cssi/SciSciGPT-SciSciNet huggingface dataset:
Sirolimus therapy and follow-up in a patient with severe congenital hyperinsulinism following subtotal pancreatectomy

Congenital hyperinsulinism (CHI) is the most common cause of severe, persistent hypoglycemia in neonates and infants. Current available treatment is subtotal pancreatectomy if the patient does not respond to medical treatment but some of the patients still experience severe hypoglycemia after the surgery. Sirolimus, a mammalian target of rapamycin(mTOR) inhibitor recently has been reported to be effective in the treatment of insulinoma and CHI patients. Here we report a patient with CHI who had prolonged hypoglycemia after the subtotal pancreatectomy. The patient with a heterozygous mutation in ABCC8 was unresponsive to optimal dose of diazoxide (15 mg/kg/day) and octreotide (30µg/kg/day). The patient subsequently had subtotal pancreatectomy; however, the patient continued to have severe and persistent hypoglycemia. Sirolimus was commenced. Glycemic control had remarkable improvement without major adverse events, although he required a small dose of octreotide to maintain euglycemia. Sirolimus therapy was discontinued when the patient was 15 months old. The patient had been having a good glycemic control at the time of this report when he was three years and 8 months old. This report suggests that sirolimus may be an effective treatment option in patients with CHI resistant to traditional medical therapy or failure of subtotal pancreatectomy. However, the long-term safety needs to be studied in larger group of very young patients.
Through the Agency of Words: Women in the American Insane Asylum, 1842–1890

Between 1842 and 1890, 23 women wrote 33 memoirs about their time spent incarcerated in American insane asylums. While a handful of these memoirs have been studied, there has not been a recognition of how many asylum mem­oirs exist and their significance as a collective body of work. Grounded in an inductive analysis of the collective 33 works, this article begins a process of recovering a mostly forgotten moment in time when former patients took agency over their experience, ethos, and rhetoricity to break down the institutional wall of silence and give the public the first patient-centered memoirs. I argue that these women rhetors did this by foregrounding their own identity as patient and by creating a rhetorical position from which their readers would feel the trauma of asylum life. Both rhetorical moves countered institutionalization’s dehumanizing effects by placing the patient experience at the center of understanding the asy­lum experience.
NON-INVASIVE CEREBRAL OXYGENATION (RSO2) DURING MILD THERAPEUTIC HYPOTHERMIA AND REWARMING

Background Multi-centered studies in adults who were kept hypothermic as brain protective strategy after cardiac arrest and also in newborn babies with perinatal asphyxia have clearly demonstrated that mild hypothermia (32 to 34 degrees C) can improve neurological outcome after post-anoxic injury. This represents a highly promising development in the field of neurocritical care. Methods Observational study during mild therapeutic hypothermia and rewarming post resuscitation. We induced a rectal temperature of 32 to 34 degrees C for 24 to 48 hours, after which we rewarmed +0,5 degrees C per 2 hours. Real-time regional oxygenation, right and left cerebral cortex of the watershed region, was measured with the INVOS 5100 continuously. Results 7 patients were measured; 1 patient had a lack of data. Of the 6 remaining patients; 2 patients died, 4 survived. We evaluated the correlation between the mean cerebral oxygen saturation with the temperature of the patient; The survivors had a positive correlation (min.0,561- max. 0,829/ resp. p = 0.007- 0,000) versus the deceased who had a negative correlation (−0,634 and −0,497/ resp p = 0.02 and 0.01). Conclusions We found a negative versus a positive correlation between cerebral oxygenation and temperature of the patient in resp. deceased patients versus survivors after resuscitation. This suggests an increase of cerebral oxygen supply in survivors during an increasing temperature. Confirmative data will reveal the predictive value for survival of routine rSO2.
Activation of MAPK and AKT pathways by BRAF, NRAS and PIK3CA mutations in melanoma

155 Malignant melanoma is an aggressive tumor of the skin with a poor prognosis for patients with advanced disease. It is resistant to current therapeutic approaches. In melanoma, both the Ras-Raf-MEK-ERK (MAPK) and the PI3K-AKT (AKT) signaling pathways are constitutively activated through multiple mechanisms. Mutation of BRAF has been proposed to contribute to melanoma development. Increased activity of the MAPK pathway prevents apoptosis and induces cell cycle progression. V600E accounts for more than 90% of BRAF mutations in melanoma. This mutation causes a substantial increase in B-Raf kinase activity. Moreover, an interaction has been recently found (Tsao et al, J. Invest. Dermatology, 2004) between the MAPK and the PI3K/AKT pathways, both activated in cutaneous melanoma. Interestingly, these studies suggest that MAPK and AKT pathways are activated in parallel. The mechanism by which AKT is activated remains unknown. Recently, mutations of PIK3CA gene have been identified in different human cancers. We screened tumor biopsy specimens from 68 patients with melanoma for PIK3CA mutations to determine whether or not PIK3CA plays a role in melanoma development. Mutations of BRAF and NRAS were also analyzed in the same tumor specimens. Activation of either the MAPK or AKT pathways were investigated by immunohistochemistry (IHC) in melanoma tissues. BRAF mutations were detected in 43 of 68 melanoma patients (61%). NRAS mutations were identified in 17 of 68 (25%) melanoma patients, while PIK3CA gene was mutated in 5 of 68 (7%) of tumor samples. In agreement with previous data, BRAF mutations occur exclusively in melanomas that were wild type for NRAS. Interestingly, one tumor sample harbouring a PIK3CA mutation was also mutated at BRAF. A total of 65/68 (95%) melanomas were mutated at BRAF, NRAS or PIK3CA. The MAPK and AKT pathways were activated in all samples having gene mutations. However, only the AKT pathway was highly expressed in the tumor tissue with both PIK3CA and BRAF mutations. These findings may explain why the AKT pathway plays an important role in melanoma development. Some PIK3CA mutations may block the MAPK pathway by activating AKT which phosphorylates and inactivates Raf. This may alter the terminal differentiation capacity of the cells. The results of the present study indicate that in melanoma both the MAPK and the AKT signaling pathways play pathogenic roles and may represent promising therapeutic targets for an otherwise devastating disease.
Do male and female adolescents report symptoms differently after concussion

We investigated sex-based differences in the presence and severity of aggregated symptom indicators as well as individual concussion symptoms.Materials and Methods: A cross-sectional examination of sex differences in symptoms reported by adolescents upon initial concussion evaluation at a concussion clinic. Nine hundred and eighty-six adolescents completed the Sport Concussion Assessment Tool (SCAT5) symptom checklist. Chi-square and Mann-Whitney U tests were used for differences in the presence and severity of symptoms, respectively. Sex differences in global indices of symptom distress were compared.Results: Females endorsed more symptoms (Female: Median (M)=15, Interquartile range (IQR):9-18 vs. Male: M=11, IQR: 6-15, p<0.001) and a greater total symptom score (Female: M=37, IQR:16-45 vs. Male: M=20, IQR:8-39). After False Discovery Rate (FDR) adjustment, females endorsed the presence of 21 of 22 individual symptoms more frequently than males (p≤ 0.039), with greater symptom severity for 20 of 22 individual symptoms (p≤0.036). Moderate ESs were observed for sex-based differences in the total symptom score and the global severity index. Small ESs was observed for differences in most individual symptoms.Conclusions: The greater frequency and severity of concussion symptoms reported by female adolescents highlights the importance of considering sex as a modifier for the management of concussion.
Content analysis of promotional material for asthma-related products and therapies on Instagram.

Increasingly, social media is a source for information about health and disease self-management. We conducted a content analysis of promotional asthma-related posts on Instagram to understand whether promoted products and services are consistent with the recommendations found in the Global Initiative for Asthma (GINA) 2019 guidelines. We collected every Instagram post incorporating a common, asthma-related hashtag between September 29, 2019 and October 5, 2019. Of these 2936 collected posts, we analyzed a random sample of 266, of which, 211 met our inclusion criteria. Using an inductive, qualitative approach, we categorized the promotional posts and compared each post’s content with the recommendations contained in the 2019 GINA guidelines. Posts were categorized as “consistent with GINA” if the content was supported by the GINA guidelines. Posts that promoted content that was not recommended by or was unrelated to the guidelines were categorized as “not supported by GINA”. Of 211 posts, 89 (42.2%) were promotional in nature. Of these, a total of 29 (32.6%) were categorized as being consistent with GINA guidelines. The majority of posts were not supported by the guidelines. Forty-one (46.1%) posts promoted content that was not recommended by the current guidelines. Nineteen (21.3%) posts promoted content that was unrelated to the guidelines. The majority of unsupported content promoted non-pharmacological therapies (n = 39, 65%) to manage asthma, such as black seed oil, salt-room therapy, or cupping. The majority of Instagram posts in our sample promoted products or services that were not supported by GINA guidelines. These findings suggest a need for providers to discuss online health information with patients and highlight an opportunity for providers and social media companies to promote evidence-based asthma treatments and self-management advice online.
Tibial alignment following intramedullary nailing via three approaches.

The purpose of this study is to evaluate the incidence of malalignment in patients undergoing IMN for tibial shaft fractures treated with the extra-articular lateral parapatellar, suprapatellar, and infrapatellar approaches. A retrospective review of an institutional trauma database was completed at a single level 1 trauma academic medical centre. Quality of reduction was assessed using the following three parameters: (1) 5 mm displacement, 1 > 5 mm gapping), 4 infrapatellar (4 > 5 mm displacement), and 3 lateral extra-articular parapatellar (2 > 5 mm displacement and 1 > 5 mm gapping). No reductions were determined to be bad according the Baumgaertner et al. criteria. There was no significant difference in the rate of combined fibula fractures or the rate of fibular fixation between the three cohorts. In conclusion, no significant difference was found in fracture reduction angulation, displacement, and gapping in patients treated with an IMN with respect to approach for diaphyseal or metadiaphyseal tibial shaft fractures.
What Motivates Us to Go on Strike? Social and Moral Norms and their Impact on Strike Participation in Individualist and Collectivist Situations in Western Cultures

Collective action such as strikes is important for sociopolitical expression. The current study explored cross-cultural differences in the psychology of strikes through an adapted version of the Theory of Planned Behavior (TPB) model. Our model incorporates personal and social-level psychological processes that motivate strike participation and we explored how cultural values and normative nudges moderate these processes. French and American participants received social or moral nudge messages and indicated their intentions to participate in a hypothetical strike. We successfully replicated parts of the TPB model and found that culture and nudge type moderated the relationship between personal attitudes and strike intentions. Our findings highlight the multi-level motivation for and context-sensitive cultural influence on collective action.
Indian Trappers and the Hudson's Bay Company: Early Means of Negotiation in the Canadian Fur Trade

The fur trade and arrival of the Hudson's Bay Company had numerous effects on northern North American indigenous populations. One such group is the Gwich'in Indians in the northwestern portion of the Northwest Territories. Aside from disease and continued reliance on goods imported from the south, the fur trade disrupted previous economic relationships between indigenous groups. In some examples, the presence of the Hudson's Bay Company furthered tension between indigenous groups as each vied for the control of fur-rich regions and sole access to specific Company posts. However, due to the frontier nature of the Canadian north, the relations between fur trade companies and indigenous peoples was one of mutual accommodation. This was in stark contrast to other European-Indian relations. This paper examines how credit relations between the Hudson's Bay Company and the Gwich'in reveals a model of resistance.
Exploiting Symmetries Alternating Sign Matrices and the Weyl Character Formulas

This paper illustrates some of the power and beauty of determinantevaluations, beginning with Cauchy’s proof of the Vandermondedeterminant evaluation, continuing through the Weyldenominator formulas and some open conjectures on alternating-sign{matrices}, and ending with the Izergin–Korepin determinantexpansion for the six-vertex model with domain wall boundaryconditions.
Kuchiki, A. and Tsuji, M.: Industrial clusters in Asia: analysis of their competition and cooperation

Industrial clusters have become a very important topic in international economic and business studies. However, there has not been much literature in English on industrial clusters in Asia. Therefore, this book, edited by Kuchiki and Tsuji, is a welcome volume that adds Asian cases to regional science. The book is the result of the teamwork by scholars from the United States, China and Japan. Both editors were involved in an earlier book (published in 2003) on industrial clusters in the United States, Italy and Asia, which was also coordinated and funded by the Institute of Developing Economies, Japan External Trade Organization. In this book, the authors examine industrial clusters in Vietnam, China, Malaysia, India and Japan. Other than Bangalore, which has been one of the most famous software industrial clusters in the world, almost all the other clusters covered in this book are not well known. The authors study how industrial clustering or agglomeration occurs in the development of certain Asian economies and how the agglomeration forges competition and cooperation among firms. The book is divided into three parts: Part I (Chap. 2) is written by the U.S. team. This part examines Vietnam as a case study, applying the geographic information systems (GIS) approach. The authors find that there are some signs of agglomeration in Vietnam. However, advanced clusters, such as those in the USA and Japan, have not yet emerged. A key finding is that the rise of private enterprises as a result of economic reform is critical to the formation of industrial clusters. The reform provides an environment that is conducive to private firms. The authors also noted that Vietnam has a strong foundation with its existing network of business associations, cooperatives and
Regional trends in active diapirism revealed by mountain range‐scale InSAR time series

[1] We construct an orogen-wide InSAR time series over the Zagros Mountains and eastern Markan Subduction Zone in southern Iran from 19 Envisat tracks spanning 2003–2010. We observe active salt diapirism of the infra-Cambrian Hormuz Salt at 20 locations and identify several diapirs that are not moving. All active diapirs reach the surface within the Asmari Limestone or older rock units while we do not observe any active diapirism occurring within younger exposures, reflecting a complex vertical accumulation of the basal salt and reactivation of diapirs by erosion. Diapir reactivation of this sort may be a critical factor affecting the feasibility of sequestering nuclear waste and CO2 in evaporite sequences over geologic time scales. The distribution of active diapirism is indifferent to increases in mean elevation, suggesting a relatively uniform thickness of the Zagros Fold Belt above the basal salt with steps in topography driven by basement thickening. We do not observe aseismic uplift of anticlines because rates are likely below the detection threshold of our time series. This suggests that uplift is accommodated at small rates (<2–3 mm/yr) over numerous structures instead of focused at the deformation front.
ML-PDA track validation thresholds

The maximum likelihood probabilistic data association (ML-PDA) algorithm, developed for very low observable (VLO) target tracking, will always provide a candidate track that must then be either validated or rejected. By comparing the value of the log likelihood ratio (LLR) at the parameter estimate to a threshold value, track validation is accomplished. Using extreme value theory, we show that in the absence of a target the LLR global maximum obeys approximately a Gumbel distribution and not the Gaussian distribution previously ascribed to it in the literature. It is shown that the Gaussian approximation yields inaccurate false track acceptance probabilities. Using a Gumbel distribution, the probability of false track rejection can be obtained for a given threshold value. The probability of true track detection is obtained assuming the LLR global maximum obeys approximately a Gaussian distribution in the presence of a target. A system operating characteristic (SOC) is developed that unifies the detection processing and track algorithm performance into a single performance metric. The performance of this test is demonstrated through simulations.
Trends in Exposure to Chemicals in Personal Care and Consumer Products

Synthetic organic chemicals can be used in personal care and consumer products. Data on potential human health effects of these chemicals are limited-sometimes even contradictory-but because several of these chemicals are toxic in experimental animals, alternative compounds are entering consumer markets. Nevertheless, limited information exists on consequent exposure trends to both the original chemicals and their replacements. Biomonitoring (measuring concentrations of chemicals or their metabolites in people) provides invaluable information for exposure assessment. We use phthalates and bisphenol A-known industrial chemicals-and organophosphate insecticides as case studies to show exposure trends to these chemicals and their replacements (e.g., other phthalates, non-phthalate plasticizers, various bisphenols, pyrethroid insecticides) among the US general population. We compare US trends to national trends from Canada and Germany. Exposure to the original compounds is still prevalent among these general populations, but exposures to alternative chemicals may be increasing.
Pancreatic carboxypeptidase hydrolysis of bile acid-amino acid conjugates: Selective resistance of glycine and taurine amidates

To find a possible explanation for the selective hepatic conjugation of bile acids with glycine or taurine, the N-acyl amidates of cholic acid and a number of amino acids and amino acid analogues were synthesized, and their susceptibility to hydrolysis by pancreatic juice, gastric juice, serum, or small intestinal mucosal enzymes was measured. Deconjugation by pure carboxypeptidase A and B was also examined, and hydrolysis by these tissue fluids and enzymes was compared with that mediated by a bacterial cholylglycine hydrolase. Human pancreatic juice efficiently hydrolyzed cholyl conjugates of all neutral-L-amino acids (cholyl-L-alanine, cholyl-L-valine, cholyl-L-leucine, and cholyl-L-tyrosine), except cholylglycine. The net hourly rate of hydrolysis (in micromoles per milligram protein per hour) increased when the terminal residue was aromatic or branched aliphatic, and appeared to be specific for L-alpha-amino acids as cholyl-beta-alanine and cholyl-D-valine were not cleaved. From cholyl glycylglycine, only the terminal glycine was efficiently removed. Cholyltaurine and cholyl conjugates with the methyl and propyl analogues of taurine were resistant to hydrolysis. Two basic amino acid conjugates (cholyl-L-lysine and cholyl-L-arginine) were cleaved, whereas conjugates of acidic amino acids (cholyl-aspartate and cholyl-cysteate) were not cleaved. Studies using pure enzymes showed that bovine carboxypeptidase A hydrolyzed the cholyl conjugates of the neutral L-alpha-amino acids with similar specificity as observed for the human pancreatic juice, whereas bovine carboxypeptidase B cleaved the basic amino acid conjugates. Cholyl-L-lysine and cholyl-L-arginine were also cleaved by serum and plasma, which are known to possess carboxypeptidase activity. Cholyl conjugates were not cleaved by gastric juice, by trypsin, or by homogenates of rat small intestinal mucosa. In contrast, all cholyl conjugates were cleaved by a bacterial cholylglycine hydrolase. These experiments indicate that glycine and taurine amidates of cholic acid differ from a number of other conjugates with neutral and basic amino acid in being resistant to hydrolysis by pancreatic and plasma carboxypeptidases.(ABSTRACT TRUNCATED AT 400 WORDS)
Mathematics Journals Should Be Electronic and Free

Many important journal functions would be lost if the mathematical community replaced all paper journals with electronic media. Electronic media are useful for some purposes, but they will not be the basis for a publishing revolution in the near future.
Smart Schools: From Training Memories to Educating Minds

In response to the crisis in American education, Perkins examines the ways in which children learn and think. He shows how current teaching methods leave children with a flimsy grasp of what they are taught, and suggests strategies for deepening knowledge and stimulating independent thought.
Lipid encapsulation of arsenic trioxide attenuates cytotoxicity and allows for controlled anticancer drug release.

Arsenic trioxide (ATO, As2O3) is emerging as a front line agent for treatment of acute promyelocytic leukemia with giving a complete remission rate of 83−95%. ATO also shows significant activity in relapsed/refactory multiple myeloma; however, efforts to expand clinical utility to other cancers have been limited by its toxicity profile at higher doses. New bioavailable, liposome encapsulated As(III) materials exhibit a significantly attenuated cytotoxicity that undergoes pH-triggered release of an active drug. The arsenic drugs are loaded into 100-nm-scale liposomes at high concentration (>270 mM) and excellent retention (shelf life > 6 months at 4 °C), as determined by inductively coupled plasma optical emission spectroscopy (ICP−OES), transmission electron microscopy (TEM), and energy-dispersive X-ray (EDX) diffraction. In the loading mechanism, arsenous acid crosses the bilayer membrane in exchange for acetic acid and an insoluble transitional metal (e.g., Ni2+, Co2+) arsenite salt is formed. The resul...
Primary Prevention of Alcohol Misuse: Overview and Annotated Bibliography

Following an overview of conceptual and methodological issues related to alcohol misuse primary prevention and a brief discussion of the most frequently employed primary prevention strategies, a comprehensive annotated bibliography of the alcohol misuse primary prevention literature is presented. Several benefits of presenting detailed annotations, such as allowing readers to (a) examine the various prevention program components, (b) identify the presence or absence of methodological shortcomings, (c) identify whether or not high-risk groups were included as program participants, and (d) evaluate the feasibility of program implementation, are also highlighted. The present article complements previous reviews which have often mixed together the findings of primary and secondary prevention studies and which have typically reported the effects of prevention programming on multiple substance misuse outcomes simultaneously. The practice of simultaneously reporting multiple substance misuse outcomes has made it difficult to interpret the specific effects that primary prevention programs have had on alcohol misuse per se.
Disseminated intravascular coagulation and hemorrhage in hemophilia B following elective surgery

Two patients with hemophilia B are described in whom disseminated intravascular coagulation (DIC) developed following infusion of repeated doses of Factor IX concentrate in the perioperative period. In both cases the surgery was elective, Factor IX survival studies had been done to assure proper dosing, and Factor IX levels were monitored daily. Neither patient had clinically significant liver disease. The DIC manifested itself as excessive blood loss from surgical drains without documented thrombosis and was accompanied by prolonged coagulation times, increased fibrin split products and decreased fibrinogen and platelets. In both patients the process was quickly reversed with administration of fresh frozen plasma, cryoprecipitate, and the addition of heparin to the Factor IX concentrate. These cases highlight the difficulty in managing patients with hemophilia B undergoing surgical procedures due to the potential thrombogenicity of the currently available concentrates, and the importance of differentiating the bleeding associated with DIC from underdosing with Factor IX. Furthermore, the potential complications associated with the presently available Factor IX concentrates stress the need for the development of purer, safer Factor IX concentrates.
Permutation procedures with censored data

This paper extends the permutation procedures for truncated data in Diaconis et al. (http://www-stat.stanford.edu/~susan/.) to doubly censored data. As in Diaconis et al. (http://www-stat.stanford.edu/~susan/.), the proposed procedure is based on samples from the conditional distribution of rank statistics which is uniformly distributed on a set of permutations. Subsequently, our procedure is applied to testing independence with bivariate censored data and estimating a regression coefficient with doubly censored data. Also, when estimating a regression coefficient with doubly censored data, simulation studies show that the proposed procedure is superior to that of Akritas et al. (J. Amer. Statist. Assoc. 90 (1995) 170).
Interpretation of hydrogen chemisorption on nickel catalysts

Abstract The origin of reversible hydrogen adsorption on dispersed nickel catalysts has been examined through analysis of in situ magnetization and chemisorption measurements on a large number of silica- and alumina-supported catalysts. Parameters considered were crystallite size, extent of reduction, calculated surface capacity, NM, measured surface capacity for irreversible adsorption, N0, slope of the reversible isotherm, b, and surface accessibility, N 0 N M . Relationships between experimental variables were used to rule out certain models explaining reversible adsorption and to support others. Adsorption on the support, spillover, reaction with unreduced nickel compounds, and surface contamination were eliminated from considerations as inconsistent with observed magnetic responses. Site heterogeneity within the monolayer was considered unlikely from temperature dependence and other factors. The most significant effect was a correlation between the degree of accessibility and the areal slope b N 0 showing that the amount of reversible adsorption increased as surface accessibility decreased. This minimized consideration of multilayer adsorption on subsurface sites and diffusion into the bulk of the crystallite but reenforced the concept of diffusion into the inaccessible region of the surface. Extrapolation of hydrogen adsorption isotherms to zero pressure is recommended as the best method for measuring exposed surface.
U.S. regional impacts of climate change

On 4 December, the Pew Center on Global Climate Change released a report that assesses climate vulnerabilities in four different areas of the United States. “Regional impacts of climate change: Four case studies in the United States” notes that midwestern cities are likely to experience more frequent, longer, and hotter heat waves; that wildfires are likely to increase in the U.S. West; that sustaining fragile Gulf Coast wetlands ecosystems will be increasingly difficult due to climate change; and that the Chesapeake Bay may respond to climate change with more frequent and larger hypoxia events. The report indicates that adaptation measures need to be a critical component of any long-term U.S. climate strategy. “The degree to which we can adapt to the consequences of climate change will be determined in large part by the policies and management practices we put in place today,” said Pew Center president Eileen Claussen. For more information, visit the Web site: http://www.pewclimate.org.
Effects of 2-Chloroethylphosphonic Acid and Gibberellic Acid on Sex Expression and Growth of Pumpkins

Treatment of pumpkin plants with 2-chloroethylphosphonic acid (CEPHA) induced a greater production of female flowers, shorter internodes and earlier fruit set while treatment with gibberellic acid (GA) induced a greater production of male flowers, longer internodes and later fruit set. Although CEPHA induced the production of a greater number of female flowers, the bulk of the flowers aborted and only a slight increase in the number of fruits per pumpkin plant occurred. The addition of equal concentrations of CEPHA and GA resulted in pumpkin plants with longer internodes and a greater number of female flowers than the untreated plants, although GA partially overcame the effect of CEPHA. The mode of action of CEPHA and GA on sex expression is discussed.
Goal Programming to Assist in Decision Making

Abstract Goal programming is a systematic method of decision making with potential for assisting fishery managers and administrators achieve a practical decision when there are multiple or conflicting goals. The technique involves formulating the decision problem by identifying and establishing goals, setting priorities for achieving the goals, and determining what constraints exist on the availabilities of monetary and nonmonetary resources. A model of the problem, formulated as a modification of the simplex method of linear programming, can be solved by hand or with a computer program. The resulting solution gives recommended levels of each choice variable that best achieve stated goals. We describe the construction of a model for goal programming with an example of a fish stocking problem, and perform a sensitivity analysis of goal priorities to demonstrate how the effects on the solution to the problem can be determined. Goal programming supplements, but does not replace, the judgment of good managers...
Steroid modulation of cytokine release and desmosine levels in bilateral total knee replacement: a prospective, double-blind, randomized controlled trial.

Background: The perioperative inflammatory response as measured by elevated levels of interleukin-6 (IL-6) has been linked to acute respiratory distress syndrome, postoperative confusion, and fever. Because of the extent of surgery, patients undergoing bilateral total knee arthroplasty may be at high risk of complications. We had found a significant decrease in IL-6 in patients having bilateral total knee replacement who received two doses of 100 mg of hydrocortisone eight hours apart; however, by twenty-four hours, IL-6 levels were equal to those in the group that received a placebo. In the present study, we investigated whether the administration of three doses would reduce IL-6 levels at twenty-four hours and affect other outcomes such as desmosine level, a marker of lung injury. Methods: After institutional review board approval, a total of thirty-four patients (seventeen patients and seventeen control subjects) were enrolled in this double-blind, randomized, placebo-controlled study. Three doses of intravenous hydrocortisone (100 mg) or placebo were given eight hours apart. Urinary desmosine levels were obtained at baseline and at one and three days postoperatively. The level of IL-6 was measured at baseline and at six, ten, twenty-four, and forty-eight hours postoperatively. Pain scores, presence of fever, and functional outcomes were recorded. Results: The level of IL-6 increased in both groups, but was significantly higher in the control group, peaking at twenty-four hours (mean and standard deviation, 623.74 ± 610.35 pg/mL versus 148.13 ± 119.35 pg/mL; p = 0.006). Urinary desmosine levels significantly increased by twenty-four hours in the control group, but remained unchanged in the study group (134.75 ± 67.88 pmol/mg and 79.45 ± 46.30 pmol/mg, respectively; p = 0.006). Pain scores at twenty-four hours were significantly lower in the study group (1.4 ± 0.9 versus 2.4 ± 1.2; p = 0.01) as was the presence of fever (11.8% versus 47.1%; p = 0.03). Range of motion at the knee was significantly greater in the study group (81.6 ± 11.6 versus 70.6 ± 14.0 in the right knee [p = 0.02] and 81.4 ± 11.3 versus 73.4 ± 9.4 in the left knee [p = 0.03]). Conclusions: Hydrocortisone (100 mg) given over three doses, each eight hours apart, decreased and maintained a lower degree of inflammation with bilateral total knee replacement as measured by IL-6 level. Corticosteroids decreased the prevalence of fever, lowered visual analog pain scores, and improved knee motion. The significantly lower values of desmosine in the study group suggest that this treatment may be protective against lung injury. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
Enzyme therapy. V. In vivo fate of erythrocyte-entrapped beta-glucuronidase in beta-glucuronidase-deficient mice.

Extract: The use of erythrocyte entrapment as a strategy to deliver and protect exogenously administered enzymes for replacement therapy in selected genetic diseases has been evaluated in a mammalian model system. The uptake, tissue distribution, intracellular localization, and in vivo lifetime of erythrocyte-entrapped bovine β-glucuronidase were determined by a selective thermal inactivation assay after intravenous administration into β-glucuronidase-deficient mice. The exogenous activity was cleared from the circulation with a half-life of about 20 min and was no longer detectable at 2 hr. A concomitant uptake of the injected enzyme was observed in murine tissues, primarily the liver; approximately 30% of the bovine activity was recovered at 30 min and maximal hepatic uptake, 71% of dose, was detected at 2 hr. Hepatic recovery of the bovine activity was observed to decrease in a biphasic pattern to nondetectable levels by 5 days. The recovery of the entrapped activity was characterized by a latency of detection in hepatic tissue up to 13 hr postinjection. At each time point more than 80% (84-100%) of the recovered bovine activity was detected in the lyso-somally enriched hepatic subcellular fraction. Maximal recoveries of 10 % and 15% of administered dose were observed in splenic and renal tissues, respectively, soon after enzyme administration. In comparison to results obtained after intravenous administration of unentrapped bovine β-glucuronidase, erythrocyte-entrapped activity was retained fourfold longer in the circulation, fivefold longer in hepatic tissue, and was more efficiently delivered to a variety of tissues. Speculation: Entrapment in autologous erythrocytes may provide an effective means to optimize the delivery and protection of exogenous enzymes for the treatment of selected lysosomal storage diseases, such as Fabry and type 1 Gaucher diseases, by enzyme replacement therapy. Furthermore, efficient delivery to specific target sites of pathology may be accomplished by the entrapment of other therapeutic agents within these biodegradable vesicles.
Progress in ab initio QM/MM free-energy simulations of electrostatic energies in proteins: accelerated QM/MM studies of pKa, redox reactions and solvation free energies.

Hybrid quantum mechanical / molecular mechanical (QM/MM) approaches have been used to provide a general scheme for chemical reactions in proteins. However, such approaches still present a major challenge to computational chemists, not only because of the need for very large computer time in order to evaluate the QM energy but also because of the need for proper computational sampling. This review focuses on the sampling issue in QM/MM evaluations of electrostatic energies in proteins. We chose this example since electrostatic energies play a major role in controlling the function of proteins and are key to the structure-function correlation of biological molecules. Thus, the correct treatment of electrostatics is essential for the accurate simulation of biological systems. Although we will be presenting here different types of QM/MM calculations of electrostatic energies (and related properties), our focus will be on pKa calculations. This reflects the fact that pKa of ionizable groups in proteins provide one of the most direct benchmarks for the accuracy of electrostatic models of macromolecules. While pKa calculations by semimacroscopic models have given reasonable results in many cases, existing attempts to perform pKa calculations using QM/MM-FEP have led to large discrepancies between calculated and experimental values. In this work, we accelerate our QM/MM calculations using an updated mean charge distribution and a classical reference potential. We examine both a surface residue (Asp3) of the bovine pancreatic trypsin inhibitor, as well as a residue buried in a hydrophobic pocket (Lys102) of the T4-lysozyme mutant. We demonstrate that by using this approach, we are able to reproduce the relevant sidechain pKas with an accuracy of 3 kcal/mol. This is well within the 7 kcal/mol energy difference observed in studies of enzymatic catalysis, and is thus sufficient accuracy to determine the main contributions to the catalytic energies of enzymes. We also provide an overall perspective of the potential of QM/MM calculations in general evaluations of electrostatic free energies, pointing out that our approach should provide a very powerful and accurate tool to predict the electrostatics of not only solution but also enzymatic reactions, as well as the solvation free energies of even larger systems, such as nucleic acid bases incorporated into DNA.
Effect of Primary Hypothyroidism on Fetal Mouse Lung Surfactant Protein A, B and C, and Thyroid Transcription Factor-1 Protein and Gene Expression.† 1456

Primary hypothyroidism in the Hyt/Hyt mice is due to a point mutation(Pro-556-Leu) in the β subunit of the TSH receptor of the thyroid gland and is transmitted as an autosomal recessive trait. Fetal hypothyroidism is associated with delayed fetal lung ultrastructural maturation (Ped. Res. 36:380:94). Surfactant proteins (SP-A, B & C) & Thyroid Transcription Factor-1 (TTF-1) play an important role in fetal lung surfactant function and type II cell differentiation, but the effect of primary hypothyroidism on the developmental expression of fetal lung SP-A, SP-B, SP-C or TTF-1 has not been investigated. Hyt/Hyt mice identified by high serum TSH and low free T4 levels were made euthyroid by supplemental T3. The mice were then bred to carry Hyt/Hyt pups. Balb-c euthyroid mice served as controls. All mice were killed on d 18 of gestation (term ≈20 d, vaginal plug = d 1 of pregnancy). Fetal lung immunostaining for SP-A, SP-B, SP-C and TTF-1 was performed and gene expression of these proteins was determined by Northern blot analysis. The TTF-1 immunoreactivity was nuclear in localization and confined to the type II cells, while staining for SP-A, SP-B and SP-C was cytoplasmic and present in type II cells as well as within the alveolar lumen. The intensity and distribution of the immunoreactivity scored on a scale of 0 to 3, for SP-A, SP-B and SP-C and TTF-1 (n=5) was markedly decreased in the Hyt/Hyt fetal lungs when compared to the controls (n=5). While gene expression for SP-C(≈0.8 kb) and TTF-1 (≈2.3 kb) was significantly decreased in the hyt/hyt mice, the gene expression for SP-B (≈0.9 kb) was similar in both groups. CON: Primary hypothyroidism is associated with a delay in the developmental expression of fetal lung SP-A, SP-B, SP-C and TTF-1 protein, and a differential expression for SP-B, SP-C and TTF-1 genes. These findings may explain a higher incidence of RDS in human neonates with hypothyroidism(NIH-HL 52839).
Transparent flow migration through splicing for multi-homed vehicular Internet gateways

We propose a technique, called FloMiS, by which a flow can be migrated from one network to another without requiring any changes to the endpoints (Internet-based servers or mobile clients). Our work is motivated by the needs of our vehicular Internet service, calledWiRover, through which we provide WiFi connectivity in public transit vehicles - city buses as well as long distance buses operating in and around Madison, WI - using multi-network gateways. In our vehicular environment, we have observed that each cellular path experiences stalls and failures resulting in outages to network traffic. To provide robust and uninterrupted experience for these flows, we implement the FloMiS mechanism in the gateways alone, through which the gateways re-initiate a request for the contents of the interrupted flow and splice them back to the original flow in a manner that is transparent to the mobile clients. FloMiS is designed to optimize the majority of network traffic, which our analysis (of about 6 million real user flows) indicates that FloMiS is capable migrating a flow in as little as two round trip times for more than 93% of the traffic volume. Clients left to their own mechanisms would typically recover after several minutes of disconnectivity.
CFD Conjugate Analysis of a Jet-Impingement Configuration With Sudden Changes in Heating and Cooling Loads

The temperature in a material could exceed the maximum allowable during transients when the heat load is suddenly increased despite a corresponding increase in cooling. This is because there is a time lag in the response of the material. Unsteady RANS based on the shear-stress transport model with conjugate analysis were used to study the unsteady heating and cooling of a superalloy flat plate with a thickness of 1 mm. The flat plate was initially at steady-state conditions, heated on one side by a constant heat flux of 10 W/cm2 and cooled on the other side by impingement of air jets such that the maximum temperature in the plate was just below 900 °C, where 900 °C was taken to be the maximum allowable material temperature. Suddenly, the heating load was increased from 10 W/cm2 to 68 W/cm2 with a corresponding increase in the cooling such that the maximum temperature in the plate remains just below 900 °C when steady state is reached. Results obtained show that though the maximum temperatures at the two steady states are just below 900 °C, the highest temperature in the material can exceed 900 °C by up to 14 seconds during the transient from one steady state to the other. Thus, the minimum cooling flow based on steady-state conditions are inadequate during the transient process if the sudden heating and cooling occurred simultaneously. However, if the increase in cooling preceded the sudden increase in heating by a sufficient amount of time (i.e., pre-cooling), then over temperature was found to not occur during the transient. This paper presents results that show the unsteady flow and heat transfer in the fluid phase and the transients in the solid phase with and without pre-cooling.© 2013 ASME
Dynamic Social Networks in Recovery Homes

Acute treatment aftercare in the form of sober living environments—i.e., recovery houses—provide an inexpensive and effective medium-term treatment alternative for many with substance use disorders. Limited evidence suggests that house-situated social relationships and associated social support are critical determinants of how successful these residential experiences are for their members, but little is known about the mechanisms underlying these relationships. This study explored the feasibility of using dynamic social network modeling to understand house-situated longitudinal associations among individual Alcoholics Anonymous related recovery behaviors, length of residence, dyadic interpersonal trust, and dyadic confidant relationship formation processes. Trust and confidant relationships were measured 3 months apart in U.S. urban-area recovery houses, all of which were part of a network of substance use recovery homes. A stochastic actor-based model was successfully estimated from this data set. Results suggest that confidant relationships are predicted by trust, while trust is affected by recovery behaviors and length of residence. Conceptualizing recovery houses as a set of independent, evolving social networks that can be modeled jointly appears to be a promising direction for research.
HgTe-CdTe Superlaltice and HgCdTe Epilayer Device Structures Grown by Photon-Assisted Molecular Beam Epitaxy

HgCdTe grown by photon-assisted molecular beam epitaxy is now suitable for use in high performance detector fabrication. These are the preliminary results for infrared detectors which have been fabricated in HgCdTe grown using this technique at GE. The detectors were fabricated using a modified Hg-diffused diode process. In addition, the first high quantum efficiency infrared detectors based on the HgTe-CdTe superlattice material system is presented as an example of the sophisticated structures obtainable with photon-assisted molecular beam epitaxy. The superlattice detectors exhibited quantum efficiencies as large as 66% (at 140K) at the peak wavelength of 4.9μ and an average quantum efficiency over the 3-5μ waveband of 55%.
Mucosal Immunity in the Genital Tract: Prospects for Vaccines Against Sexually Transmitted Diseases—A Review

PROBLEM: Consistent with the absence of protective immunity resulting from previous infection with Neisseria gonorrhoeae, the genital mucosal immune response in human gonorrhea is weak: only low levels of immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies are detectable against gonococci, and inflammatory cytokine responses are poor. METHOD OF STUDY: Mucosal immunization strategies designed to induce persisting genital antibody responses might afford protection against infection, if appropriate conserved antigens can also be identified. RESULTS: Intragastric or intranasal immunization with bacterial antigens expressed as recombinant chimeric proteins with cholera toxin A2/B subunits induced persisting IgA antibodies in genital and other secretions, and circulating IgG antibodies. CONCLUSION: Although gonococci may avoid inducing or even suppress immune responses during natural infection, alternative approaches to vaccine development may be successful. However, inadequate understanding of the origins of antibodies in the genital tract, and their effector mechanisms, will need to be rectified to make this possible.
Family members of individuals with alcohol or drug disorders: Health care and costs over 8 years

associated with stable recovery. We analyzed data from a longitudinal study of 581 heroin users admitted to the California Civil Addict Program during 1962–1964 and followed for 30years. Findings showed that before 1986– 1987, approximately 30% reportedmore than 5years of heroin abstinence and 25% reported more than 5years in recovery (defined as heroin abstinence and no incarceration). Longer periods of abstinence were associated with a higher likelihood of remaining abstinent over the subsequent 10-year period (r= .73). Individuals who accumulated five or more years of abstinence were less likely to use, less likely to be involved in criminal justice system, and had better emotional and social functioning. Understanding factors that promote stable recovery can inform health service system policy and design.