enantiomer. The X-ray crystal structure of the (Ir2Zn4)-catenane shows each of the two 95-atom-long macrocycles entwined around the six metal octahedral metal ions and each other, forming a triply interlocked circular double helix. Two PF6- anions reside above and below the central cavity. The Star of David [2]catenane, both with and without coordinated Zn(II) ions, retains the photophysical properties characteristic of cyclometalated Ir(III) complexes. The synthetic strategy opens up new research directions and opportunities for the assembly of other chiral knots, links, and heterometallic circular helicates.

A (FeII)6-coordinated triply interlocked (“Star of David”) [2]catenane (612 link) and a (FeII)5-coordinated pentafoil (51) knot are found to selectively transport anions across phospholipid bilayers. Allostery, topology, and building block stoichiometry all play important roles in the efficacy of the ionophoric activity. Multiple FeII cation coordination by the interlocked molecules is crucial: the demetalated catenane exhibits no anion binding in solution nor any transmembrane ion transport properties. However, the topologically trivial, Lehn-type cyclic hexameric FeII helicates—which have similar anion binding affinities to the metalated Star of David catenane in solution—also display no ion transport properties. The unanticipated difference in behavior between the open- and closed-loop structures may arise from conformational restrictions in the linking groups that likely enhances the rigidity of the channel-forming topologically complex molecules. The (FeII)6-coordinated Star of David catenane, derived from a hexameric cyclic helicate, is 2 orders of magnitude more potent in terms of ion transport than the (FeII)5-coordinated pentafoil knot, derived from a cyclic pentamer of the same building block. The reduced efficacy is reminiscent of multisubunit protein ion channels assembled with incorrect monomer stoichiometries.

Background Malnutrition is common among patients with gastrointestinal (GI) cancer and contributes to their morbidity and mortality. Nutrition interventions provided by a registered dietitian (RD) or dietitian may improve nutrition status and patient outcomes; however, there are few studies that attempt to define the contribution of the dietitian to these outcomes. Objective Our objective was to identify the value added by the dietitian to the care of patients with GI malignancies. Methods A structured review was conducted using PubMed, CINAHL, Scopus, Medline, and ClinicalKey (all dates up to December 2019). Patients included those with GI malignancies undergoing cancer treatment and receiving intervention provided by an dietitian. Intervention included provision of medical nutrition therapy by an dietitian in the form of counseling, diet advice, oral nutritional supplementation, and enteral and/or parenteral nutrition-directed recommendations. Results Ten relevant studies were identified and included for analysis. Studies suggest that nutrition counseling by a dietitian during cancer treatment results in improved weight maintenance and energy intake. Preoperative nutrition counseling and inpatient dietitian intervention seem to decrease length of stay after major surgery. Conclusions We conclude that the dietitian, especially when providing nutrition counseling, improves the nutrition-related outcomes of patients with GI malignancies. The small number of existent studies highlights the need for further research to define the impact of dietitian interventions and to determine which particular interventions best improve patient outcomes.

Study objective Whether having an emergency manual (EM) available for use during perioperative crises enhances or detracts from team performance, especially for multi-factorial diagnostic situations that do not explicitly match a chapter of the EM. Design A simulation-based, prospective randomized trial based upon two perioperative crises, one involving a patient with a transfusion reaction for which the EM contains a specific chapter, and the other involving a patient with refractory hypotension progressing into septic shock for which the EM does not have a specific chapter. Setting 52 regularly scheduled 6-h courses at the Center for Medical Simulation in Boston, Massachusetts, USA. Study group 304 US-trained practicing anesthesiologists. Interventions The absence or presence of the EM during the simulation case. Measurements Teams were rated in the following categories: primary underlying diagnosis, fluid resuscitation, treatment of primary diagnosis, cardiac arrest management, overall crisis management, and (if applicable) EM usage. Also, raters recorded free-text ‘field notes’ about the usage-patterns and perceived utility of the EM. Using these ‘field notes’ and a two-stage, inductively revised procedure, two independent reviewers examined a subset of case videos for action analysis. Main results Performance ratings for a total of 51 teams and 95 simulations were included in the final analysis. No effect on performance was demonstrated with providing the EM in either the refractory hypotension/septic shock case or the transfusion reaction case, with the exception of the PEA arrest category. In the subset of simulations in which resuscitation from PEA arrest performance could be evaluated, EM availability was associated with an adjusted mean 1.3 point (99% confidence interval [CI]: 0.2, 2.4) improvement in performance in the transfusion reaction case (p = 0.004), but only an adjusted mean 0.2 point (99% CI, −0.7, 1.1) improvement in the refractory hypotension/septic shock case (p = 0.530) (p for interaction = 0.069). Analysis of actions found that when available, the EM was usually used, but often not until after cardiac arrest had occurred. In some cases, teams persisted with incorrect diagnoses and treatments irrespective of the presence or absence of an EM. Conclusions Providing an EM did not affect team performance in areas like diagnosis, treatment, fluid resuscitation, communication, and teamwork in management of perioperative crises such as transfusion reaction where an explicit chapter in the EM exists and refractory hypotension / septic shock where an explicit chapter does not exist. A suggestion of improved cardiac arrest resuscitation with the availability of an EM was found, but should be interpreted with caution given a limited sample size. Observed actions using the EM demonstrated that only about half of the teams used the EM to any substantive degree and most used it relatively late in the crisis. By observation, the EM appeared to be helpful in about half of the cases and did not, by itself, deter from appropriate management.

Purpose: According to the American Joint Committee on Cancer (AJCC) 7th edition, T1 staging of pancreatic adenocarcinoma (PC) is defined as tumor limited to the pancreas, ≤2 cm. The AJCC 8th edition subcategorizes T1 staging into T1a (≤5 mm), T1b (≤1 cm), and T1c (≤2 cm) for PC despite the absence of supporting evidence. We sought to determine whether this new subcategorization has prognostic significance. Methods: A retrospective review of patients undergoing definitive surgery for PC was performed by using the National Cancer Database (NCDB) from 2004 to 2014. Kaplan–Meier survival was computed for the subcategories. Multivariable analysis (MVA) was performed by using stepwise regression. Results: The NCDB captured 41,552 stages I and II patients who underwent definitive surgery for PC in this 10-year period. A total of 2090 of these patients were pathological T1N0. The 5-year overall survival (OS) for patients with T1a (n = 319), T1b (n = 296), and T1c (n = 1309) PC was 68.8%, 57%, and 46.6%, respectively. This subcategorization lost significance on MVA and when focused on T1N1-2 patients. Recategorizing T stage into T1a (≤1 cm) and T1b (≤2 cm) resulted in statistical significance on MVA. Conclusion: Subcategorization of the T1 stage into T1a, T1b, and T1c in resected PC does differentiate OS in patients with node-negative disease. We support the AJCC 8th edition T1 stage subcategorization, while understanding that it does not differentiate OS on MVA. When this is further subcategorized into T1a (≤1 cm) and T1b (≤2 cm), it predicts OS in resected, node-negative patients on MVA.

Speculation with transactional memory systems helps pro- grammers and compilers produce profitable thread-level parallel programs. Prior work shows that supporting transactions that can span multiple threads, rather than requiring transactions be contained within a single thread, enables new types of speculative parallelization techniques for both programmers and parallelizing compilers. Unfortunately, software support for multi-threaded transactions (MTXs) comes with significant additional inter-thread communication overhead for speculation validation. This overhead can make otherwise good parallelization unprofitable for programs with sizeable read and write sets. Some programs using these prior software MTXs overcame this problem through significant efforts by expert programmers to minimize these sets and optimize communication, capabilities which compiler technology has been unable to equivalently achieve. Instead, this paper makes speculative parallelization less laborious and more feasible through low-overhead speculation validation, presenting the first complete design, implementation, and evaluation of hardware MTXs. Even with maximal speculation validation of every load and store inside transactions of tens to hundreds of millions of instructions, profitable parallelization of complex programs can be achieved. Across 8 benchmarks, this system achieves a geomean speedup of 99% over sequential execution on a multicore machine with 4 cores.

PURPOSE/OBJECTIVE(S) Neoadjuvant chemoradiotherapy is a critical treatment for borderline resectable and resectable pancreatic adenocarcinoma ((B)RPC). The PREOPANC trials employ a short course chemoradiation (SCCRT) regimen of 3600 cGy in 15 fractions with concurrent gemcitabine (GEM)-based chemotherapy, but little is known about the relative efficacy of capecitabine (CAPE)-based concurrent chemotherapy in this population. We hypothesize that patients treated with SCCRT with CAPE-based concurrent chemotherapy will have superior overall survival (OS) compared to GEM-based strategies. MATERIALS/METHODS Medical records were retrospectively reviewed at a single center for patients diagnosed with (B)RPC between 1/2005 and 12/2020. Patients treated with neoadjuvant SCCRT were included in the analysis. Descriptive statistics were quantified for baseline characteristics. OS was estimated using Kaplan-Meier estimates, statistical difference was determined using the log-rank test. Multivariate Cox proportional hazards analysis was conducted to estimate hazard ratios (HR) when controlling for confounding factors. RESULTS Thirty-one (n = 31) patients were included in the analysis. 71% of patients (n = 22) were treated with CAPE-based concurrent chemotherapy, while 29% of patients (n = 9) were treated with GEM-based concurrent chemotherapy. Median age at diagnosis was 65 (interquartile range (IQR): 60 to 71) for the CAPE group, compared to 66 (IQR: 63 to 71) for the GEM group, P = 0.414. 100% of patients in the CAPE group were borderline resectable, compared to 82% of patients in the GEM group, P = 0.171. 44% of patients in the CAPE group were treated with neoadjuvant FOLFIRINOX, compared to 14% in the GEM group, P = 0.016. Patients treated with concurrent 5-CAPE-based chemotherapy had a longer median OS than other concurrent chemotherapy approaches: Not reached (95% confidence interval (CI): 24 to not reached) vs. 17 months (95% CI: 6 to 22 months), P < 0.0001. Multivariate Cox proportional hazards models, controlling for borderline vs. resectable status, age at diagnosis, and use of neoadjuvant FOLFIRINOX, demonstrated that CAPE-based concurrent chemotherapy had a HR of death of 0.081 (95% CI: 0.018 to 0.369, P = 0.0012) compared to GEM-based concurrent chemotherapy. CONCLUSION Patients diagnosed with (B)RPC have many therapeutic options; this study suggests a benefit to CAPE-based concurrent chemotherapy when treating patients with SCCRT, even after controlling for significant confounding by greater use of neoadjuvant FOLFIRINOX with CAPE-based concurrent chemotherapy. SCCRT may be more effective with concurrent capecitabine instead of concurrent gemcitabine for (B)RPC.