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In tropical regions, widespread loss of native forest and savanna vegetation is increasing extreme heat, particularly in agricultural regions. Using the case of rising extreme heat from lost forest and savanna vegetation in Brazilian Amazon and Cerrado regions, we modeled losses to soy production, the region’s principal economic activity. We assessed two types of extreme-heat regulation values: the value of avoided extreme-heat exposure of soy from the conservation of neighboring ecosystems and the value of lost revenue due to increased extreme heat exposure from increased ecosystem conversion. Our modeling combines empirical estimates of (1) the influence of ecosystem conversion on extreme heat over neighboring cropland, (2) the impacts of extreme heat on agricultural yields, and (3) native vegetation area, agricultural area, and crop prices. We examine lost soy value from land conversion over the period 1985 to 2012, potential losses from further conversion under plausible land and climate change scenarios (2020–2050), and the future value of conservation of the region’s remaining ecosystem area near soy. Soy revenue lost due to extreme heat from native vegetation loss (1985–2012) totaled 99 (2005USD) ha−1 for 2012-2013 growing season. By 2050, agricultural growth, ecosystem conversion, and climate change could boost extreme-heat regulation values by 25% to 95%. Future values were strongly sensitive to changes in agricultural density, rates of native vegetation loss, and climate. Extreme-heat regulation values were largest in the Cerrado biome and the southeastern Amazon. Relative to land values, the value of extreme heat regulation was largest relative to the carbon value of biomass in the Cerrado. By regulating the exposure of agriculture to extreme heat, ecosystem conservation can create considerable value for the soy sector.

Epilepsy is one of the most common diseases of the central nervous system, impacting nearly 50 million people around the world. Heterogeneous in nature, epilepsy presents in children and adults alike. Currently, surgery is one treatment approach that can completely cure epilepsy. However, not all individuals are eligible for surgical procedures or have successful outcomes. In addition to surgical approaches, antiepileptic drugs (AEDs) have also allowed individuals with epilepsy to achieve freedom from seizures. Others have found treatment through nonpharmacologic approaches such as vagus nerve stimulation, or responsive neurostimulation. Difficulty in accessing samples of human brain tissue along with advances in sequencing technology have driven researchers to investigate sampling liquid biopsies in blood, serum, plasma, and cerebrospinal fluid within the context of epilepsy. Liquid biopsies provide minimal or non-invasive sample collection approaches and can be assayed relatively easily across multiple time points, unlike tissue-based sampling. Various efforts have investigated circulating nucleic acids from these samples including microRNAs, cell-free DNA, transfer RNAs, and long non-coding RNAs. Here, we review nucleic acid-based liquid biopsies in epilepsy to improve understanding of etiology, diagnosis, prediction, and therapeutic monitoring.

Alzheimer’s disease is the most common neurodegenerative disease and affects persons of all races, ethnic groups, and sexes. The disease is characterized by neuronal loss leading to cognitive decline and memory loss. There is no cure and the effectiveness of existing treatments is limited and depends on the time of diagnosis. The long prodromal period, during which patients’ ability to live a normal life is not affected despite neuronal loss, often leads to a delayed diagnosis because it can be mistaken for normal aging of the brain. In order to make a substantial impact on AD patients, early diagnosis may provide a greater therapeutic window for future therapies to slow AD-associated neurodegeneration. Current gold standards for disease detection include magnetic resonance imaging and positron emission tomography scans, which visualize amyloid β and phosphorylated tau depositions and aggregates. Liquid biopsies, already an active field of research in precision oncology, are hypothesized to provide early disease detection through minimally or non-invasive sample collection techniques. Liquid biopsies in Alzheimer’s disease have been studied in cerebrospinal fluid, blood, ocular, oral, and olfactory fluids. However, most of the focus has been on blood and cerebrospinal fluid due to biomarker specificity and sensitivity attributed to the effects of the blood-brain barrier and inter-laboratory variation during sample collection. Many studies have identified amyloid β and phosphorylated tau levels as putative biomarkers, however, advances in next-generation sequencing-based liquid biopsy methods have led to significant interest in identifying nucleic acids species associated with Alzheimer’s disease from liquid tissues. Differences in cell-free RNAs and DNAs have been described as potential biomarkers for AD and hold the potential to affect disease diagnosis, treatment, and future research avenues.

Large-scale agriculture in the state of Mato Grosso, Brazil is a major contributor to global food supplies, but its continued productivity is vulnerable to contracting wet seasons and increased exposure to extreme temperatures. Sowing dates serve as an effective adaptation strategy to these climate perturbations. By controlling the weather experienced by crops and influencing the number of successive crops that can be grown in a year, sowing dates can impact both individual crop yields and cropping intensities. Unfortunately, the spatiotemporally resolved crop phenology data necessary to understand sowing dates and their relationship to crop yield are only available over limited years and regions. To fill this data gap, we produce a 500 m rainfed soy (Glycine max) sowing and harvest date dataset for Mato Grosso from 2004 to 2014 using a novel time series analysis method for Moderate Resolution Imaging Spectroradiometer (MODIS) satellite imagery, adapted for implementation in Google Earth Engine (GEE). Our estimates reveal that soy sowing and harvest dates varied widely (about 2 months) from field to field, confirming the need for spatially resolved crop timing information. An interannual trend toward earlier sowing dates occurred independently of variations in wet season onset, and may be attributed to an improvement in logistic or economic constraints that previously hampered early sowing. As anticipated, double cropped fields in which two crops are grown in succession are planted earlier than single cropped fields. This difference shrank, however, as sowing of single cropped fields occurred closer to the wet season onset in more recent years. The analysis offers insights about sowing behavior in response to historical climate variations which could be extended to understand sowing response under climate change in Mato Grosso., Soy cultivation; Sowing date; Mato Grosso; Climate change; Remote sensing; Time series analysis.

This study presents strategies to render triple-negative breast cancers sensitive to CDK4/6 inhibitors., Inhibitors of cyclin-dependent kinases CDK4 and CDK6 have been approved for treatment of hormone receptor–positive breast cancers. In contrast, triple-negative breast cancers (TNBCs) are resistant to CDK4/6 inhibition. Here, we demonstrate that a subset of TNBC critically requires CDK4/6 for proliferation, and yet, these TNBC are resistant to CDK4/6 inhibition due to sequestration of CDK4/6 inhibitors into tumor cell lysosomes. This sequestration is caused by enhanced lysosomal biogenesis and increased lysosomal numbers in TNBC cells. We developed new CDK4/6 inhibitor compounds that evade the lysosomal sequestration and are efficacious against resistant TNBC. We also show that coadministration of lysosomotropic or lysosome-destabilizing compounds (an antibiotic azithromycin, an antidepressant siramesine, an antimalaria compound chloroquine) renders resistant tumor cells sensitive to currently used CDK4/6 inhibitors. Lastly, coinhibition of CDK2 arrested proliferation of CDK4/6 inhibitor-resistant cells. These observations may extend the use of CDK4/6 inhibitors to TNBCs that are refractory to current anti-CDK4/6 therapies.

Hundreds of millions of the world's poorest people directly depend on smallholder farming systems. These people now face a changing climate and associated societal responses. We use mapping and a literature review to juxtapose the climate fate of smallholder systems with that of other agricultural systems and population groups. Limited direct evidence contrasts climate impact risk in smallholder agricultural systems versus other farming systems, but proxy evidence suggests high smallholder vulnerability. Smallholders distinctively adapt to climate shocks and stressors. Their future adaptive capacity is uncertain and conditional upon the severity of climate change and socioeconomic changes from regional development. Smallholders present a greenhouse gas (GHG) mitigation paradox. They emit a small amount of CO2 per capita and are poor, making GHG regulation unwarranted. But they produce GHG-intensive food and emit disproportionate quantities of black carbon through traditional biomass energy. Effectively accounting for smallholders in mitigation and adaption policies is critical and will require innovative solutions to the transaction costs that enrolling smallholders often imposes. Together, our findings show smallholder farming systems to be a critical fulcrum between climate change and sustainable development.

Despite a lack of supporting data, routine splenic flexure mobilization (SFM) during colectomy has been thought to reduce anastomotic leak (AL). We evaluated the impact of SFM on outcomes in distal colectomy.The 2005-2016 NSQIP database identified 66,068 patients undergoing distal colectomy with anastomosis. Cohorts were stratified by addition of SFM. Postoperative outcomes were compared between groups. Regression analysis identified factors affecting odds of developing AL.SFM was performed in 27,475 patients (41.6%). There was no difference in overall complications between cases with SFM and those without (p = 0.55). SFM had longer operative times (220 min vs. 184 min; p 0.0001). SFM was not associated with any difference in AL rate (3.6% vs. 3.7%; p = 0.86). Factors most associated with AL were lack of oral antibiotic preparation (OR 1.93; p 0.001), chemotherapy (OR 1.91; p 0.001), and weight loss (OR 1.68; p = 0.0005). Operative indication and approach did not affect leak.SFM in distal colectomy increased operative time without decreasing overall complications or AL. Routine splenic flexure mobilization may add risk without significant benefit.

Introduction Since inception of robotic-assisted surgery (RAS) in 1999, there has been an exponential rise in RAS in both number and complexity of surgical cases performed. The majority of these cases are gynecologic surgery in nature, with only a quarter of them labeled as general surgery. The purpose of this study is to determine if RAS in the Department of Defense (DoD) mirrors these trends. Methods A total of 6,204 RAS cases from across the DoD were reviewed between 01 January 2015 and 30 September 2017 from every Military Treatment Facility (MTF) that employs a robotic surgical device (various models of the da Vinci robotic surgical system by Intuitive Surgical). Specialty, number, and surgeon were recorded for each case. These end points were also examined for trends overtime and compared to similar civilian data. Results The number of MTFs performing robotic surgery and the number of cases performed increased significantly. An average of 373 cases per quarter-year were performed in 2015, 647 in 2016, and 708 in 2017. The number of RAS cases increased by about 10% every quarter-year during this time period. RAS was most commonly performed by general surgery in 10 of the 14 MTFs examined. Conclusions MTFs implemented RAS much later than the civilian world. However, since its implementation, the frequency of RAS use has increased at a faster rate in the DoD than in the civilian world. Possible reasons for this are a younger pool of surgeons in the military and less demands on cost-effective productivity, allowing these younger surgeons to focus on emerging technology rather than maximizing surgical cost efficiency. General surgery constitutes the majority of RAS cases in the DoD. It is unclear why this difference from the civilian world exists.

Background Modern 64- to 128-slice computed tomography (CT) scanners have questioned the need for routine colonoscopy after hospital admission for presumed uncomplicated diverticulitis. Methods This is a retrospective review of all patients (>18 years) who underwent planned colonoscopy after admission for Hinchey I or II acute diverticulitis (January 2009 to January 2014). The findings on the final radiologist report were then correlated with the colonoscopy results. Results In total, 110 patients (mean age, 55.2 ± 16; 46.4% female) underwent a subsequent colonoscopy (median, 60 days) after admission for diverticulitis. Overall, 102 patients (92.7%) had CT findings consistent with definitive diverticulitis, 6 patients had a diagnosis suggestive of diverticulitis on CT scan, and 2 patients had masses on their admission CT scans. Within the group with definitive diverticulitis, follow-up colonoscopy identified diverticulosis in 99 (97.0%), whereas the other 3 had normal findings. Of the patients with CT scans suggestive of diverticulitis, follow-up colonoscopy showed 3 with diverticulosis, 2 with malignancies, and 1 with nonspecific inflammation. The reliability of CT scans for diverticulitis compared with colonoscopy was found to have a kappa=.829 ( P Conclusions Follow-up colonoscopy should be performed when a CT scan suggests malignancy, nonspecific inflammatory findings, or the patient is otherwise due for routine screening or surveillance. In this study, there was no benefit of follow-up colonoscopy in patients with CT-confirmed diverticulitis in the absence of other concerning or indeterminate findings.

The rate and location of cropland expansion onto cattle pastures in Brazil could affect global food security, climate change, and economic growth. We combined mapping, statistical modeling, and qualitative methods to investigate patterns and processes of pasture to crop conversion (P2C) in Mato Grosso State (MT), Brazil, a globally important center of agricultural production. P2C land constituted 49% of cropland expansion from 2000 to 2013. For a random sample of 250 m pixels in MT, we estimated a regression model skilled at predicting P2C land in the rest of the state as a function of cattle ranching suitability, cropping suitability, and P2C conversion costs. Surprisingly, just 1/7 of pasture agronomically suitable for cultivation had undergone P2C. Hedonic regressions revealed that agronomic characteristics of land were associated with less than 20% of the variation in cropland suitability. Instead, the majority of the variation stemmed from a combination of proximity to agricultural infrastructure, characteristics of neighboring lands, and time fixed effects. The weak relationship between agronomic characteristics of land and P2C location suggests a less certain future for P2C than projections made with agronomic models. Consequentially, complications may arise for greenhouse gas mitigation policies in Brazil predicated on widespread expansion of cropland on pasture vs. natural areas. Our follow-up qualitative research shows that because P2C has often involved land rentals or sales, poorly functioning land institutions may have constrained P2C. Locally poor land quality, omitted from agronomic P2C predictions, can either catalyze or constrain P2C by limiting returns to ranching, farming, or both. Interventions to control rates and locations of P2C should take these insights into account.

Robotic surgery began approximately 30 years ago, growing steadily, and has now become one of the mainstream topics within the surgical literature across multiple surgical disciplines. More recently, robotic use has expanded to colorectal surgery, demonstrating increased usage in the more difficult operations involved. As competition in the marketplace and technology increase and improve, the size and cost of these systems may progressively decrease, and their presence will likely grow. With that, innovative and novel concepts are being introduced at a rapid pace. The enhanced performance gained by the surgeon with these devices will hopefully enable the difficult operations to become more feasible and potentially even safer. We present a brief history of the instruments related to robotic colorectal surgery and discuss some of the robotic instruments that may be seen in a future robotic-enabled operating room.

About 70% of agricultural output variance due to climate in Mato Grosso, Brazil was determined by changes in cropping frequency and/or changes in cropping area rather than yield (the most common climate impact indicator), a study now shows. The sensitivity of agricultural output to climate change has often been estimated by modelling crop yields under climate change scenarios or with statistical analysis of the impacts of year-to-year climatic variability on crop yields1,2. However, the area of cropland and the number of crops harvested per growing season (cropping frequency) both also affect agricultural output and both also show sensitivity to climate variability and change3,4,5,6,7,8,9. We model the change in agricultural output associated with the response of crop yield, crop frequency and crop area to year-to-year climate variability in Mato Grosso (MT), Brazil, a key agricultural region. Roughly 70% of the change in agricultural output caused by climate was determined by changes in frequency and/or changes in area. Hot and wet conditions were associated with the largest losses and cool and dry conditions with the largest gains. All frequency and area effects had the same sign as total effects, but this was not always the case for yield effects. A focus on yields alone may therefore bias assessments of the vulnerability of agriculture to climate change. Efforts to reduce climate impacts to agriculture should seek to limit production losses not only from crop yield, but also from changes in cropland area and cropping frequency.

BACKGROUND Intraoperative laser fluorescence angiography is a relatively new tool that can be used by colorectal surgeons to ensure adequate perfusion to bowel that remains after resection. It has been used mostly to determine an appropriate point of transection of the proximal bowel, as well as to ensure perfusion after the anastomosis has been constructed. We propose a different use of the technology in complex cases to ensure the ability to safely transect a major vascular pedicle and to ensure that perfusion will remain adequate. OBJECTIVE The purpose of this article is to describe a new use for fluorescence angiography technology. DESIGN This is a technical note. SETTINGS The work was conducted at a tertiary care military medical center. PATIENTS Patients included individuals requiring oncologic colorectal resection where the status of 1 major vascular pedicle was unknown or impaired. MAIN OUTCOME MEASURES We assessed perfusion after occlusion of a major vascular pedicle for the short term in hospital outcomes. RESULTS Adequate studies were obtained, and perfusion was maintained in both patients. Oncologic resections were performed, and short-term outcomes were comparable with any individual undergoing these procedures. LIMITATIONS This study was limited because it is early experience that was not performed in the setting of a scientific investigation. CONCLUSIONS Application of intraoperative fluorescence angiography in this setting appears to be safe and may assist the surgeon in estimating reliable vascular perfusion in patients such as these who require oncologic colorectal resection.

1065 Background: The acquisition of ligand-independent ESR1 mutations during endocrine therapy in metastatic ER+ breast cancer is a common mechanism of resistance to endocrine treatment, particularly aromatase inhibitors, and found in more than 30% of patients with metastatic ER+ breast cancer. Our recent work showed that the ER mutations confer resistance to currently available endocrine treatments while promoting an aberrant ER transcriptional activity that drives metastases. These results underscore the importance of targeting the ESR1 mutations even after the development of endocrine resistance. We hypothesized that during chemotherapy treatment, the ESR1 mutations remain an important driver of tumor growth and metastases and therefore drugs targeting the ESR1 mutation could enhance the efficacy of chemotherapy. In this study we investigated the combination of chemotherapy with the selective estrogen receptor degrader in the presence of WT and mutant ER. Methods: We performed synergy studies testing the combination of fulvestrant with chemotherapy treatments commonly used in ER+ metastatic breast cancer including 5FU (representing capecitabine), adriamycin and paclitaxel using MCF7 and T47D breast cancer cell lines engineered to express doxycycline inducible Y537S-ESR1 mutation. Results: We found that in MCF7 cells the combination of chemotherapy and fulvestrant was synergistic and the synergy was augmented with the induction of the Y537S mutation. In contrast, there was no synergy in T47D cells that harbor a P53 mutation. We confirmed that the synergistic activity of fulvestrant with chemotherapy is dependent on P53 by generating P53 knock-out MCF7 cells using CRISPR-cas9. Additionally, cell cycle and apoptosis analyses showed that the synergistic activity was mainly due to increased effects on G1 arrest rather than apoptosis. Conclusions: Our study indicates that chemotherapy and fulvestrant are synergistic in ER+ breast cancer and the synergy is increased in the presence of the Y537S ESR1 mutation and is dependent on P53 activity. These results support a clinical trial testing the addition of fulvestrant or other novel selective estrogen receptor degraders in patients with metastatic ER+ breast cancer who are starting chemotherapy treatment.

In the United States, few constituents know and understand climate policy, prioritize it as a political topic, or let their voting decisions depend on it. In these conditions, representatives would not be expected to pay heed to constituents’ climate concern in their voting decisions. Still, even after controlling for the presence of interest groups, campaign finance, and legislators’ party affiliation and ideology, there is a consistent link between public opinion and votes on cap-and-trade legislation in the House (and to a lesser degree in the Senate). The same is true when public opinion is simulated based on pre-vote district characteristics. Explanations for these findings are discussed.

We reviewed studies addressing the extent to which more integrated agricultural systems (IAS) have been found to be more resilient to climate variability and climate change than more specialized agricultural systems. We found limited literature directly addressing the topic, necessitating the use of proxy measures to enlarge the sample. Where necessary, we used agricultural system richness and diversity as proxies for the presence of the sort of synergistic relationships that typify IAS, interannual climate variability for climate change, and myriad agricultural indicators for resilience. We found that (1) 37 papers addressed the topic either through mathematical modeling or statistical modeling; (2) in the statistical papers, integration was overwhelmingly (n = 17/24) associated with increased climate resilience; (3) these findings stemmed mainly from comparisons of more versus less diverse or rich farming systems, while few studies investigated the influence of farm system synergies on resilience; (4) yield, revenue, profit, and yield variance were all used to demonstrate resilience; (5) modeling studies tended to investigate resilience across multiple years, while most statistical approaches tracked single-year outcomes; (6) the IAS-climate resilience links demonstrated were not generalizable across units of analysis, spatiotemporal scale, and from autonomous to directed integration; and (7) few of the articles reviewed identified and measured the mechanism by which IAS were shown to have conferred resilience. Our findings reveal suggestive, although by no means conclusive, evidence that farm system integration can enhance resilience and highlight the need for research to test whether integration policies can have similar outcomes. WIREs Clim Change 2017, 8:e461. doi: 10.1002/wcc.461 For further resources related to this article, please visit the WIREs website.

Aims: To determine whether day and time of admission influences the practice patterns of the admitting general surgeon and subsequent outcomes for patients diagnosed with small bowel obstruction. Methods: A retrospective database review was carried out, covering patients admitted with the presumed diagnosis of partial small bowel obstruction from 2004–2011. Results: A total of 404 patients met the inclusion criteria. One hundred and thirty-nine were admitted during the day, 93 at night and 172 on the weekend. Overall 30.2% of the patients were managed operatively with no significant difference between the groups (P = 0.89); however, of patients taken to the operating room, patients admitted during the day received operative intervention over 24 hours earlier than those admitted at a weekend, 0.79 days vs 1.90 days, respectively (P = 0.05). Overall mortality was low at 1.7%, with no difference noted between the groups (P = 0.35). Likewise there was no difference in morbidity rates between the three groups (P = 0.90). Conclusions: Despite a faster time to operative intervention in those patients admitted during the day, our study revealed that time of admission does not appear to correlate to patient outcome or mortality.

Background Discrepancies in socioeconomic factors have been associated with higher rates of perforated appendicitis. As an equal-access health care system theoretically removes these barriers, we aimed to determine if remaining differences in demographics, education, and pay result in disparate outcomes in the rate of perforated appendicitis. Materials and methods All patients undergoing appendectomy for acute appendicitis (November 2004–October 2009) at a tertiary care equal access institution were categorized by demographics and perioperative data. Rank of the sponsor was used as a surrogate for economic status. A multivariate logistic regression model was performed to determine patient and clinical characteristics associated with perforated appendicitis. Results A total of 680 patients (mean age 30 ± 16 y; 37% female) were included. The majority were Caucasian (56.4% [n = 384]; African Americans 5.6% [n = 38]; Asians 1.9% [n = 13]; and other 48.9% [n = 245]) and enlisted (87.2%). Overall, 6.4% presented with perforation, with rates of 6.6%, 5.8%, and 6.7% (P = 0.96) for officers, enlisted soldiers, and contractors, respectively. There was no difference in perforation when stratified by junior or senior status for either officers or enlisted (9.3% junior versus 4.40% senior officers, P = 0.273; 6.60% junior versus 5.50% senior enlisted, P = 0.369). On multivariate analysis, parameters such as leukocytosis and temperature, as well as race and rank were not associated with perforation (P = 0.7). Only age had a correlation, with individuals aged 66–75 y having higher perforation rates (odds ratio, 1.04; 95% confidence interval, 1.02–1.05; P Conclusions In an equal-access health care system, older age, not socioeconomic factors, correlated with increased appendiceal perforation rates.

Introduction Internal hernias (IHs) occur more frequently in laparoscopic gastric bypass (LGB) surgery than in the classic open procedure. The incidence of small bowel obstruction after LGB ranges from 1.8% and 9.7%. Some have theorized that this occurs because of decreased adhesion formation. Methods The mesenteric irritation technique is performed after closure of the jejunojejunal mesenteric defect with a running 2-0 silk suture. A sponge is then rubbed against the closed visceral peritoneal mesentery until petechiae are visualized on the surface of the mesentery. Results In all, 338 LGBs were performed using the standard closure technique with an IH incidence of 5.3% (range 1.7% to 7.8%). When using the mesenteric irritation technique, 72 LGBs were performed with an IH rate of 1.4% (P = .13). Conclusions Mesenteric irritation is a novel technique performed with minimal additional time and no additional equipment. This technique may prove beneficial in reducing the incidence of IHs.

This study examines whether policies to encourage cattle ranching intensification in Brazil can abate global greenhouse gas (GHG) emissions by sparing land from deforestation. We use an economic model of global land use to investigate, from 2010 to 2030, the global agricultural outcomes, land use changes, and GHG abatement resulting from two potential Brazilian policies: a tax on cattle from conventional pasture and a subsidy for cattle from semi-intensive pasture. We find that under either policy, Brazil could achieve considerable sparing of forests and abatement of GHGs, in line with its national policy targets. The land spared, particularly under the tax, is far less than proportional to the productivity increased. However, the tax, despite prompting less adoption of semi-intensive ranching, delivers slightly more forest sparing and GHG abatement than the subsidy. This difference is explained by increased deforestation associated with increased beef consumption under the subsidy and reduced deforestation associated with reduced beef consumption under the tax. Complementary policies to directly limit deforestation could help limit these effects. GHG abatement from either the tax or subsidy appears inexpensive but, over time, the tax would become cheaper than the subsidy. A revenue-neutral combination of the policies could be an element of a sustainable development strategy for Brazil and other emerging economies seeking to balance agricultural development and forest protection.

Aim Urgent colectomy for severe Clostridium difficile infection can be associated with increased morbidity and mortality. We aimed to use endoscopic methods for treatment. Method We describe a technique of placing an intracolonic tube facilitating decompression and direct delivery of vancomycin to the proximal colon along with enemas on a regular and frequent basis that may not be possible with vancomycin enemas alone. Results Successful resolution of the C. difficile infection and avoidance of surgery. Conclusion While further long-term evaluation is required, our initial results have shown it to be effective in treating select patients with recalcitrant Clostridium difficile-associated megacolon.

Surgical resection remains a mainstay of treatment and is highly effective for localized colorectal cancer. However, ~30-40% of patients develop recurrence following surgery and 40-50% of recurrences are apparent within the first few years after initial surgical resection. Several variables factor into the ultimate outcome of these patients, including the extent of disease, tumor biology, and patient co-morbidities. Additionally, the time from initial treatment to the development of recurrence is strongly associated with overall survival, particularly in patients who recur within one year of their surgical resection. Current post-resection surveillance strategies involve physical examination, laboratory, endoscopic and imaging studies utilizing various high and low-intensity protocols. Ultimately, the goal is to detect recurrence as early as possible, and ideally in the asymptomatic localized phase, to allow initiation of treatment that may still result in cure. While current strategies have been effective, several efforts are evolving to improve our ability to identify recurrent disease at its earliest phase. Our aim with this article is to briefly review the options available and, more importantly, examine emerging and future options to assist in the early detection of colon and rectal cancer recurrence.

Treatment of advanced colon and rectal cancer has significantly evolved with the introduction of neoadjuvant chemoradiation therapy so much that, along with more effective chemotherapy regimens, surgery has been considered unnecessary among some institutions for select patients. The tumor response to these treatments has also improved and ultimately has been shown to have a direct effect on prognosis. Yet, the best way to monitor that response, whether clinically, radiologically, or with laboratory findings, remains controversial. The authors' aim is to briefly review the options available and, more importantly, examine emerging and future options to assist in monitoring treatment response in cases of locally advanced rectal cancer and metastatic colon cancer.

The expansion of crop agriculture onto low productivity cattle pastures in the agricultural frontier of Brazil is a form of agricultural intensification that can help to contribute to global food and climate goals. However, the amount of pasture to crop conversion in the region lags both agronomic and economic potential. We administered a survey in combination with a lab-in-the-field experiment to 559 farmers in Mato Grosso, Brazil. We used the results to explore behavioral determinants of pasture to crop conversion. We compared farmers choices across two rounds of a risk game meant to mimic the economic risk of decisions to convert pasture to crops. We found framing the risk game to concern agriculture profoundly altered subjects’ experimental choices. These discrepancies involved the majority of experimental subjects, and were highly heterogenous in nature. They were also somewhat predictive of subjects’ behavior converting pasture to cropland. Our findings indicate that farmers may make economic decisions involving agriculture and/or agricultural land differently from other economic decisions. Our finding is of relevance for research into the propensity of farmers to intensify and for policies seeking to influence rates of agricultural intensification.

This review analyzes the methods being used and developed in global environmental governance (GEG), an applied field that employs insights and tools from a variety of disciplines both to understand pressing environmental problems and to determine how to address them collectively. We find that methods are often underspecified in GEG research. We undertake a critical review of data collection and analysis in three categories: qualitative, quantitative, and modeling and scenario building. We include examples and references from recent studies to show when and how best to utilize these different methods to conduct problem-driven research. GEG problems are often characterized by institutional and issue complexity, linkages, and multiscalarity that pose challenges for many conventional methodological approaches. As a result, given the large methodological toolbox available to applied researchers, we recommend they adopt a reflective, pluralist, and often collaborative approach when choosing methods appropriate to these challenges.

Outpatient surgery is performed widely throughout the Army Medical Command (MEDCOM). It is common practice throughout Medical Command to admit barracks dwelling active duty service members (ADSMs) undergoing ambulatory surgical procedures for overnight observation. We hypothesized that overnight observation of these individuals has not prevented adverse outcomes that would have otherwise occurred if the patient had been discharged to the barracks.We reviewed the postoperative course of all ADSMs undergoing ambulatory surgery with subsequent overnight hospital stay because of primary barracks residence. Procedures included hernia repair, lipoma excisions, and pilonidal cystectomies. Inclusion criteria were ADSMs who stayed overnight purely on the basis of their military barracks residence.145 patients met our inclusion criteria. Their mean age was 23 ± 3.2, 90.9% were males. The mean hospital length of stay was 24 ± 11.4 hours. There were four (2.78%) postoperative complications, three patients with postoperative urinary retention, and one patient with mild bleeding from a pilonidal excision site, all within 8 hours postoperatively. No adverse outcomes were noted during the period of their hospitalization.Barracks dwelling ADSMs do not have adverse outcomes during their inpatient observational hospitalization. An outpatient escort would be sufficient to ensure adequate observation.

Our recent article, “Are Brazil's Deforesters Avoiding Detection?” demonstrated that focusing illegal deforestation enforcement on the subset of forest monitored by the flagship PRODES system has caused PRODES to capture a declining share of deforestation in the Brazilian Amazon. Deforesters may be purposively seeking out forests not monitored for enforcement. Addressing the problem would help Brazil maintain a cutting‐edge forest governance model worthy of transfer to other nations. Two commentaries questioned our decision to investigate solely PRODES and not additional government monitoring systems. We focused on PRODES because it is the most salient deforestation monitoring system. Other key deforestation monitoring systems are all either limited to the same monitoring footprint as PRODES, not used for enforcement, or are rarely used for measuring forest loss in the Brazilian Amazon. We do agree with the commentaries that Brazil's new satellite monitoring protocol for greenhouse gas emissions estimation is critical progress of the type we were advocating in our original article.

Along agricultural frontiers, non-governmental organizations are developing agricultural certification systems for use as conservation tools. In this article, we propose a typology of certification systems that we use to frame a critical examination of the efficacy of these systems and their limitations in achieving conservation goals. On the basis of these findings, we recommend improved management practices. Our analysis draws on case studies that examine the use of certification to regulate two very distinct production systems: smallholder shade coffee cooperatives in El Salvador and industrial scale soy and beef operations in the Brazilian Amazon. Despite their disparate contexts, both case studies demonstrate that agricultural certification to achieve conservation goals is difficult to design, implement, and evaluate. Certifiers must enroll consumers and firms who do not prioritize conservation goals, navigate scientific uncertainty regarding best conservation practices, and also market their brand a...

Listeria monocytogenes is a pathogen associated with meningitis in the immunosuppressed patient. The pathogen is usually found in soft cheeses and raw milk. We present a case of an infected popliteal artery stent graft with Listeria monocytogenes. The report focuses on the diagnosis and treatment with surgical explantation and vascular reconstruction.

Anal fistula (AF) presents a chronic problem for patients and colorectal surgeons alike. Surgical treatment may result in impairment of continence and long-term risk of recurrence. Treatment options for AFs vary according to their location and complexity. The ideal approach should result in low recurrence rates and minimal impact on continence. New technical approaches involving biologically derived products such as biological mesh, fibrin glue, fistula plug, and stem cells have been applied in the treatment of AF to improve outcomes and decrease recurrence rates and the risk of fecal incontinence. In this review, we will highlight the current evidence and describe our personal experience with these novel approaches.

The tropics are a critical nexus of important environmental services and resources, productive lands that are critical to feeding the planet in years to come, and rural economies beset by disease and malnutrition, and in need of economic development. This special issue synthesizes a series of multidisciplinary dialogues aiming to examine the complex challenge of tropical agricultural systems. The work contained five principle themes: (a) The future of tropical agriculture is vital for developing world economies and the global environment in ways that scholars are still working to characterize. (b) The tropics are highly socioeconomically and environmentally heterogeneous. (c) We expect sociocultural and institutional factors to strongly shape the future of tropical agriculture and the environment. (d) Sustainable tropical agriculture means linking smallholders, the vast bulk of farmers, with commercial agriculture, the vast bulk of agribusiness. (d) Scholarship from the environmental sciences can help to ...

One in every five patches of tropical forest near agriculture in Brazil appears to contribute more to agricultural production by preventing crop-killing extreme heat exposure than it could produce ...

Approved drugs target approximately 400 different mechanisms of action, of which as few as 60 are currently used as anti-cancer therapies. Given that on average it takes 10–15 years for a new cancer therapeutic to be approved, and the recent success of drug repurposing for agents such as thalidomide, we hypothesized that effective, safe cancer treatments may be found by testing approved drugs in new therapeutic settings. Here, we report in-vivo testing of a broad compound collection in cancer xenograft models. Using 182 compounds that target 125 unique target mechanisms, we identified 3 drugs that displayed reproducible activity in combination with the chemotherapeutic temozolomide. Candidate drugs appear effective at dose equivalents that exceed current prescription levels, suggesting that additional pre-clinical efforts will be needed before these drugs can be tested for efficacy in clinical trials. In total, we suggest drug repurposing is a relatively resource-intensive method that can identify approved medicines with a narrow margin of anti-cancer activity.

Reliable experimental evidence provides a firm scientific foundation for only a minority of the clinical decisions primary care practitioners must make each day. Thus clinicians' experience and judgment must complement and supplement their knowledge of published research studies. This presents a dynamic and difficult challenge to the practitioner—one that is magnified when combined with the never ending influx of medical information, with patients' and physicians' uneasiness with clinical uncertainty, and with new external pressures to standardize care. With these factors in mind, this article will review evidence-based medicine, a process and philosophy for the practice and teaching of clinical medicine that has sparked much controversy in recent years. Clinical scenarios commonly encountered in adult primary care—cute low back pain, hypertension, and screening for vascular disease—illustrate some strengths and limitations of evidence-based medicine.

Cefazolin, a first generation cephalosporin, is a rare cause of cyclical fevers, neutropenia, and thrombocytopenia following surgical prophylaxis. We present the case of an otherwise healthy 21-year-old male who sustained a 50-cm laceration to his chest and abdomen. He received emergency department prophylaxis with cefazolin and surgical repair. Subsequently, he developed cyclical fevers, neutropenia, and thrombocytopenia, all of which resolved after antibiotic discontinuation. This is the first case report in which the perioperative administration of cefazolin following trauma resulted in significant neutropenia and thrombocytopenia. Also discussed in this report are the etiology, workup, and treatment of cefazolin-induced neutropenia.

Biomass can help reduce greenhouse gas (GHG) emissions by displacing petroleum in the transportation sector, by displacing fossil-based electricity, and by sequestering atmospheric carbon. Which use mitigates the most emissions depends on market and regulatory contexts outside the scope of attributional life cycle assessments. We show that bioelectricity's advantage over liquid biofuels depends on the GHG intensity of the electricity displaced. Bioelectricity that displaces coal-fired electricity could reduce GHG emissions, but bioelectricity that displaces wind electricity could increase GHG emissions. The electricity displaced depends upon existing infrastructure and policies affecting the electric grid. These findings demonstrate how model assumptions about whether the vehicle fleet and bioenergy use are fixed or free parameters constrain the policy questions an analysis can inform. Our bioenergy life cycle assessment can inform questions about a bioenergy mandate's optimal allocation between liquid fuels and electricity generation, but questions about the optimal level of bioenergy use require analyses with different assumptions about fixed and free parameters.

Objective To report the relationship between disease activity and health-related quality of life (HRQoL) in relapsing multiple sclerosis, and the impact of natalizumab. Methods HRQoL data were available from 2,113 multiple sclerosis patients in natalizumab clinical studies. In the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis (AFFIRM) study, patients received natalizumab 300mg (n = 627) or placebo (n = 315); in the Safety and Efficacy of Natalizumab in Combination with Interferon Beta-1a in Patients with Relapsing Remitting Multiple Sclerosis (SENTINEL) study, patients received interferon beta-1a (IFN-β-1a) plus natalizumab 300mg (n = 589), or IFN-β-1a plus placebo (n = 582). The Short Form-36 (SF-36) and a subject global assessment visual analog scale were administered at baseline and weeks 24, 52, and 104. Prespecified analyses included changes from baseline to week 104 in SF-36 and visual analog scale scores. Odds ratios for clinically meaningful improvement or worsening on the SF-36 Physical Component Summary (PCS) and Mental Component Summary were calculated. Results Mean baseline SF-36 scores were significantly less than the general US population and correlated with Expanded Disability Status Scale scores, sustained disability progression, relapse number, and increased volume of brain magnetic resonance imaging lesions. Natalizumab significantly improved SF-36 PCS and Mental Component Summary scores at week 104 in AFFIRM. PCS changes were significantly improved by week 24 and at all subsequent time points. Natalizumab-treated patients in both studies were more likely to experience clinically important improvement and less likely to experience clinically important deterioration on the SF-36 PCS. The visual analog scale also showed significantly improved HRQoL with natalizumab. Interpretation HRQoL was impaired in relapsing multiple sclerosis patients, correlated with severity of disease as measured by neurological ratings or magnetic resonance imaging, and improved significantly with natalizumab. Ann Neurol 2007

OBJECTIVE: To determine if structured teaching of bedside cardiac examination skills improves medical residents’ examination technique and their identification of key clinical findings. DESIGN: Firm-based single-blinded controlled trial. SETTING: Inpatient service at a university-affiliated public teaching hospital. PARTICIPANTS: Eighty Internal Medicine residents. METHODS: The study assessed 2 intervention groups that received 3-hour bedside teaching sessions during their 4-week rotation using either: (1) a traditional teaching method, “demonstration and practice” (DP) (n=26) or (2) an innovative method, “collaborative discovery” (CD) (n=24). The control group received their usual ward teaching sessions (n=25). The main outcome measures were scores on examination technique and correct identification of key clinical findings on an objective structured clinical examination (OSCE). RESULTS: All 3 groups had similar scores for both their examination technique and identification of key findings in the preintervention OSCE. After teaching, both intervention groups significantly improved their technical examination skills compared with the control group. The increase was 10% (95% confidence interval [CI] 4% to 17%) for CD versus control and 12% (95% CI 6% to 19%) for DP versus control (both P

This letter uses satellite remote sensing to examine patterns of cropland expansion, cropland abandonment, and changing cropping frequency in Mato Grosso, Brazil from 2001 to 2011. During this period, Mato Grosso emerged as a globally important center of agricultural production. In 2001, 3.3 million hectares of mechanized agriculture were cultivated in Mato Grosso, of which 500 000 hectares had two commercial crops per growing season (double cropping). By 2011, Mato Grosso had 5.8 million hectares of mechanized agriculture, of which 2.9 million hectares were double cropped. We found these agricultural changes to be selective with respect to land attributes?significant differences (p?0.001) existed between the land attributes of agriculture versus non-agriculture, single cropping versus double cropping, and expansion versus abandonment. Many of the land attributes (elevation, slope, maximum temperature, minimum temperature, initial soy transport costs, and soil) that were associated with an increased likelihood of expansion were associated with a decreased likelihood of abandonment (p?

To determine the relationship between brain energy metabolites and neurologic status after ischemia-hypoxia, we measured cortical tissue levels of adenosine triphosphate (ATP), phosphocreatine, and lactate. Rats with permanent unilateral carotid occlusion were exposed to 5, 10, and 15 min of hypoxic atmosphere (FIO2 0.048) and, to examine metabolic restitution, 60 min after recovery in rats exposed to the same hypoxic mixture for 15 min. At 5 and 10 min of hypoxia, there were significant reductions in phosphocreatinine and elevations in tissue lactate, but only after 15 min of hypoxia, did ATP levels significantly decrease. By 60 min after recovery, phosphocreatinine values returned to the normal range, ATP values to 15% less than normal, and tissue lactate toward normal. In parallel survival studies, neurological status was examined following hypoxic exposure (PaO2 18 to 19 torr) for 5 an 10 min. Evidence for neurological injury in the form of posthypoxic seizures occurred at a point in time preceding significant changes in brain tissue ATP level. Since injury occurs prior to ATP reduction, changes in brain tissue ATP level may not be an appropirate endpoint for determining brain tissue injury in hypoxia.

Recovery from herpes simplex of the mouth occurred within 24 to 48 hours when cryotherapy was applied with in three days of the appearance of vesicles. In all but two of the 127 patients treated, a single treatment was sufficient to stop the morbid process. When treatment was applied at the onset of prodromic symptoms, vesicular formation ceased.