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Abstract Background In addition to radiological evaluation, biomarkers may be useful in providing early information on the response to treatment, and supporting clinical decision‐making. The objective of this study was to investigate carcinoembryonic antigen (CEA) and lactate dehydrogenase (LDH) as biomarkers for early assessment of response in patients with advanced non‐small cell lung cancer (NSCLC) treated with platinum‐based chemotherapy. Methods A retrospective follow‐up study was conducted from 2012 to 2017 among 593 consecutive patients with advanced NSCLC treated with first‐line platinum‐based chemotherapy in a large teaching hospital in the Netherlands. Pretreatment biomarker levels and changes from pretreatment levels were studied for association with radiologic response (partial response [PR] or complete response [CR], according to RECIST 1.1) using multivariate logistic regression, and with overall survival using COX proportional hazard modeling. Patient and disease characteristics such as age and disease stage were taken into account as potential confounding factors. Results Decreases in CEA and LDH (≥ 20%), particularly early in treatment, were significantly associated with better radiological response. Increases in these biomarkers (≥ 20%) and high pretreatment LDH levels (≥ 247 U/L) were significantly associated with lower overall survival. Conclusions Our results support determination of CEA and LDH levels for earlier assessment of response to platinum‐based chemotherapy in patients with advanced NSCLC. Hence, routine determination and evaluation of CEA and LDH levels, prior to each cycle of platinum‐based chemotherapy in advanced NSCLC, should be considered as part of daily clinical practice. Key points Significant findings of the study Serum biomarkers in monitoring of treatment in advanced NSCLC would be useful. CEA and LDH decrease (≥ 20%) is favorable for achieving radiological response. High LDH levels and CEA/LDH increase (≥ 20%) is associated with reduced survival. What this study adds Monitoring of CEA seems to be particularly relevant in early stage of treatment. CEA and LDH determination should be considered as part of daily clinical practice.

Abstract Background Women and children suffer disproportionately in armed-conflicts. Since 2011, the protracted Syrian crisis has fragmented the pre-existing healthcare system. Despite the massive health needs of women and children, the delivery of key reproductive, maternal, newborn, child and adolescent health and nutrition (RMNCAH&N) interventions, and its underlying factors are not well-understood in Syria. Our objective was to document intervention coverage indicators and their implementation challenges inside Syria during conflict. Methods We conducted 1) a desk review to extract RMNCAH&N intervention coverage indicators inside Syria during the conflict; and 2) qualitative interviews with decision makers and health program implementers to explore reasons behind provision/non-provision of RMNCAH&N interventions, and the rationale informing decisions, priorities, collaborations and implementation. We attempt to validate findings by triangulating data from both sources. Results Key findings showed that humanitarian organisations operating in Syria adopted a complex multi-hub structure, and some resorted to remote management to improve accessibility to certain geographic areas. The emergency response prioritised trauma care and infectious disease control. Yet, with time, humanitarian organisations successfully advocated for prioritising maternal and child health and nutrition interventions given evident needs. The volatile security context had implications on populations’ healthcare seeking behaviors, such as women reportedly preferring home births, or requesting Caesarean-sections to reduce insecurity risks. Additional findings were glaring data gaps and geographic variations in the availability of data on RMNCAH&N indicators. Adaptations of the humanitarian response included task-shifting to overcome shortage in skilled healthcare workers following their exodus, outreach activities to enhance access to RMNCAH&N services, and operating in ‘underground’ facilities to avoid risk of attacks. Conclusion The case of Syria provides a unique perspective on creative ways of managing the humanitarian response and delivering RMNCAH&N interventions, mainly in the multi-hub structure and use of remote management, despite encountered challenges. The scarcity of RMNCAH&N data is a tremendous challenge for both researchers and implementing agencies, as it limits accountability and monitoring, thus hindering the evaluation of delivered interventions.

Background Selected patients with colorectal peritoneal metastases are treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The concentration of intraperitoneal chemotherapy reflects the administered dose and perfusate volume. The aim of this study was to calculate intraperitoneal chemotherapy concentration during HIPEC and see whether this was related to clinical outcomes. Methods An observational multicentre study included consecutive patients with colorectal peritoneal metastases who were treated with CRS–HIPEC between 2010 and 2018 at three Dutch centres. Data were retrieved from prospectively developed databases. Chemotherapy dose and total circulating volumes of carrier solution were used to calculate chemotherapy concentrations. Postoperative complications, disease‐free and overall survival were correlated with intraoperative chemotherapy concentrations. Univariable and multivariable logistic regression, Cox regression and survival analyses were performed. Results Of 320 patients, 220 received intraperitoneal mitomycin C (MMC) and 100 received oxaliplatin. Median perfusate volume for HIPEC was 5·0 (range 0·7–10·0) litres. Median intraperitoneal chemotherapy concentration was 13·3 (range 7·0–76·0) mg/l for MMC and 156·0 (91·9–377·6) mg/l in patients treated with oxaliplatin. Grade III or higher complications occurred in 75 patients (23·4 per cent). Median overall survival was 36·9 (i.q.r. 19·5–62·9) months. Intraperitoneal chemotherapy concentrations were not associated with postoperative complications or survival. Conclusion CRS–HIPEC was performed with a wide variation in intraperitoneal chemotherapy concentrations that were not associated with complications or survival.

Abstract Background Low skeletal muscle index (SMI) in metastatic colorectal cancer (mCRC) patients is associated with poor outcomes. The prognostic impact of SMI changes during consecutive palliative systemic treatments is unknown. Methods This is a retrospective analysis of the phase 3 CAIRO3 study. The CAIRO3 study randomized 557 patients between maintenance capecitabine + bevacizumab (CAP‐B) or observation, after six cycles capecitabine + oxaliplatin + bevacizumab (CAPOX‐B). Upon first disease progression (PD1), CAPOX‐B was reintroduced until second progression (PD2). SMI was assessed by computed tomography (CT) (total 1355 scans). SMI and body mass index (BMI) changes were analyzed for three time‐periods; p1: during initial CAPOX‐B, p2: randomization to PD1, and p3: PD1 to PD2. The association between absolute and change in SMI and BMI (both per 1 standard deviation) during p1‐p3, with PD1, PD2, and survival was studied by Cox regression models. Results This analysis included 450 of the 557 patients randomized in the CAIRO3 study. Mean SMI decreased during p1: mean −0.6 SMI units [95% CI −1.07;‐0.26] and p3: −2.2 units [−2.7;‐1.8], whereas during p2, SMI increased + 1.2 units [0.8‐1.6]. BMI changes did not reflect changes in SMI. SMI loss during p2 and p3 was significantly associated with shorter survival (HR 1.19 [1.09‐1.35]; 1.54 [1.31‐1.79], respectively). Sarcopenia at PD1 was significantly associated with early PD2 (HR 1.40 [1.10‐1.70]). BMI loss independent of SMI loss was only associated with shorter overall survival during p3 (HR 1.35 [1.14‐1.63]). Conclusions In mCRC patients, SMI loss during palliative systemic treatment was related with early disease progression and reduced survival. BMI did not reflect changes in SMI and could not identify patients at risk of poor outcome during early treatment lines.

Abstract It is expected that Brazil could play an important role in biojet fuel (BJF) production in the future due to the long experience in biofuel production and the good agro‐ecological conditions. However, it is difficult to quantify the techno‐economic potential of BJF because of the high spatiotemporal variability of available land, biomass yield, and infrastructure as well as the technological developments in BJF production pathways. The objective of this research is to assess the recent and future techno‐economic potential of BJF production in Brazil and to identify location‐specific optimal combinations of biomass crops and technological conversion pathways. In total, 13 production routes (supply chains) are assessed through the combination of various biomass crops and BJF technologies. We consider temporal land use data to identify potential land availability for biomass production. With the spatial distribution of the land availability and potential yield of biomass crops, biomass production potential and costs are calculated. The BJF production cost is calculated by taking into account the development in the technological pathways and in plant scales. We estimate the techno‐economic potential by determining the minimum BJF total costs and comparing this with the range of fossil jet fuel prices. The techno‐economic potential of BJF production ranges from 0 to 6.4 EJ in 2015 and between 1.2 and 7.8 EJ in 2030, depending on the reference fossil jet fuel price, which varies from 19 to 65 US$/GJ across the airports. The techno‐economic potential consists of a diverse set of production routes. The Northeast and Southeast region of Brazil present the highest potentials with several viable production routes, whereas the remaining regions only have a few promising production routes. The maximum techno‐economic potential of BJF in Brazil could meet almost half of the projected global jet fuel demand toward 2030.

Background: This study used novel human neurophysiologic models to investigate whether the mechanism of rate-sensitive H-reflex depression lies in the pre-synaptic or post-synaptic locus in humans. We hypothesized that pre-synaptic inhibition would suppress Ia afferents and H-reflexes without suppressing alpha motor neurons or motor evoked potentials (MEPs). In contrast, post-synaptic inhibition would suppress alpha motor neurons, thereby reducing H-reflexes and MEPs. Methods: We recruited 23 healthy adults with typical rate-sensitive H-reflex depression, 2 participants with acute sensory-impaired spinal cord injury (SCI) (to rule out influence of sensory stimulation on supra-spinal excitability), and an atypical cohort of 5 healthy adults without rate-sensitive depression. After a single electrical stimulation to the tibial nerve, we administered either a testing H-reflex or a testing MEP at 50–5000 ms intervals. Results: Testing MEPs were not diminished in healthy subjects with or without typical rate-sensitive H-reflex depression, or in subjects with sensory-impaired SCI. MEP responses were similar in healthy subjects with versus without rate-sensitive H-reflex depression. Conclusions: Results from these novel in vivo human models support a pre-synaptic locus of rate-sensitive H-reflex depression for the first time in humans. Spinal reflex excitability can be modulated separately from descending corticospinal influence. Each represents a potential target for neuromodulatory intervention. Keywords: H-reflex, Motor evoked potential, Pre-synaptic, Soleus, Spinal cord, Spinal cord injury

Over two decades ago acellular pertussis vaccines (aP) replaced whole cell pertussis vaccines (wP) in several countries. Since then, a resurgence in pertussis has been observed, which is hypothesized to be linked, in part, to waning immunity. To better understand why waning immunity occurs, we developed a long-term outbred CD1 mouse model to conduct the longest murine pertussis vaccine studies to date, spanning out to 532 days post primary immunization. Vaccine-induced memory results from follicular responses and germinal center formation; therefore, cell populations and cytokines involved with memory were measured alongside protection from challenge. Both aP and wP immunization elicit protection from intranasal challenge by decreasing bacterial burden in both the upper and lower airways, and by generation of pertussis specific antibody responses in mice. Responses to wP vaccination were characterized by a significant increase in T follicular helper cells in the draining lymph nodes and CXCL13 levels in sera compared to aP mice. In addition, a population of B. pertussis+ memory B cells was found to be unique to wP vaccinated mice. This population peaked post-boost, and was measurable out to day 365 post-vaccination. Anti-B. pertussis and anti-pertussis toxoid antibody secreting cells increased one day after boost and remained high at day 532. The data suggest that follicular responses, and in particular CXCL13 levels in sera, could be monitored in pre-clinical and clinical studies for the development of the next-generation pertussis vaccines.

Abstract Background Cyclin‐dependent kinase (CDK) 4/6 inhibitors have recently been approved for the treatment of hormone receptor–positive and HER2‐negative metastatic breast cancer in association with endocrine therapy in postmenopausal women. Data on the interaction of CDK4/6 inhibition and radiotherapy are scarce, but some studies show unexpected toxicity. Cases We report three cases of unexpected severe or prolonged soft tissue, skin, and gastrointestinal toxicity in patients treated with a combination of radiotherapy and the CDK4/6 inhibitor palbociclib. Conclusion These cases indicate a possible interaction between radiotherapy and palbociclib. Therefore, we recommend using radiotherapy cautiously when combined with CDK4/6 inhibitors.

The purpose of this study was to compare running behaviors, motives, and injury during the first full year of the pandemic compared to the year prior, and month of eased restrictions. 466 runners responded to this follow-up survey. Paired t-tests were used to compare timepoints. Logistic regressions were used to assess demographic influences on behaviors. During the first full year of the pandemic, runners were more likely to increase their weekly runs (Mean Differences [MD]: 0.29±0.10, p < .001), yet had fewer motives (MD: -0.20±0.06, p = .02) compared to the month of eased restrictions. 18-25-year-olds were most likely to increase running volume (Odds Ratio [OR]: 2.79 [1.06, 7.32], p = .04) during the first full year of the pandemic compared to the year prior. Inexperienced runners reported fewer motives (OR: 3.00-4.41, p = .02-.04), and reduced sustained runs (OR: 2.36 [1.13, 4.96], p = .02) during the first full year of the pandemic compared to the year prior. Inexperienced runners and runners who lost access to preferred locations were at increased injury risk (OR: 1.98-2.63, p: .01-.04) during the first full year of the pandemic compared to the year prior. Our findings highlight pandemic-related changes among the running community that are likely to influence behaviors and injury risk.

High-density polyethylene (HDPE) is widely used for above-ground storage tanks (ASTs). However, there are currently no guidelines for the non-destructive testing (NDT) and evaluation (NDE) of HDPE ASTs. Moreover, the feasibility, limitations, and challenges of using NDT techniques for the field inspection of HDPE ASTs have not been well established. This study used both infrared thermography (IRT) and ultrasonic testing (UT) for the field inspection of HDPE ASTs. Highlighting the implementation challenges in the field, this study determined that: (1) ambient environmental parameters can affect IRT accuracy; (2) there is an ideal time during the day to perform IRT; (3) the heating source and infrared camera orientation can affect IRT accuracy; and (4) with proper measures taken, IRT is a promising method for flaw detection in HDPE ASTs. Additionally, UT can be used following IRT for detailed investigation to quantify the size and depth of defects. The manuscript concludes with a discussion of the limitations and best practices for the implementing of IRT and UT for HDPE AST inspections in the field.

The present contribution to the Regional Editors themed issue offers a concise yet focused overview of some of the key technical and scientific issues, as well as of current trends and future challenges, related to the broad discipline of environmental geotechnics in the US region. Particular attention is devoted to current policy and societal drivers as well as future professional and research capacity requirements in critical areas such as innovative recycling and improvement of compost, construction and geologic materials; solid waste management, landfilling and geoenvironmental remediation techniques; and crucial geotechnical engineering aspects of renewable energy production, storage and distribution.

Warming winters due to climate change may critically affect temperate tree species. Insufficiently cold winters are thought to result in fewer viable flower buds and the subsequent development of fewer fruits or nuts, decreasing the yield of an orchard or fecundity of a species. The best existing approximation for a threshold of sufficient cold accumulation, the "chilling requirement" of a species or variety, has been quantified by manipulating or modeling the conditions that result in dormant bud breaking. However, the physiological processes that affect budbreak are not the same as those that determine yield. This study sought to test whether budbreak-based chilling thresholds can reasonably approximate the thresholds that affect yield, particularly regarding the potential impacts of climate change on temperate tree crop yields. County-wide yield records for almond (Prunus dulcis), pistachio (Pistacia vera), and walnut (Juglans regia) in the Central Valley of California were compared with 50 years of weather records. Bayesian nonparametric function estimation was used to model yield potentials at varying amounts of chill accumulation. In almonds, average yields occurred when chill accumulation was close to the budbreak-based chilling requirement. However, in the other two crops, pistachios and walnuts, the best previous estimate of the budbreak-based chilling requirements was 19-32 % higher than the chilling accumulations associated with average or above average yields. This research indicates that physiological processes beyond requirements for budbreak should be considered when estimating chill accumulation thresholds of yield decline and potential impacts of climate change.

Parasites with complex life cycles engaging multiple host species living among different environments well-exemplify the value of a cross-cutting One Health approach to understanding fundamental concerns like disease emergence or spread. Here we provide new information regarding a pathogenic schistosome trematode parasite of both wild and domestic mammals that has recently expanded its known range from mesic/wet environments of the southeastern United States to the arid southwest. In 2018, 12 dogs living near a man-made pond in Moab, Utah, were found positive for Heterobilharzia americana, the most westerly report of this endemic North American schistosome, and the first from Utah. Raccoon scats collected near the pond were positive for H. americana eggs, and snails living near the pond's water line identified as Galba humilis shed H. americana cercariae, the first indication of natural infections in this widespread North American snail species. The susceptibility of G. humilis to H. americana was confirmed experimentally. Our studies support the existence of two variants of H. americana and emphasize the need for further investigations of lymnaeids and their compatibility with H. americana, to better define the future potential for its spread. Capture of a new species of intermediate host vector snail and construction of man-made habitats suitable for this snail have created the potential for a much more widespread animal health problem, especially for dogs and horses. H. americana will prove difficult to control because of the role of raccoons in maintaining transmission and the amphibious habits of the snail hosts of this pathogenic schistosome.

Objectives:. Compare total tumor volume (TTV) response after systemic treatment to Response Evaluation Criteria in Solid Tumors (RECIST1.1) and assess the prognostic value of TTV change and RECIST1.1 for recurrence-free survival (RFS) in patients with colorectal liver-only metastases (CRLM). Background:. RECIST1.1 provides unidimensional criteria to evaluate tumor response to systemic therapy. Those criteria are accepted worldwide but are limited by interobserver variability and ignore potentially valuable information about TTV. Methods:. Patients with initially unresectable CRLM receiving systemic treatment from the randomized, controlled CAIRO5 trial (NCT02162563) were included. TTV response was assessed using software specifically developed together with SAS analytics. Baseline and follow-up computed tomography (CT) scans were used to calculate RECIST1.1 and TTV response to systemic therapy. Different thresholds (10%, 20%, 40%) were used to define response of TTV as no standard currently exists. RFS was assessed in a subgroup of patients with secondarily resectable CRLM after induction treatment. Results:. A total of 420 CT scans comprising 7820 CRLM in 210 patients were evaluated. In 30% to 50% (depending on chosen TTV threshold) of patients, discordance was observed between RECIST1.1 and TTV change. A TTV decrease of >40% was observed in 47 (22%) patients who had stable disease according to RECIST1.1. In 118 patients with secondarily resectable CRLM, RFS was shorter for patients with less than 10% TTV decrease compared with patients with more than 10% TTV decrease (P = 0.015), while RECIST1.1 was not prognostic (P = 0.821). Conclusions:. TTV response assessment shows prognostic potential in the evaluation of systemic therapy response in patients with CRLM.

Introduction: It is reasonable to estimate that tens of millions of men in the United States played high school football. There is societal concern that participation in football confers risk for later-in-life mental health problems. The purpose of this study is to examine whether there is an association between a personal history of playing high school football and death by suicide.Methods: The subjects were obtained from the Lieber Institute for Brain Development (LIBD) brain donation program in collaboration with the Office of the Medical Examiner at Western Michigan University Homer Stryker MD School of Medicine. Donor history was documented via medical records, mental health records, and telephone interviews with the next-of-kin.Results: The sample included 198 men aged 50 or older (median = 65.0 years, interquartile range = 57–75). There were 34.8% who participated in contact sports during high school (including football), and 29.8% participated in high school football. Approximately one-third of the sample had suicide as their manner of death (34.8%). There was no statistically significant difference in the proportions of suicide as a manner of death among those men with a personal history of playing football compared to men who did not play football or who did not play sports (p = 0.070, Odds Ratio, OR = 0.537). Those who played football were significantly less likely to have a lifetime history of a suicide attempt (p = 0.012, OR = 0.352). Men with mood disorders (p < 0.001, OR = 10.712), substance use disorders (p < 0.020, OR = 2.075), and those with a history of suicide ideation (p < 0.001, OR = 8.038) or attempts (p < 0.001, OR = 40.634) were more likely to have suicide as a manner of death. Moreover, those men with a family history of suicide were more likely to have prior suicide attempts (p = 0.031, OR = 2.153) and to have completed suicide (p = 0.001, OR = 2.927).Discussion: Suicide was related to well-established risk factors such as a personal history of a mood disorder, substance abuse disorder, prior suicide ideation, suicide attempts, and a family history of suicide attempts. This study adds to a steadily growing body of evidence suggesting that playing high school football is not associated with increased risk for suicidality or suicide during adulthood.

OBJECTIVES:. To evaluate the implementation of a pediatric sepsis pathway in the emergency department as part of a statewide quality improvement initiative in Queensland, Australia. DESIGN:. Multicenter observational prospective cohort study. SETTING:. Twelve emergency departments in Queensland, Australia. PATIENTS:. Children less than 18 years evaluated for sepsis in the emergency department. Patients with signs of shock, nonshocked patients with signs of organ dysfunction, and patients without organ dysfunction were assessed. INTERVENTIONS:. Introduction of a pediatric sepsis pathway. MEASUREMENTS AND MAIN RESULTS:. Process measures included compliance with and timeliness of the sepsis bundle, and bundle components. Process and outcome measures of children admitted to the ICU with sepsis were compared with a baseline cohort. Five-hundred twenty-three children were treated for sepsis including 291 with suspected sepsis without organ dysfunction, 86 with sepsis-associated organ dysfunction, and 146 with septic shock. Twenty-four (5%) were admitted to ICU, and three (1%) died. The median time from sepsis recognition to bundle commencement for children with septic shock was 56 minutes (interquartile range, 36–99 min) and 47 minutes (interquartile range, 34–76 min) for children with sepsis-associated organ dysfunction without shock; 30% (n = 44) and 40% (n = 34), respectively, received the bundle within the target timeframe. In comparison with the baseline ICU cohort, bundle compliance improved from 27% (n = 45) to 58% (n = 14) within 60 minutes of recognition and from 47% (n = 78/167) to 75% (n = 18) within 180 minutes of recognition (p < 0.05). CONCLUSIONS:. Our findings on the introduction of protocolized care in a large and diverse state demonstrate ongoing variability in sepsis bundle compliance. Although bundle compliance improved compared with a baseline cohort, continued efforts are required to ensure guideline targets and sustainability are achieved.

The present study employed a quasi-experimental design to assess a computer-based tool, which was intended to scaffold the task of designing experiments when using a virtual lab for the process of experimentation. In particular, we assessed the impact of this tool on primary school students' cognitive processes and inquiry skills before and after the study's treatment, using pre- and post-tests. Our research design involved a group of students who used the computer-based tool/scaffold to design the study's experiments (experimental condition) and a group of students who used a paper-and-pencil worksheet as a scaffold to design the same experiments (control condition). The primary finding of the study was that the use of the computer-based experiment design tool had a more positive effect on students' inquiry skills related to identifying variables and designing investigations than the paper-and-pencil one. This might be attributed to the functionalities provided only by the computer-based experiment design tool, which enabled students to focus their attention on crucial aspects of the task of designing experiments through (1) maintaining values for constant variables when planning experimental trials and (2) the provision of instant feedback when classifying variables into independent, dependent and controlled variables. Moreover, students in the two conditions displayed differing patterns of interactions among cognitive process and inquiry skills. Implications for designing and assessing similar computer-based scaffolds are discussed.

Understanding the strain transfer mechanism is required to interpret strain sensing results for fiber optic cables. The strain transfer mechanism for fiber optic cables embedded in cementitious materials has yet to be thoroughly investigated experimentally. Interpretation of fiber optic sensing results is of particular concern when there is a displacement discontinuity. This study investigates the strain transfer mechanism for different types of fiber optic cables while embedded in concrete cubes, sustaining a boundary condition which features a displacement discontinuity. The strain transfer mechanisms for different cables are compared under increasing strain levels. Under cyclic loading, the nonlinear behavior of the force–displacement relation and of the strain distribution in the fiber optic cable are discussed. The mechanical properties of the fiber optic cables are presented and discussed. A parameter is proposed to quantify the strain transfer length. The results of this study will assist researchers and engineers to select appropriate cables for strain sensing and interpret the fiber optic sensing results.

Mass spectrometry (MS)-based techniques, including liquid chromatography coupling, shotgun lipidomics, MS imaging, and ion mobility, are widely used to analyze lipids. However, with enhanced separation capacity and an optimized chemical derivatization approach, comprehensive two-dimensional gas chromatography (GC×GC) can be a powerful tool to investigate some groups of small lipids in the framework of lipidomics. This study describes the optimization of a dedicated two-stage derivatization and extraction process to analyze different saturated and unsaturated fatty acids in plasma by two-dimensional gas chromatography–time-of-flight mass spectrometry (GC×GC–TOFMS) using a full factorial design. The optimized condition has a composite desirability of 0.9159. This optimized sample preparation and chromatographic condition were implemented to differentiate between positive (BT) and negative (UT) boar-tainted pigs based on fatty acid profiling in pig serum using GC×GC–TOFMS. A chemometric screening, including unsupervised (PCA, HCA) and supervised analysis (PLS–DA), as well as univariate analysis (volcano plot), was performed. The results suggested that the concentration of PUFA ω-6 and cholesterol derivatives were significantly increased in BT pigs, whereas SFA and PUFA ω-3 concentrations were increased in UT pigs. The metabolic pathway and quantitative enrichment analysis suggest the significant involvement of linolenic acid metabolism.

The authors contend that the impact of the Cold War on multilateral organizations (especially UNESCO) as well as on the academic programs in Comparative and International Education or Development Studies in Education has been largely understudied. Both world-systems (USA and its allies, Soviet Union and its allies) laid claim on the project of world peace that UNESCO was meant to pursue. Furthermore, the boom in area, language and development studies in the 1960s was closely associated with the international race between the two world-systems over the patronage of those postcolonial countries that were viewed as "non-aligned" or neutralist. The salutary effects upon education policy in the United States are described, along with the portrayal of education as an inferior aspect of the capitalist system, behind the "iron curtain." The authors note the new research field of post-Cold War studies that emerged in U.S. academe over the past decade, and find that such studies are surprisingly scarce in comparative and international education which, by virtue of analyzing other educational systems, was at the center of the dichotomy.

For well over a century, there have been boarding schools for American Indian children. The unique configuration that makes up each boarding school's environment attempts to meet the needs of as many students as possible, and tries to maximize positive outcomes. Recognizing that there is room for improvement, the Office of Indian Education Programs (OIEP) provided several years of funding to a group of schools in order to enhance their services to children. The selected boarding schools were provided Therapeutic Residential Model (TRM) funding to carry out their proposals. To determine each site's accomplishments as well as the efficacy of this approach, the OIEP concurrently implemented a cross-site evaluation. The evaluation was designed to: (1) provide a record and evaluation of the characteristics of each site's environment prior to funding; (2) document the course of planning and implementation of changes during TRM funding; (3) collect data on incoming students and outcome data agreed upon by all sites; (4) provide ongoing analysis of the data to the sites so that administrators could make program changes; and (5) use process and outcome data from these diverse sites to draw cross-site conclusions. In this article, the authors discuss the results of a cross-site evaluation which is patterned on chaos theory. Data were collected in the course of complex changes occurring in systems. Also, staff and student surveys provided the basis for data comparison among boarding schools. Furthermore, this article is divided into four sections including: (1) the identification of the factors that were common to sites that achieved high retention, and it describes the prevailing situation at those sites that were not successful at retaining students; (2) the examination of the process and outcome indicators that presumably impacted the retention rate at each TRM site; (3) the examination of each boarding school's ability to establish a data feedback loop to guide dynamic system change; and (4) is entitled Elephants in the Living Room, and deals with common issues across sites. The survey data indicated that students coming into the boarding school or peripheral dormitory sites had similar risk factors. (Contains 1 table and 24 figures.)

At the No Treatment Day School, less than 15% of students used the dormitory during the school week. Located in the heart of a reservation and serving local students, the K-12 school enrolled over 1,000 students. The site received Therapeutic Residential Model funding for the 2001-2002 school year. Initial evaluation of this site found an array of daunting problems throughout the school structure and functioning. There were some successes, including implementation of the Morningside reading program in the elementary school and some response from the community to the comprehensive evaluation report which provided an overview of the situation to policy-makers and community members. However instability in the system and a mid-year change in leadership complicated the process of implementation. By the end of the first year, it was clear that the feasibility of the original proposal was questionable and that an overhaul of he school's system and culture was necessary before a Therapeutic Residential Model could be implemented or significant change could come about. Therapeutic Residential Model funding was terminated at the end of the school year. As there was no substantial implementation of a Therapeutic Residential Model program, data gathered were utilized as representing a naturally occurring control or minimal treatment site. (Contains 8 tables and 16 figures.)

This off-reservation boarding school serves over 600 students in grades 4-12; approximately 85% of the students reside in campus dormitories. After having documented significant improvement on a number of outcomes during a previous High Risk Youth Prevention demonstration grant, the site submitted a Therapeutic Residential Model proposal, requesting funding to continue successful elements developed under the demonstration grant and to expand mental health services. The site received Therapeutic Residential Model funding for school year 2001-2002. Once funds were received, the site chose to shift Therapeutic Residential Model funds to an intensive academic enhancement effort. While not in compliance with the Therapeutic Residential Model initiative and therefore not funded in subsequent years, this site created the opportunity to enhance the research design by providing a naturally occurring placebo condition at a site with extensive cross-sectional data baselines that addressed issues related to current federal educational policies. (Contains 4 tables, 31 figures and 1 footnote.)

L3 is an intertribal residential school enrolling approximately 200 students in grades 5-8 from tribes in the northern Midwest. As a result of successful grant-writing which espoused Circle of Courage and Asset-Building, the school built up an impressive configuration of programs funded by a variety of sources, including a cadre of mental health professionals, and began increasingly to rely on their assessments and services. First funded by the Therapeutic Residential Model program in the 2002-2003 school year, L3 used the funding that year primarily to increase professional-level services of a psychiatrist and psychologist, and to maintain or expand programs which would otherwise have been terminated as funding from short-term sources was running out. Evaluation of this project began in January 2003, when the site was assessed and determined to be strongly oriented toward provision of Level Three, or professional-level, psychiatric and medical mental health services. The initial evaluation report identified a low retention rate and raised concerns that the presence of more than 200 staff on campus had resulted in a diffusion of responsibility, lack of consistency, and duplication or redundancy of services; that elements of the environment appeared to be detrimental to social development and emotional stability; and that an unusually high proportion of students were receiving psychiatric diagnoses and medication. The site was asked to address these issues, and additional funding was provided to bolster lower levels of triage by adding paraprofessional case managers to advocate or students and coordinate provision of services for them. Retention remained low at this site throughout the course of funding, and there were a high number of assaults and psychiatric hospitalizations compared with other sites. (Contains 14 tables and 11 figures.)

The purpose of the therapeutic model demonstration schools is: (1) to provide a program, based on an annual written plan, linking clinicians, counselors, and mental health professionals with academic program personnel in a culturally sensitive residential program tailored to the particular needs of Indian students; (2) to provide for a continued evaluation of the planning and implementation of the therapeutic model in the designated schools; and (3) to determine what steps the Bureau of Indian Affairs must take and what resources are required to transform existing off-reservation boarding schools to meet the needs of chemically dependent, emotionally disturbed, socially troubled or other at-risk Indian youth who attend such schools." The articles in this issue describe each of the sites which were funded during the Therapeutic Residential Model (TRM) initiative. The methodology used for the cross-site evaluation is described in this introductory article. The next five articles provide case studies of each site and vary in format and analysis of the data governed by environmental factors found at each site, the nature of problems identified and addressed by each system, and level of statistical power determined by sample sizes. Case studies of L1, L2, and L3, the sites funded for multiple years, include contributions from both the cross-site and internal site evaluations. The case study of Academic Enhancement (AE) is enhanced by data gathered in the course of a multiyear prevention demonstration project which had preceded TRM funding and had laid the groundwork for change at this site. The final article draws conclusions across sites, and discusses both best practices and barriers to success found in these sites. A Staff Survey is appended. (Contains 4 figures and 3 tables.)

This site is an intertribal residential grant school annually enrolling over 250 students in grades 1-8 from tribes located in three states on the Northern Great Plains. From its inception in 1890, the boarding school's mission has been to provide services for young children in need of a safe and supportive living and learning environment. For over a decade, this site has used strategies centered on respecting children, structuring students' time, and providing the therapeutic benefits of a well-maintained campus. This site also has a long history of believing in each child's inherent value and potential. When Therapeutic Residential Model funding commenced at the midpoint of the 2002-2003 school year, L1 focused these new resources on strengthening and refining its program. The number of personnel positions increased from 98 to 135, with new positions principally going to dormitory staff and four Masters-level counselor positions. This increase in staff allowed L1 to proactively address the children's developmental needs. The site also adopted and implemented the Applied Humanism caregiving model. In accordance with Applied Humanism, an interview was utilized that allowed the site to identify and hire applicants possessing the attitudes and skills necessary to be good caregivers, existing staff were trained so that they understood the kind of caregiving that would be expected of them, supervision procedures and practices were implemented that supported and encouraged good caregivers and provided time-limited assistance to those who were not, and relevant agency policies and procedures were revised as needed to align with the Applied Humanism philosophy. In addition, the Morningside program was brought in to systematically address the students' academic lags in reading. The results of implementing the Therapeutic Residential Model were a reduction in behavioral incidents, a decrease in the amount of money spent on external mental health services, an increase in the retention rate, an increase in academic skills in selected areas, and higher scores on pre-post measures of adjustment, interpersonal relationships, and adaptability. (Contains 16 tables and 19 figures.)