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Acute colonic pseudo-obstruction (ACPO) is a condition characterized by acute dilation of the large bowel without evidence of mechanical obstruction that occurs in a variety of hospitalized patients with many predisposing factors. Management includes supportive care and limitation of offending medications with mainstays of treatment of neostigmine administration and colonic decompression. We report the case of a critically ill patient with ACPO who experienced bradycardia and a brief episode of asystole when receiving concomitant dexmedetomidine and neostigmine infusions but who later remained hemodynamically stable when receiving propofol and neostigmine infusions. The bradycardia and associated hemodynamic instability experienced while on dexmedetomidine and neostigmine infusions were rapidly corrected with atropine and cessation of offending agents. Because ACPO is encountered frequently and the use of dexmedetomidine as a sedative agent in the ICU is increasing, practitioners should be aware of the additive risk of bradycardia and potential for asystole with the combination of neostigmine and dexmedetomidine. Electronic drug interaction databases should be updated and drug information sources should include a drug-drug interaction between dexmedetomidine and neostigmine to reduce the likelihood of concomitant administration.

Uncovering links between processing conditions, microstructure, and properties is a central tenet of materials analysis. It is well known that microstructure determines properties, but expressing these structural features in a universal quantitative fashion has proved to be extremely difficult. Recent efforts have focused on training supervised learning algorithms to place microstructure images into predefined classes, but this approach assumes a level of a priori knowledge that may not always be available. In this paper, we expand this idea to the semi-supervised context in which class labels are known with confidence for only a fraction of the microstructures that represent the material system. It is shown that classifiers which perform well on both the high-confidence labeled data and the unlabeled, ambiguous data can be constructed by relying on the labeling consensus of a collection of semi-supervised learning methods. We also demonstrate the use of novel error estimation approaches for unlabeled data to establish robust confidence bounds on the classification performance over the entire microstructure space.

Both plasmonic and photonic materials manipulate light by structurally-defined optical properties. While photonic architectures can promote the scattering and reflection of certain wavelengths of light, plasmonic materials have plasmon resonances that confine light at the nanoscale. Coupling photonic materials to plasmon resonances could enhance the plasmonic response via wavelength-dependent interference and confinement properties. Here we explore the use of wavelength-dependent, naturally-abundant photonic crystal structures found in butterfly wings as substrates for plasmonic nanoparticle deposition, and probe the plasmonic–photonic interactions using surface-enhanced Raman spectroscopy. To better understand the wavelength dependence of field enhancement and localization of these systems, we examined the SERS responses of plasmonic nanoparticles deposited on four different butterfly wing colors with three excitation wavelengths. We find that excitation at wavelengths most closely matching the butterfly wing color produces the most intense SERS signal, with signal magnitude increases up to an order of magnitude, beyond a mere additive effect. These naturally abundant photonic structures show potential to create cheaper, wavelength-selective SERS substrates, and they provide a quantitative insight on plasmon–photonic crystal coupling.

One of the key questions regarding COVID19 vaccines is whether they can reduce viral shedding. To date, Israel vaccinated substantial parts of the adult population, which enables extracting real world signals. The vaccination rollout started on Dec 20th 2020, utilized mainly the BNT162b2 vaccine, and focused on individuals who are 60 years or older. By now, more than 75% of the individuals of this age group have been at least 14 days after the first dose, compared to 25% of the individuals between ages 40-60 years old. Here, we traced the Ct value distribution of 16,297 positive qPCR tests in our lab between Dec 1st to Jan 31st that came from these two age groups. As we do not have access to the vaccine status of each test, our hypothesis was that if vaccines reduce viral load, we should see a difference in the Ct values between these two age groups in late January but not before. Consistent with this hypothesis, until Jan 15th, we did not find any statistically significant differences in the average Ct value between the groups. In stark contrast, our results in the last two weeks of January show a significant weakening in the average Ct value of 60+ individuals to the 40-60 group. To further corroborate these results, we also used a series nested linear models to explain the Ct values of the positive tests. This analysis favored a model that included an interaction between age and the late January time period, consistent with the effect of vaccination. We then used demographic data and the daily vaccination rates to estimate the effect of vaccination on viral load reduction. Our estimate suggests that vaccination reduces the viral load by 1.6x to 20x in individuals who are positive for SARS-CoV-2. This estimate might improve after more individuals receive the second dose. Taken together, our findings indicate vaccination is not only important for individual’s protection but can reduce transmission.

Enterocutaneous fistulae (ECF) and enteroatmospheric fistulae (EAF) are difficult complications that primarily arise after abdominal surgical procedures. Development of an ECF or EAF carries significant mortality and morbidity. Effective management of patients with these disease states requires a multidisciplinary approach, which includes surgical, pharmacotherapeutic, and nutritional interventions. This review focuses on the medical and nutritional management of ECF/EAF, providing background on drug agents and nutritional strategies that may be helpful in reducing effluent volume, optimizing fistula healing, and maintaining nutritional health.

BackgroundAccurate medication reconciliation in trauma patients is essential but difficult. Currently there is no established clinical method of detecting direct oral anticoagulants (DOACs) in trauma patients. We hypothesized that a liquid chromatography-mass spectrometry (LCMS) based assay can be used to accurately detect DOACs in trauma patients upon hospital arrival.MethodsPlasma samples were collected from 356 patients who provided informed consent including-10 healthy controls, 19 known positive or negative controls and 327 trauma patients over 65 years of age who were evaluated at our large, urban Level 1 Trauma Center. The assay methodology was developed in healthy and known controls to detect apixaban, rivaroxaban and dabigatran using LCMS and then applied to 327 samples from trauma patients. Standard medication reconciliation processes in the electronic medical record documenting DOAC usage was compared with LCMS results to determine overall accuracy, sensitivity, specificity and positive and negative predictive values (PPV, NPV) of the assay.ResultsOf 356 patients, 39 were on DOACs (10.96%): 21 were on Apixaban, 14 on rivaroxaban and 4 on dabigatran. The overall accuracy of the assay for detecting any DOAC was 98.60%, with a sensitivity of 94.87% and specificity of 99.06%, (PPV 92.50% and NPV 99.37%). The assay detected apixaban with a sensitivity of 90.48% and specificity of 99.11% (PPV 86.36% and NPV 99.40%). There were three false positive results and two false negative LCMS results for apixaban. Dabigatran and rivaroxaban were detected with 100% sensitivity and specificity.ConclusionsThis LCMS-based assay was highly accurate in detecting DOACs in trauma patients. Further studies need to confirm the clinical efficacy of this LCMS assay and its value for medication reconciliation in trauma patients.Study type: diagnostic testBasic Science paper: therefore does not require a level of evidence.

Traumatic injuries to the abdominal cavity are not uncommon trauma. Traumatic injuries requiring surgery mandate a consistent and reproducible entry into the abdominal cavity. This chapter will provide a sound and reproducible approach to the abdomen.

Interleukin-6 (IL-6) is a pleotropic cytokine that signals through the membrane-bound IL-6 receptor (mIL-6R) to induce antiinflammatory(‘‘classic-signaling’’) responses. This cytokine also binds to the soluble IL-6R (sIL-6R) to promote inflammation(‘‘trans-signaling’’). mIL-6R expression is restricted to hepatocytes and immune cells. Activated T cells release sIL-6R into adjacenttissues to induce trans-signaling. These cellular actions require the ubiquitously expressed membrane receptor gp130. Reportsshow that IL-6 is produced by pulmonary arterial smooth muscle cells (PASMCs) exposed to hypoxia in culture as well as themedial layer of the pulmonary arteries in mice exposed to chronic hypoxia (CH), and IL-6 knockout mice are protected from CHinducedpulmonary hypertension (PH). IL-6 has the potential to contribute to a broad array of downstream effects, such as cellgrowth and migration. CH-induced PH is associated with increased proliferation and migration of PASMCs to previously nonmuscularizedvessels of the lung. We tested the hypothesis that IL-6 trans-signaling contributes to CH-induced PH and arterialremodeling. Plasma levels of sgp130 were significantly decreased in mice exposed to CH (380 mmHg) for five days compared tonormoxic control mice (630 mmHg), while sIL-6R levels were unchanged. Consistent with our hypothesis, mice that received theIL-6 trans-signaling-specific inhibitor sgp130Fc, a fusion protein of the soluble extracellular portion of gp130 with the constantportion of the mouse IgG1 antibody, showed attenuation of CH-induced increases in right ventricular systolic pressure, rightventricular and pulmonary arterial remodeling as compared to vehicle (saline)-treated control mice. In addition, PASMCs culturedin the presence of IL-6 and sIL-6R showed enhanced migration but not proliferation compared to those treated with IL-6 or sIL-6Ralone or in the presence of sgp130Fc. These results indicate that IL-6 trans-signaling contributes to pulmonary arterial cellmigration and CH-induced PH.

Damage control surgery (DCS) was developed to manage exsanguinating trauma patients, but is increasingly applied to the management of peritoneal sepsis and abdominal catastrophes. Few manuscripts compare the outcomes of these surgeries on disparate patient populations. A multi-institutional three group propensity score matched case cohort study comparing penetrating trauma (PT-DCS), blunt trauma (BT-DCS), and intraperitoneal sepsis (IPS-DCS) was performed comparing patients treated with DSC between 2008 and 2013. Propensity scoring was performed using demographic and presenting physiologic data. Four hundred and twelve patients were treated with DCS across two institutions. Propensity matching for age, gender, and initial Acute Physiology and Chronic Health Evaluation II score 80 identified 80 patients per group for comparison. Rate of primary fascial closure was lowest in the IPS-DCS group, and highest in the penetrating trauma DCS group. Intra-abdominal complication rates were highest in the IPS-DCS group. IPS-DCS had increased time to definitive closure compared with the other two groups (RR 1.8; 1.3–2.2; P < 0.03). Mortality at 90 days was highest in the IPS-DCS group and patients whose definitive closure was delayed >eight days were more than twice the risk of death at 90 days across all groups. (RR 2.15; 1.2–3.5; P < 0.002). Expected outcomes after the use of DCS for trauma and emergency general surgery are quite different. Despite this difference, prompt abdominal closure at the earliest possible opportunity afforded the best outcome in patients managed via DCS.

Hypoxic pulmonary hypertension (PH) is a progressive and often fatal consequence of chronic hypoxia (CH) exposure (chronic lung diseases, high altitude and sleep apnea). We recently demonstrated that T helper 17 (T H 17) cells are localized in the perivascular region of pulmonary arteries and contribute to CH-induced PH, at least in part, by causing pulmonary arterial (PA) remodeling. Naturally occurring “nT H 17” cells, can be detected as early as week 17 of fetal life in humans, and are in homeostatic equilibrium with natural T regulatory (nTregs) cells. nT H 17 cells are specific for a limited range of self-antigens, including type V collagen (colV). ColV is normally sequestered within type I col in the extracellular matrix of the lungs hidden from the immune system. Activation of matrix metalloproteinase-2, which is induced by CH, can expose colV. Therefore, we tested the hypothesis that ColV is a lung-associated self-antigen uncovered by CH. We found colV immunoreactivity only in lungs from mice exposed to hypobaric CH for 5 days vs. controls and colV mRNA expression is significantly increased in isolated PA (log fold change mean±SEM, normoxia= 0.22±0.08 vs. CH=0.48±0.02, n=3, p=0.02) suggesting that CH uncovers hidden colV. We then, determined cellular autoimmunity to colV using a trans-vivo delayed-type hypersensitivity assay (TV-DTH). Splenocytes obtained from 5 days CH-exposed mice displayed a TV-DTH colV response significantly higher than that from normoxic mice (footpad swelling [10 -4 ”] normoxia=11.8±1.1 vs. CH= 35.6±3.0, n=14, p=0.0001), while there was minimal response to col I. To determine that reactivity to colV contributes to CH-induced PH, we induced peripheral tolerance to colV by administering 25 μl of 0.08 μg/μl of bovine colV (Sigma) in PBS in each nare or PBS every two days for two weeks prior and during CH (21 days). Right ventricular systolic pressure (RVSP) was higher in vehicle-treated compared to colV-treated mice (mmHg CH vehicle= 32.4±0.3 vs. CH colV= 27.8±0.9, n=4, p=0.0085) suggesting that oral tolerance to col V attenuated PH. These results are ground-breaking suggesting that acute autoreactivity to colV develops after exposure to hypoxia. Next, we will determine whether a disrupted balance of nTh17/nTreg mediates this response.

Purpose Results of an initiative at an academic medical center to reduce prescription opioid use in patients with acute traumatic injuries are reported. Methods In 2014, the University of Kentucky Hospital trauma service implemented a pain management strategy consisting of patient and provider education emphasizing the use of nonopioid analgesics to minimize opioid use without compromising analgesia effectiveness. To assess the impact of the initiative, a retrospective analysis of data on cohorts of patients admitted with acute trauma before ( n = 489) and after ( n = 424) project implementation was conducted. The primary endpoint was opioid use (prescribed daily milligram morphine equivalents [MME]) at discharge. Secondary endpoints included inpatient opioid and alternative analgesic use, pain control, ileus development, length of stay, and discharge disposition. Results Compared with the preintervention cohort, the postintervention cohort had a lower median daily discharge MME overall (45 MME versus 90 MME, p Conclusion Targeted provider and patient education on minimizing opioid use was associated with a reduction in MME on discharge from the hospital after traumatic injury.

Transfusion-related immunomodulation consists of both proinflammatory and anti-inflammatory responses after transfusion of blood products. Stored red blood cells (RBCs) suppress human T-cell proliferation in vitro, but the mechanism remains unknown. We hypothesized that cytokine synthesis by T cells may be inhibited when stored RBCs are present and that suppression between fresh and stored RBCs would be different.Purified human T cells were stimulated to proliferate with anti-CD3/anti-CD28 and then exposed to stored or fresh RBCs. Cells were placed in culture for 5 days. Cell culture supernatants were analyzed for the production of typical T-cell cytokines using multianalyte ELISArray kits.Stimulated T cells proliferated. RBC exposure markedly suppressed this proliferation. Interleukin 10, interleukin 17a, interferon γ, tumor necrosis factor α, and granulocyte macrophage colony-stimulating factor were increased in response to stimulation but depressed in the presence of stored RBCs. The use of fresh RBCs also resulted in depression of these cytokines when compared with stimulated T cells with no RBCs; however, this depression was less pronounced.T-cell activation is associated with both proinflammatory and anti-inflammatory cytokine release, comparable with patterns seen in trauma and acute injury. All of these responses are depressed by an exposure to stored RBCs. Decreased levels of these cytokines after RBC transfusion represents a potential contributor to the immunosuppressive complications seen in trauma patients after transfusion. This provides insight for future mechanistic studies to delineate the role of RBC transfusion in transfusion-related immunomodulation.

We describe the expansion of a publicly available archive of downscaled climate and hydrology projections for the United States. Those studying or planning to adapt to future climate impacts demand downscaled climate model output for local or regional use. The archive we describe attempts to fulfill this need by providing data in several formats, selectable to meet user needs. Our archive has served as a resource for climate impacts modelers, water managers, educators, and others. Over 1,400 individuals have transferred more than 50 TB of data from the archive. In response to user demands, the archive has expanded from monthly downscaled data to include daily data to facilitate investigations of phenomena sensitive to daily to monthly temperature and precipitation, including extremes in these quantities. New developments include downscaled output from the new Coupled Model Intercomparison Project phase 5 (CMIP5) climate model simulations at both the monthly and daily time scales, as well as simulations of...

Inflammation is a prominent pathological feature in pulmonary arterial hypertension, as demonstrated by pulmonary vascular infiltration of inflammatory cells, including T and B lymphocytes. However, the contribution of the adaptive immune system is not well characterized in pulmonary hypertension caused by chronic hypoxia. CD4+ T cells are required for initiating and maintaining inflammation, suggesting that these cells could play an important role in the pathogenesis of hypoxic pulmonary hypertension. Our objective was to test the hypothesis that CD4+ T cells, specifically the T helper 17 subset, contribute to chronic hypoxia-induced pulmonary hypertension. We compared indices of pulmonary hypertension resulting from chronic hypoxia (3 wk) in wild-type mice and recombination–activating gene 1 knockout mice (RAG1−/−, lacking mature T and B cells). Separate sets of mice were adoptively transferred with CD4+, CD8+, or T helper 17 cells before normoxic or chronic hypoxic exposure to evaluate the involvement of specific T cell subsets. RAG1−/− mice had diminished right ventricular systolic pressure and arterial remodeling compared with wild-type mice exposed to chronic hypoxia. Adoptive transfer of CD4+ but not CD8+ T cells restored the hypertensive phenotype in RAG1−/− mice. Interestingly, RAG1−/− mice receiving T helper 17 cells displayed evidence of pulmonary hypertension independent of chronic hypoxia. Supporting our hypothesis, depletion of CD4+ cells or treatment with SR1001, an inhibitor of T helper 17 cell development, prevented increased pressure and remodeling responses to chronic hypoxia. We conclude that T helper 17 cells play a key role in the development of chronic hypoxia-induced pulmonary hypertension.

The high climate sensitivity of hydrologic systems, the importance of those systems to society, and the imprecise nature of future climate projections all motivate interest in characterizing uncertainty in the hydrologic impacts of climate change. We discuss recent research that exposes important sources of uncertainty that are commonly neglected by the water management community, especially, uncertainties associated with internal climate system variability, and hydrologic modeling. We also discuss research exposing several issues with widely used climate downscaling methods. We propose that progress can be made following parallel paths: first, by explicitly characterizing the uncertainties throughout the modeling process (rather than using an ad hoc “ensemble of opportunity”) and second, by reducing uncertainties through developing criteria for excluding poor methods/models, as well as with targeted research to improve modeling capabilities. We argue that such research to reveal, reduce, and represent uncertainties is essential to establish a defensible range of quantitative hydrologic storylines of climate change impacts.

The emergency care of ventral hernias is complex. The key to improved morbidity and mortality is operating on these patients prior to progressing to strangulation. The type of operation depends on many factors, including location of the hernia, patient’s physiology, imaging findings, and prior repairs with or without mesh. The operations can be open, laparoscopic, or a combination of both. The use of laparoscopy has a significant role in assessing bowel viability and repair. Dealing with large ventral hernias in a damage control surgery should focus on sepsis source control and abdominal closure. In these patients, definitive and complex abdominal wall closures with non-biologic prosthesis should be avoided. The goal is survival and planning a formal abdominal wall construction in the future with a non-biologic prosthesis. This chapter will review these topics.

Surgical resident rotations on trauma services are criticized for little operative experience and heavy workloads. This has resulted in diminished interest in trauma surgery among surgical residents. Acute care surgery (ACS) combines trauma and emergency/elective general surgery, enhancing operative volume and balancing operative and nonoperative effort. We hypothesize that a mature ACS service provides significant operative experience.A retrospective review was performed of ACGME case logs of 14 graduates from a major, academic, Level I trauma center program during a 3-year period. Residency Review Committee index case volumes during the fourth and fifth years of postgraduate training (PGY-4 and PGY-5) ACS rotations were compared with other service rotations: in total and per resident week on service.Ten thousand six hundred fifty-four cases were analyzed for 14 graduates. Mean cases per resident was 432 ± 57 in PGY-4, 330 ± 40 in PGY-5, and 761 ± 67 for both years combined. Mean case volume on ACS for both years was 273 ± 44, which represented 35.8% (273 of 761) of the total experience and exceeded all other services. Residents averaged 8.9 cases per week on the ACS service, which exceeded all other services except private general surgery, gastrointestinal/minimally invasive surgery, and pediatric surgery rotations. Disproportionately more head/neck, small and large intestine, gastric, spleen, laparotomy, and hernia cases occurred on ACS than on other services.Residents gain a large operative experience on ACS. An ACS model is viable in training, provides valuable operative experience, and should not be considered a drain on resident effort. Valuable ACS rotation experiences as a resident may encourage graduates to pursue ACS as a career.

The existence of tumor-specific T cells, as well as their ability to be primed in cancer patients confirms that the immune response can be deployed to combat cancer. However, there are obstacles that must be overcome to convert the ineffective immune response commonly found in the tumor environment to one that leads to sustained destruction of tumor. Members of the tumor necrosis factor (TNF) superfamily direct diverse immune functions. OX40 and its ligand, OX40L, are key TNF members that augment T-cell expansion, cytokine production, and survival. OX40 signaling also controls regulatory T cell differentiation and suppressive function. Studies over the past decade have demonstrated that OX40 agonists enhance anti-tumor immunity in preclinical models using immunogenic tumors; however, treatment of poorly immunogenic tumors has been less successful. Combining strategies that prime tumor-specific T cells together with OX40 signaling could generate and maintain a therapeutic anti-tumor immune response.

Despite the prevalence of acute pain in the trauma setting and known complications of its improper management, including risk of chronic pain, delayed recovery, and poorer quality of life, recent survey data suggest little has changed in the overall management of pain in the acute setting during the

PURPOSE A randomized controlled trial study was performed to evaluate the efficacy of transcutaneous tibial nerve stimulation (TTNS) and sham TTNS, in patients with Parkinson disease (PD) with lower urinary tract symptoms (LUTS). DESIGN Randomized controlled trial. SUBJECTS AND SETTINGS Thirteen patients with a diagnosis of PD and bothersome LUTS were randomly allocated to one of the following groups: Group I: TTNS group (n = 8) and group II: Sham group (n = 5). Both groups attended twice a week during 5 weeks; each session lasted 30 minutes. METHODS Eight patients received TTNS treatment and 5 subjects allocated to group II were managed with sham surface electrodes that delivered no electrical stimulation. Assessments were performed before and after the treatment; they included a 3-day bladder diary, Overactive Bladder Questionnaire (OAB-V8), and the International Consultation on Incontinence Quality of Life Questionnaire Short Form (ICIQ-SF), and urodynamic evaluation. RESULTS Following 5 weeks of treatment, patients allocated to TTNS demonstrated statistically significant reductions in the number of urgency episodes (P = .004) and reductions in nocturia episodes (P < .01). Participants allocated to active treatment also showed better results after treatment in the OAB-V8 and ICIQ-SF scores (P < .01, respectively). Urodynamic testing revealed that patients in the active treatment group showed improvements in intravesical volume at strong desire to void (P < .05) and volume at urgency (P < .01) when compared to subjects in the sham treatment group. CONCLUSION These findings suggest that TTNS is effective in the treatment of LUTS in patients with PD, reducing urgency and nocturia episodes and improving urodynamic parameters as well as symptom scores measured by the OAB-V8 and health-related quality-of-life scores measured by the ICIQ-SF.

A climate change impacts assessment for water resources in the San Joaquin River region of California is presented. Regional climate projections are based on a 1 percent per year CO 2 increase relative to late 20th Century CO 2 conditions. Two global projections of this CO 2 increase scenario are considered (HadCM2 and PCM) during two future periods (2010 to 2039 and 2050 to 2079). HadCM2 projects faster warming than PCM. HadCM2 and PCM project wetter and drier conditions, respectively, relative to present climate. In the HadCM2 case, there would be increased reservoir inflows, increased storage limited by existing capacity, and increased releases for deliveries and river flows. In the PCM case, there would be decreased reservoir inflows, decreased storage and releases, and decreased deliveries. Impacts under either projection case cannot be regarded as more likely than the other. Most of the impacts uncertainty is attributable to the divergence in the precipitation projections. The range of assessed impacts is too broad to guide selection of mitigation projects. Regional planning agencies can respond by developing contingency strategies for these cases and applying the methodology herein to evaluate a broader set of CO 2 scenarios, land use projections, and operational assumptions. Improved agency access to climate projection information is necessary to support this effort.

Using a genome-scale, lentivirally delivered shRNA library, we performed massively parallel pooled shRNA screens in 216 cancer cell lines to identify genes that are required for cell proliferation and/or viability. Cell line dependencies on 11,000 genes were interrogated by 5 shRNAs per gene. The proliferation effect of each shRNA in each cell line was assessed by transducing a population of 11M cells with one shRNA-virus per cell and determining the relative enrichment or depletion of each of the 54,000 shRNAs after 16 population doublings using Next Generation Sequencing. All the cell lines were screened using standardized conditions to best assess differential genetic dependencies across cell lines. When combined with genomic characterization of these cell lines, this dataset facilitates the linkage of genetic dependencies with specific cellular contexts (e.g., gene mutations or cell lineage). To enable such comparisons, we developed and provided a bioinformatics tool to identify linear and nonlinear correlations between these features.

We have demonstrated that the adaptive immune system along with nuclear factor of activated T cells isoform c3 (NFATc3) contribute to chronic hypoxia (CH)-induced pulmonary hypertension (PH). NFATc...

We have previously demonstrated that adaptive immune cells contribute to chronic hypoxia (CH)-induced pulmonary hypertension (PH). Within the adaptive immune system, CD4+ T cells are required for i...

This collaborative research project has two main objectives: to assess the vulnerability of water supply, water demand, water quality, ecosystem health and socioeconomic welfare within the San Joaquin River Basin as a function of climate variability and extreme weather events; and to provide guidance in the formulation of effective management strategies to mitigate the range of potential impacts due to climate variability and extreme weather. The project involves updating and advancing previous studies on climate change in California. Climate data are based on new Global Circulation Model output from the statistical downscaling that converts GCM climate forecasts into local weather forecasts. The project applies these climate data to perturb an existing 72-year historical hydrologic time series of the San Joaquin Basin to develop an integrated impacts analysis of climate change/variability on the water, economic and social resources of the Basin. Previous studies focused only on water resource impacts. A decision support system (DSS) is under development that will provide assistance to CALFED (a joint California State and Federal program designed to resolve water issues in the Bay–Delta) in water resource and ecosystem management of the San Joaquin Basin.

This chapter summarizes the scope of what is known and not known about climate in the Southwestern United States. There is now more evidence and more agreement among climate scientists about the physical climate and related impacts in the Southwest compared with that represented in the 2009 National Climate Assessment (Karl, Melillo and Peterson 2009). However, there remain uncertainties about the climate system, the complexities within climate models, the related impacts to the biophysical environment, and the use of climate information in decision making.

This chapter examines research strategies that aim to reduce uncertainty associated with climate drivers and their effects on systems in the Southwest. It also identifies scientific approaches that are being considered for implementation in programs of adaptive responses to climate change. This chapter was written collaboratively with Chapter 19, which outlines some of the most important uncertainties related to climate variability and change in the Southwestern United States. In these chapters the uncertainty derives from both our presently imperfect capability to model climate and other earth systems and from our inability to adequately characterize social, economic, policy and regulatory responses in the form of adaptation and mitigation.

Acute care surgery (ACS) includes trauma, surgical critical care, and emergent general surgery. There is a national shortage of institutions that can provide for patients needing access to emergency surgical care. Inability to fund ACS surgeons can be a barrier. We hypothesize that an ACS service, in an appropriately staffed hospital, generates a positive contribution margin (CM).Fiscal data for 2009 were retrospectively reviewed at the University of Kentucky, a Level I trauma center with an ACS service. Contribution margin (ie, net revenue minus direct costs) and mean length of stay were calculated for all patients admitted to the ACS service. Inpatient data were stratified by trauma vs general surgery, emergent vs elective, and by payor mix.Annual CM associated with the 5 ACS faculty was $21,799,000. Trauma generated higher CM than general surgery. General surgery had a greater CM, more if emergent than if elective ($9,500 vs $5,500; p0.01). Self-payment was lower with emergent general surgery vs trauma (20% vs 25%; p = 0.02).Acute care surgery generates a positive CM. Emergent general surgery generates a greater CM than elective general surgery because of increased case mix index. These data suggest that hospital subsidization of acute care surgeons is financially feasible and might address the surgical workforce shortage and the critical problem of access to emergency surgical services.

The magnitude of climate change impacts facing water resources managers in the United States has spurred closer interagency cooperation in developing methods supporting planning and engineering for climate change adaptation. The two largest water resources management agencies in the U.S., the U.S. Army Corps of Engineers and the Bureau of Reclamation, have partnered to describe climate change challenges, identify user needs for improving tools and information, and assess capabilities to use weather and climate forecasts in federal water resources management. They have also hosted a forum with national and international experts exploring the issue of nonstationary hydrology with respect to climate change. In progress is development of multiagency guidelines for best practices to select from the portfolio of climate information including global climate scenarios, through general circulation models, through downscaling, to regional or watershed-scale hydrological and operations planning models to account properly for climate change and variability at the scale of water-resource operational decisions. This presentation describes collaborative activities and the resulting methods being used as both agencies plan for and implement climate change adaptation measures.

The steady march of Moore's law demands ever smaller feature sizes to be printed and Optical Proximity Correction to correct to ever tighter dimensional tolerances. Recently pitch doubling techniques has relieved the pressure on CD reduction, which instead of being achieved lithographically are reduced by subsequent etching or chemical interaction with spin-on layers. CD tolerance reductions, however, still need to match the overall design rule shrinkage. The move to immersion lithography, where effective Numerical Apertures now reach 1.35, has been accompanied by a significantly reduction in depth of focus, especially on isolated contacts. To remedy this, RET techniques such as assist feature placement, have been implemented. Certain local placements of assist features and neighboring contacts are observed to result in highly elliptical contacts being printed. In some layouts small changes in the aspect ratio of the contact on the mask leads to strong changes in the aspect ratio of the printed contact, whereas in other layouts the response is very weak. This effect can be described as an aspect ratio MEEF. The latter type of contact can pose a significant challenge to the OPC recipe which is driven by the need to place the printed contour within a small range of distance from target points placed on the midpoint of edges of a nominally square contact. The OPC challenge naturally will be compounded when the target layout is rectangular in the opposite sense to the natural elliptical shape of the printed contact. Approaches to solving this can vary from intervening at the assist feature placement stage, at the possible loss of depth of focus, to accepting a certain degree of ellipticity in the final contour and making the OPC recipe concentrate on minimizing any residual errors. This paper investigates which contact layouts are most challenging, discusses the compromises associated with achieving the correction target and results are shown from a few different approaches to resolving these issues.

INTRODUCTION Laparoscopic inguinal hernia repair can be performed totally extraperitoneal or transabdominal preperitoneal (TAPP). Both repairs are associated with mesh-related complications. This is the first report of a mesh-strangulated appendix, with subsequent necrosis and perforation, after TAPP inguinal hernia repair. CASE A 48-year-old male, 10-years status post-bilateral TAPP inguinal hernia repair presented with acute right groin bulge, pain, nausea, emesis, and fever. He was found to have a large, tender, nonreducible right groin mass. He was taken to the operating room for right groin exploration and found to have gross purulent material but no evidence of a recurrent hernia. A laparoscope was inserted into the abdomen where the appendix was found strangulated between the mesh and the transversalis fascia. CONCLUSIONS Mesh-related complications after TAPP inguinal hernia repair are rare. This is the first report of a strangulated appendix secondary to mesh entrapment after TAPP repair.

Studies of specific procedures have shown increases in infectious complications with operative duration. We hypothesized that operative duration is independently associated with increased risk-adjusted infectious complication (IC) rates in a broad range of general surgical procedures.We queried the American College of Surgeons National Surgical Quality Improvement Program database for general surgical operations performed from 2005 to 2007. ICs (wound infection, sepsis, urinary tract infection, and/or pneumonia) and length of hospital stay (LOS) were evaluated versus operative duration (OD, ie, incision to closure). Multivariable regression adjusted for 38 patient risk variables, operation type and complexity, wound class and intraoperative transfusion. We also analyzed isolated laparoscopic cholecystectomies in patients of American Society of Anesthesiologists class 1 or 2, without intraoperative transfusion and with a clean or clean-contaminated wound class.In 299,359 operations performed at 173 hospitals, unadjusted IC rates increased linearly with OD at a rate of close to 2.5% per half hour (chi-square test for linear trend, p0.001). After adjustment, IC risk increased for each half hour of OD relative to cases lastingor=1 hour, almost doubling at 2.1 to 2.5 hours (odds ratio = 1.92; 95% CI, 1.82 to 2.03; p0.001). In isolated laparoscopic cholecystectomy, IC rates increased linearly with OD (n = 17,018, chi-square test for linear trend, p0.001) with rates for 1.1 to 1.5 hour cases (1.4%) doubling those lastingor=0.5 hour (0.7%). Across all procedures, adjusted LOS increased geometrically with operative duration at a rate of about 6% per half hour (coefficient for natural log transformed LOS = 0.059 per half hour; 95% CI, 0.058 to 0.060; p0.001).Operative duration is independently associated with increased ICs and LOS after adjustment for procedure and patient risk factors.

A challenge in model-based assist feature placement is to find optimal placements while satisfying mask rules and preventing AF printing. There are numerous strategies for achieving this ranging from fully rule-based methods to pixel-based inversion. Our proposed solution is to identify the optimal locations of assist features using modeling information based strictly on optics and resist stack optical characteristics. Once these positions have been found, preliminary AFs can be placed. At this point suggested sizes and shapes can be identified, although these can later be modified. In a later step, MRC cleanup, printability fixing, and main-pattern OPC can be performed simultaneously. This has the advantage of allowing the use of the full process model to predict the location of OPC edges accurately, and use calibrated or 3d mask models to determine assist feature printing behavior. This correction is done while maintaining MRC constraints. In this flow, an AF placement field, generated from the pre-OPC target patterns, can be used to provide accurate guidance on how to move assist features to get the most benefit while keeping other constraints in mind. Using this method, a range of printability fixing strategies, guided by placement benefits, is available. We present data showing that the benefit of AF placements can be determined from optical parameters, on target (non-OPC) data, and that this method leads to beneficial yet compliant masks.

Double Patterning is seen as the prime technology to keep Moore’s law on path while EUV technology is still maturing into production worthiness. As previously seen for alternating-Phase Shift Mask technology[1], layout compliance of double patterning is not trivial [2,3] and blind shrinks of anything but the most simplistic existing layouts, will not be directly suitable for double patterning. Evaluating a production worthy double patterning engine with highly non-compliant layouts would put unrealistic expectations on that engine and provide metrics with poor applicability for eventual large designs. The true production use-case would be for designs that have at least some significant double patterning compliance already enforced at the design stage. With this in mind a set of ASIC design blocks of different sizes and complexities were created that were double patterning compliant. To achieve this, a set of standard cells were generated, which individually and in isolation were double patterning compliant, for multiple layers simultaneously. This was done using the automated Standa rd Cell creation tool Cadabr a™ [4]. To create a full ASIC, however, additional constraints were added to make sure compliance would not be broken across the boundaries between standard cells when placed next to each other [5]. These standard cells were then used to create a variety of double patterning compliant ASICs using iCCompiler™ to place the cells correctly. Now with a compliant layout, checks were made to see if the constraints made at the micro level really do ensure a fully compliant layout on the whole chip and if the coloring engine could cope with such large datasets. A production worthy double patterning engine is ideally distributable over multiple processors [6,7] so that fast turn-around time can be achievable on even the largest designs. We demonstrate the degree of linearity of scaling achievab le with our double patterning engine. These results can be understood together with metrics such as the distribution of the sizes of networks requiring coloring resulting from these designs.

Hernia is derived from the Latin word meaning “rupture or protrusion”. A hernia is the protrusion of tissue or an organ through a defect or weakness in the surrounding walls. Abdominal wall hernias occur at sites lacking a covering with overlapping aponeuroses and fascia. Hernias can be present at birth (congenital), develop spontaneously over time or as a result of surgery or trauma. Areas on the ventral abdominal wall prone to hernia formation are located at the arcuate line, epigastric, inguinal and umbilical hernias. Iatrogenic hernias on the abdominal wall occur at sites of surgical incisions (incisional hernias).

Some embodiments provide techniques and systems to identify locations in a target mask layout for placing assist features. During operation, an embodiment can determine a spatial sampling frequency to sample the target mask layout, wherein sampling the target mask layout at the spatial sampling frequency prevents spatial aliasing in a gradient of a cost function which is used for computing an inverse mask field. Next, the system can generate a grayscale image by sampling the target mask layout at the spatial sampling frequency. The system can then compute the inverse mask field by iteratively modifying the grayscale image. The system can use the gradient of the cost function to guide the iterative modification process. Next, the system can filter the inverse mask field using a morphological operator, and use the filtered inverse mask field to identify assist feature locations in the target mask layout.

Double patterning has gained prominence as the most likely lithographic methodology to help keep Moore's law going towards 32nm 1/2 pitch lithography. While solutions, to date, have focused mainly on gap splitting to avoid minimum spacing violations, the decomposition should, ideally, also attempt to optimize the process window of the decomposed masks. A major contributor to process window sensitivity is the correct placement of sub-resolvable assist features. These features are placed once the polygons of each mask are defined, i.e. post decomposition. If some awareness of this downstream process step is made available to the double patterning decomposition stage, then a more robust decomposition can be achieved.

Due to shrinking design nodes and to some limitations of scanners, extreme off-axis illumination (OAI) required and its use and implementation of assist features (AF) to solve depth of focus (DOF) problems for isolated features and specific pitch regions is essential. But unfortunately, the strong periodic character of OAI illumination makes AF's print more easily. Present OPC flows generate AFs before OPC, which is also causes some AF printing problems. At present, mask manufacturers must downsize AF's below 30nm to solve this problem. This is challenging and increases mask cost. We report on an AF-fixer tool which is able to check AF printability and correct weak points with minimal cost in terms of DOF after OPC. We have devised an effective algorithm that removes printing AF's. It can not only search for the best non-printing AF condition to meet the DOF spec, but also reports uncorrectable spots, which could be marked as design errors. To limit correction times and to maximize DOF in full-chip correction, a process window (PW) model and incremental OPC method are applied. This AF fixer, which suggests optimum AF in only weak point region, solves AF printing problems economically and accurately.

Double patterning technology (DPT) is one of the main options for printing logic devices with half-pitch less than 45nm; and flash and DRAM memory devices with half-pitch less than 40nm. DPT methods decompose the original design intent into two individual masking layers which are each patterned using single exposures and existing 193nm lithography tools. The results of the individual patterning layers combine to re-create the design intent pattern on the wafer. In this paper we study interactions of DPT with lithography, masks synthesis and physical design flows. Double exposure and etch patterning steps create complexity for both process and design flows. DPT decomposition is a critical software step which will be performed in physical design and also in mask synthesis. Decomposition includes cutting (splitting) of original design intent polygons into multiple polygons where required; and coloring of the resulting polygons. We evaluate the ability to meet key physical design goals such as: reduce circuit area; minimize rework; ensure DPT compliance; guarantee patterning robustness on individual layer targets; ensure symmetric wafer results; and create uniform wafer density for the individual patterning layers.

Demanding process window constraints have increased the need for effective assist feature placement algorithms that are robust and flexible. These algorithms must also allow for quick ramp up when changing nodes or illumination conditions. Placement based on the optical components of real process models has the potential to satisfy all of these requirements. We present enhancements to model-based assist feature algorithms. These enhancements include exploration of image-processing techniques that can be exploited for contact-via AF placement, model-based mask rule check (MRC) conflict resolution, the application of models to line-space patterns, and a novel placement technique for contact-via layers using a specially-built single modeling kernel.

The upcoming 45nm and 32nm device generations will continue the familiar industry lithography trends of decreased production K1 factor, reduced focus error tolerances and increased pattern density. As previous experience has shown, small changes in the values of lithographic K1, focus tolerance and pattern density for the process-design space can lead to large required changes in OPC and RET solutions. Therefore, significant improvements in utility and speed are needed for these new device generations. In this paper we highlight significant new functionality and performance capabilities using existing Field-based OPC and RET methods. The use of dense grid calculations in Field-based methods is shown to provide a software platform for robust and fast implementation of new model-based RET techniques such as model-based assist feature placement and tuning. We present the performance and capability increases for model-based RET methods. Additionally, we have studied and present the performance of production 45nm generation field-based OPC and RET software across several different multiple-purpose hardware platforms. Significant improvements in runtime (for approximately the same hardware cost) are observed with new general purpose hardware platforms and with software optimization for this hardware.

Sub-resolution assist features (SRAFs) are an important tool for improving through-process robustness of advanced lithographic processes. Assist features have generally been placed and adjusted according to heuristic rules. The complexity of these rules increases rapidly with shrinking features size requiring more wafer data for calibration and more effort on the part of engineers. For advanced nodes, a model-based approach may better account for the variety of two-dimensional geometries and reduce substantially the amount of user effort required for effective SRAF placement. There are many ways in which model-based methods can be used to improve the effectiveness of assist features; we investigate several here. In the investigations described here, process window models may be employed to: 1) derive optimal rules for initial AF placement in a rule-based process, 2) resolve mask rule violations in optimal ways, and 3) make post-placement corrections of mask sites with poor behavior. In addition, we discuss a method for replacing an initial rule-based assist feature placement with a model-based placement which can consider the local two-dimensional geometry.

Sub-resolution assist features are an important tool for improving process robustness for one-dimensional pattern features at advanced manufacturing process nodes. However, sub-resolution assist feature development efforts have not generally considered optimization for process robustness with two-dimensional pattern features. This generally arises both from conservatively placing SRAFs to avoid the possibility of imaging, and from a desire to simplify SRAF placement rules. By studying two-dimensional features using a manufacturing sensitivity model, one can gain insight into the capabilities of SRAFs regarding two-dimensional pattern features. These insights suggest new methodologies for shaping assist features to enhance two-dimensional feature robustness. In addition, a manufacturing sensitivity model form can be employed to optimize the placement of multiple competing SRAFs in localized two-dimensional regions. Initial studies demonstrate significant pullback reduction for two-dimensional features once SRAF placement has been optimized using the manufacturing sensitivity model form.

Climate change is an important and well-studied phenomenon and historical data tracking changes in weather and climate are readily available. Climate change could induce shifts in mean values for weather variables and/or cause new patterns in climate variability, both of which could cause impacts on water demands, supplies, and source water quality. Water suppliers are beginning to consider the potential impacts of climate change on future water supplies. However, the focus of past work has been on water quantity impacts (e.g., flooding and droughts) rather than on changes in water quality. This paper focuses on an assessment of how various climate change scenarios would affect lake hydrology and selected source water quality parameters for Lake Cachuma, which provides water supply to the Goleta Water District and several other water agencies in Santa Barbara County, California. The climate change assessment indicates that under a variety of scenarios of a warming climate, the likelihood of taste and odor events during the dry season would increase and turbidity and apparent color events would be more likely if precipitation rates increase.

In psychiatry, individual‐based registries have provided key information on risks and benefits associated with the use of psychotropic drugs but they have rarely been employed for monitoring and evaluating the everyday prescribing of psychopharmacological treatments. This article describes the cultural background that gave impetus to the idea of registering all prescriptions of psychotropic drugs dispensed by physicians working in the South Verona community mental health service, and presents the methodology employed to develop such a registry in a community psychiatric service where a psychiatric case register (PCR) has been operating since 1978. We developed a registry including every patient receiving psychotropic medications in ordinary practice. This registry is linked to the PCR in order to obtain data on social and demographic characteristics, clinical symptoms, diagnosis, use of services, and outcomes. No exclusion criteria are allowed — anyone receiving treatment is automatically included. This system, which can link drug and service‐use data with hard outcome indicators, can generate information on the proportion of subjects discontinuing treatment, switching medication because of side‐effects, recovery or inefficacy, as well as on the proportion of subjects failing to return to the physician, and the proportion of patients who improve. The innovative aspect of this approach is that this registry is developed, organized and used by physicians interested in monitoring their clinical practice and in providing patients, relatives and the public with accurate information on drug use in their specific context of care. Copyright © 2005 John Wiley & Sons, Ltd.

The US National Assessment of the Potential Consequences of Climate Variability and Change provides compelling arguments for action and adaptive measures to help mitigate water resource, agricultural production and environmental quality impacts of future climate change. National resource planning at this scale can benefit by the development of integrated impact analysis toolboxes that allow linkage and integration of hydroclimate models, surface and groundwater hydrologic models, economic and environmental impact models and techniques for social impact assessment. Simulation models used in an assessment of climate change impacts on water resources, agriculture and environmental quality in the San Joaquin Basin of California are described in this paper as well as the challenges faced in linking the component models within an impacts assessment toolbox. Results from simulations performed with several of the tools in the impacts assessment toolbox are presented and discussed. After initially attempting model integration with the public domain, GIS-based modeling framework Modular Modeling System/Object User Interface (MMS/OUI), frustration with the framework’s lack of flexibility to handle monthly timestep models prompted development of a common geodatabase to allow linkage of model input and output for the linked simulation models. A GIS-based data browser was also developed that works with both network flow models and makes calls to a model post-processor that shows model output for each selected node in each model network. This data and output browser system is flexible and can readily accommodate future changes in the model network configuration and in the model database. US EPA STAR Program/[R827448-01-0]//Estados Unidos UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones Geofísicas (CIGEFI)