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Structural failures after rotator cuff repair are well known, and despite advances and improved techniques in rotator cuff repair (RCR), retear rates remain high. The aim of this study was to (1) evaluate the midterm clinical and radiological outcomes after revision RCR and to (2) analyze whether preoperative ultrasound can predict outcome of open revision rotator cuff repair. Twenty-five patients who underwent revision RCR in a single institution between 2010 and 2012 were retrospectively reviewed at a minimum follow-up of 2 years. The Constant Score (CS) and the Disabilities of the Arm, Shoulder and Hand score were collected. Ultrasound examination was used both before revision surgery and at follow-up to determine tendon integrity. At the final follow-up, 69.6% patients showed an intact rotator cuff and their CS had improved from 28.3 to 77. 30.4% patients had a persisting rotator cuff defect, and the CS had improved from 24 to 47.7. A preoperative tear size of more than 20 mm from an ultrasound examination could be identified as a factor that would risk structural failure of revision RCR. (1) Clinical outcomes after revision RCR improve in both patients with an intact RC and those with a retear at midterm follow-up. (2) Ultrasound seems to be a useful tool to predict whether reconstruction of recurrent rotator cuff tears is feasible. IV, Case series.

The need for hollow microneedle arrays is important for both drug delivery and wearable sensor applications; however, their fabrication poses many challenges. Hollow metal microneedle arrays residing on a flexible metal foil substrate were created by combining additive manufacturing, micromolding, and electroplating approaches in a process we refer to as electromolding. A solid microneedle with inward facing ledge was fabricated with a two photon polymerization (2PP) system utilizing laser direct write (LDW) and then molded with polydimethylsiloxane. These molds were then coated with a seed layer of Ti/Au and subsequently electroplated with pulsed deposition to create hollow microneedles. An inward facing ledge provided a physical blocking platform to restrict deposition of the metal seed layer for creation of the microneedle bore. Various ledge sizes were tested and showed that the resulting seed layer void could be controlled via the ledge length. Mechanical properties of the PDMS mold was adjusted via the precursor ratio to create a more ductile mold that eliminated tip damage to the microneedles upon removal from the molds. Master structures were capable of being molded numerous times and molds were able to be reused. SEM/EDX analysis showed that trace amounts of the PDMS mold were transferred to the metal microneedle upon removal. The microneedle substrate showed a degree of flexibility that withstood over 100 cycles of bending from side to side without damaging. Microneedles were tested for their fracture strength and were capable of puncturing porcine skin and injecting a dye.

Purpose: Expression-based classifiers to predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) are not routinely used in the clinic. We aimed to build and validate a classifier for pCR after NACT. Patients and Methods: We performed a prospective multicenter study (EXPRESSION) including 114 patients treated with anthracycline/taxane-based NACT. Pretreatment core needle biopsies from 91 patients were used for gene expression analysis and classifier construction, followed by validation in five external cohorts (n = 619). Results: A 20-gene classifier established in the EXPRESSION cohort using a Youden index–based cut-off point predicted pCR in the validation cohorts with an accuracy, AUC, negative predictive value (NPV), positive predictive value, sensitivity, and specificity of 0.811, 0.768, 0.829, 0.587, 0.216, and 0.962, respectively. Alternatively, aiming for a high NPV by defining the cut-off point for classification based on the complete responder with the lowest predicted probability of pCR in the EXPRESSION cohort led to an NPV of 0.960 upon external validation. With this extreme-low cut-off point, a recommendation to not treat with anthracycline/taxane-based NACT would be possible for 121 of 619 unselected patients (19.5%) and 112 of 322 patients with luminal breast cancer (34.8%). The analysis of the molecular subtypes showed that the identification of patients who do not achieve a pCR by the 20-gene classifier was particularly relevant in luminal breast cancer. Conclusions: The novel 20-gene classifier reliably identifies patients who do not achieve a pCR in about one third of luminal breast cancers in both the EXPRESSION and combined validation cohorts.

Areas impacted by petroleum refining and handling operations may become subject to CERCLA enforcement. Because of CERCLA's petroleum exclusion clause, determining whether contamination in a CERCLA Site originated from petroleum products or hazardous wastes becomes important. Because certain metals are typically enriched in wastes relative to petroleum products and background soils, knowledge of metal contents in these potential end member metal sources is an important step towards contaminant source identification in soils and sediments. In LNAPL plumes, metal content, particularly lead, may be claimed to be the result of wastes mishandling and not due only to the presence of leaded gasoline in the plume. Analysis of the percent gasoline in the plume and accounting for weathering are steps to determining whether the lead content in an LNAPL plume is within the historical lead concentration ranges in gasolines. In addition to metals analyses, understanding of operational parameters such as the hist...

Die Implantation einer anatomischen Schultertotalprothese fuhrt bei fortgeschrittenem Glenoidverbrauch zu einer hoheren Lockerungsrate der Glenoidkomponente und schlechteren funktionellen Ergebnissen. Ziel der Auswertung der Daten des Deutschen Schulterendoprothesenregisters war zu klaren, ob die Implantation einer inversen Schulterprothese bei fortgeschrittenem bikonkavem Glenoidverbrauch Typ B2 nach Walch im Vergleich zur anatomischen Schulterprothese Vorteile aufweist. 1052 vollstandig dokumentierte primar implantierte Prothesen konnten nach Datenbereinigung mit einem Mindestnachuntersuchungszeitraum von 2 Jahren in die Auswertung eingeschlossen werden. 119 Patienten wiesen ein B2-Glenoid auf. Bei 86 Patienten wurde eine anatomische und bei 33 Patienten eine inverse Prothese implantiert. Der durchschnittliche Nachuntersuchungszeitraum betrug 47,6 Monate. Nach anatomischer als auch nach inverser Prothesenimplantation verbesserte sich der Constant Score mit seinen Subkategorien und auch das aktive Bewegungsausmas signifikant durch die Prothesenimplantation. Im funktionellen Ergebnis zeigten sich bisher keine Unterschiede zwischen beiden Implantattypen, wohingegen Revisionseingriffe signifikant haufiger nach inverser Prothese (21,2 %) (haufigste Indikationen: 3 % Glenospharenlockerung, 6 % Protheseninstabilitat) als nach anatomischer Prothese (12,8 %) (11,6 % Glenoidlockerung, 1,2 % Protheseninstabilitat) erfolgten, obwohl anatomische Prothesen eine hohere Rate an Glenoidlockerungen aufwiesen. Die funktionellen als auch radiologischen Ergebnisse sind fur beide Prothesentypen mit der Literatur vergleichbar, obwohl es sich um Registerdaten (Daten der Versorgungsqualitat) handelt.

Traditionally, the representativeness and sufficiency of data in environmental monitoring efforts are judged against an external standard, such as a pre-determined statistically-based survey design intended to achieve specified data quality objectives. However, given the nature of oil spill responses, where the primary focus is usually on finding the oil and documenting exposure related to the release, samples collected from oil spill studies rarely follow a statistically-based, pre-determined sampling design. Using water chemistry data from the Deepwater Horizon oil spill, we have developed statistical, observational, and forensic approaches to evaluate the representativeness and sufficiency of field-collected chemistry data to characterize exposure in the water column. Three complementary approaches were selected for evaluating water chemistry data. The first “Zone” approach evaluates properties of the data within defined spatial-temporal exposure zones. The second “Probability” approach examines the data independent of predetermined zones using three dimensional (3D; i.e., latitude, longitude, depth) modeling methods (interpolation, contouring) to assess whether the field-collected water chemistry data alone provide sufficient information to model chemical exposure in the water column. The final “Design” approach compares the field-collected sample data to a theoretical sampling design that could have been developed at the beginning of the incident. Integral to all of these approaches is a pre-analysis screening that considers the original objective of each sample collection and the method of sample collection. Review of the chemical forensics of samples can provide further refinement. In this way, samples that were collected as part of a targeted effort based on visual or sensor observations can be considered in light of the context in which they were collected. The results of this analysis can be used to inform future oil spill sample collections to provide sufficient and representative samples that meet the immediate needs of the response as well as longer-term damage assessment determinations.

2017-284:Over the past decade, three realizations have evolved from our collection and analysis of oil spill data. First is that more response data are being collected than ever before, including field and laboratory measurements in addition to observational data. To process this diverse information, we use sophisticated computer-based systems that allow us to integrate, analyze, and visualize satellite imagery, real-time weather and ship locations, field notes (e.g., shoreline cleanup assessment technique [SCAT] data), chemistry data, and photos. The second is the increased political and social interest in spills. Increased use of social media and the impact of these information pathways on the public’s perception of the spill response can drive real political decisions; making spill communications based on timely and high data quality critical. Lastly is the growing linkages between the collection, management, and uses of environmental data, not only for spill response, but also for NRD assessment (NRDA), determination of civil penalties (e.g., the Clean Water Act [CWA]), and third party legal claims. For example, observational and remote sensing data collected for response actions will ultimately be used to understand questions about contaminant pathways and exposures inherent to NRDA. Similarly, data collected as part of response mitigation and cleanup needs often provides our earliest understanding of the potential and actual natural resource damage issues, which are important for NRDA, third party claims, and CWA penalty mitigation.Historically, the inherent differences in temporal and spatial scales over which oil spill data are collected and used, coupled with the requirements of data quality, usability, and/or provenance, diminishes the ability to effectively optimize collection and uses of these data. Data optimization recognizes that data can/will have multiple uses and thus requires all data, whether response or NRDA-related to be of high and equivalent quality and be based on compatible, if not identical, data quality objectives (DQOs). In this paper, we review several examples that underscore the need for data optimization in environmental data collection. Specifically, we will explore how a focus on the long view and the need for data optimization can drive the collection of appropriate and multipurpose data, as well as inform the structure of data management systems. Using specific examples, we will demonstrate the value of embracing a data optimization framework in developing a common sample/data collection imperative that facilitates multiple uses.

2017-192 While examination of the question “what happened to the oil?” has been undertaken on other oil spills, the wealth of data from the 2010 Deepwater Horizon accident presents a unique opportunity to deeply examine this question. To do so, several investigative threads need to be pulled together. In this paper, results from several relevant data sets and related studies and published papers pertaining to the behavior and fate of oil released from the Macondo well during the accident will be discussed. These data sets include: 1) analysis of the weathering processes, changes in chemistry, and partitioning of oil components that occurred and 2) data on the concentrations and movement of oil in the water, on the surface, and to the shoreline that created various “footprints” over time. The available data on water column chemistry, distributions, and partitioning; water chemistry related to surface oil distributions over time; biodegradation; sediment chemistry and distributions; and fate of the oil on the shoreline are all essential to this effort. This presentation will present a high-level, data-driven overview of the fate of the oil.

Assessing the environmental impact of spilled oil and gas requires an understanding of both the petroleum’s movement and the physical and chemical changes it undergoes after the release. Deep subsea releases differ from surface releases primarily because of the extended interaction of the oil and gas with the water column prior to atmospheric exposure. Furthermore, the remote locations and uncertain volumes of deep subsea oil and gas releases result in logistical challenges to data collection both during and after a release. However, there have been multiple subsea releases with large-scale environmental investigations, and the extensive investigation undertaken during and after the Deepwater Horizon (DWH) spill resulted in an especially comprehensive empirical data set. The specific chemical and physical properties of the oil and gas mixtures in subsea releases differ between spills, and the DWH investigation and others have highlighted the importance of understanding biodegradation rates and transport to offshore sediments. The field and experimental data collected during and after a spill can improve oil fate prediction when incorporated into comprehensive oil spill models.

While censored data (i.e., containing non-detect [ND] results) may provide useful information in the context of risk assessment, their utility in chemical forensics is less clear. Substitution of NDs can create invasive patterns and may obscure the true forensic features in the underlying chemistry and sample compositions. The effect of substituting numeric values for NDs on the results of common chemical forensics multivariate analyses is illustrated using synthetic simulated data and laboratory measurements of soil samples from Colorado. The analyses of simulated and laboratory data demonstrate the impact of substituting values for NDs on multivariate analyses and indicate the potential for incorrect conclusions about the true forensic features within the data. Recommendations are provided for how to investigate and visualize the impact of NDs on chemical forensic multivariate analyses.

Tamoxifen, a selective estrogen receptor modulator, is widely used in mouse models to temporally control gene expression but is also known to affect body composition. Here, we report that tamoxifen has significant and sustained effects on glucose tolerance, independent of effects on insulin sensitivity, in mice. Intraperitoneal, but not oral, tamoxifen delivery improved glucose tolerance in three inbred mouse strains. The extent and persistence of tamoxifen-induced effects were sex- and strain-dependent. These findings highlight the need to revise commonly used tamoxifen-based protocols for gene manipulation in mice by including longer chase periods following injection, oral delivery, and the use of tamoxifen-treated littermate controls.

Background Novel therapies are replacing established treatment options for patients with advanced non-small cell lung cancer (aNSCLC), which poses a challenge to healthcare budgets. The impact of Treatment Evolution in NSCLC (iTEN) model is a validated discrete event patient simulation designed to estimate the impact of treatment sequencing in aNSCLC. The impact of five novel therapies (osimertinib, alectinib, brigatinib, dabrafenib and trametinib, and pembrolizumab combination therapy) changing aNSCLC management in Canada was modelled. Methods Current Canadian treatment practices were established via a modified Delphi process with Canadian clinical experts. The table presents potential treatment sequences for biomarker positive aNSCLC with the novel therapies. Clinical efficacy of treatments was estimated from Kaplan–Meier progression-free and overall survival data, as previously described (Moldaver et al. 2018). Modelled costs (2018 CDN $) included drug acquisition and administration costs and the costs of ongoing monitoring, imaging, physician visits, end-of-life, best supportive care, and adverse event management. A treatment rate of 100% in the first-line and 60% thereafter was modelled. Table . 1582P Biomarker positive aNSCLC therapy EGFR ALK BRAF PD-L1 ≥ 50% PD-L1 1L Osimertinib* Alectinib* Dabrafenib plus trametinib* Pembrolizumab Pembrolizumab plus chemotherapy* 2L PD Brigatinib* IO for those PD-L1 ≥ 50% PD for remainder PD Docetaxel 3L I-O PD Switch (PD to I-O and I-O to PD) Docetaxel Erlotinib 4L Docetaxel/BSC I-O Docetaxel Erlotinib/BSC BSC Therapies with an asterisk (*) are new to Canada BSC, best supportive care; I-O, immuno-oncology agent; PD, platinum doublet chemotherapy Results Introduction of these five therapies was estimated to increase the average 1- and 3-year survival of Canadian aNSCLC patients from 69% and 14% to 73% and 21%, respectively. Estimated average lifetime cost per treated patient rose from $159,764 to $269,056. ALK positive patients were estimated to have the largest increase in 3-year survival, from 35% to 64%, and cost of treatment, from $315,333 to $747,859. Conclusions New therapies for aNSCLC are likely to increase the survival and average cost of treatment in Canada. Legal entity responsible for the study The authors. Funding AstraZeneca Canada. Disclosure P.K. Cheema: Honoraria (self), Advisory / Consultancy: AstraZeneca Canada, BI, BMS, Roche, Pfizer, Novartis, Takeda and Merck,. W.K. Evans: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca Canada, AbbVie, Astellas, BMS, Eisai, Lilly, Janssen, Gilead, Takeda, Boehringer Ingelheim, Roche and Celgene. R. Burkes: Honoraria (self), Advisory / Consultancy: AstraZeneca Canada. R. Sangha: Honoraria (self), Advisory / Consultancy: Pfizer, BI, AZ, Roche/Genentech, Lundbeck, BMS, Merck, AbbVie and Takeda, Lilly, BMS, Novartis. C. Ho: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca Canada, Boehringer Ingelheim, Pfizer, BMS, Roche, Lilly, Genzyme, Eisai, Merck and Bayer. P. Wheatley-Price: Honoraria (self), Advisory / Consultancy, Leadership role: Novartis, BMS, Merck, AZ, Takeda, Roche and AbbVie. D. Boehm: Honoraria (self): AstraZeneca Canada, Baxter and Genomic Health. J. Venkatesh: Honoraria (self): AstraZeneca Canada, Takeda. S. Walisser: Honoraria (self), Advisory / Consultancy: stellas Pharma Canada, AstraZeneca Canada, Gilead Sciences Canada, Pfizer, and Janssen Inc. D. Grima: Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Cornerstone Research Group. D. Moldaver: Full / Part-time employment: Cornerstone Research Group. M. Hurry: Full / Part-time employment: AstraZeneca Canada.

Background Occupational hand eczema (OHE) is associated with impaired health-related quality of life (QoL) and mental distress. Interdisciplinary inpatient rehabilitation measures in the framework of tertiary individual prevention (TIP) offered by the German employers' liability insurance associations include dermatological treatment, education and psychological interventions. Objective To investigate the effects of interdisciplinary inpatient rehabilitation in the framework of TIP on mental health in patients with severe OHE and the relationships between recovery of OHE and improvement of mental health and QoL. Methods A total of 122 patients participated in the study. A test battery consisting of the German versions of the Hospital Anxiety and Depression Scale (HADS-D), the Dermatology Life Quality Index (DLQI), the Short Form Health Survey-36 (SF-36) and the Trier Inventory for the Assessment of Chronic Stress (TICS) was applied at the time of admission (T1) and 3 weeks after dismissal (T2). Severity of hand eczema was assessed with the Osnabrueck Hand Eczema Severity Index (OHSI). Results All parameters improved significantly from T1 to T2. A relationship was established between the improvement of QoL and recovery of OHE, while there was no such relationship between the improvement of mental distress and improvement of OHE. Nonresponders had significantly more cumulative days of sickness at T1. Conclusions Our data underscore the importance of psychological interventions in addition to dermatological treatment in the framework of prevention measures for OHE. These measures should be applied at an early stage of OHE prior to the occurrence of sick leave.

A realistic understanding of contaminant sources is required to set appropriate control policy. Forensic chemical methods can be powerful tools in source characterization and identification, but they require a multiple-lines-of-evidence approach. Atmospheric receptor models, such as the US Environmental Protection Agency (USEPA)'s chemical mass balance (CMB), are increasingly being used to evaluate sources of pyrogenic polycyclic aromatic hydrocarbons (PAHs) in sediments. This paper describes the assumptions underlying receptor models and discusses challenges in complying with these assumptions in practice. Given the variability within, and the similarity among, pyrogenic PAH source types, model outputs are sensitive to specific inputs, and parsing among some source types may not be possible. Although still useful for identifying potential sources, the technical specialist applying these methods must describe both the results and their inherent uncertainties in a way that is understandable to nontechnical policy makers. The authors present an example case study concerning an investigation of a class of parking-lot sealers as a significant source of PAHs in urban sediment. Principal component analysis is used to evaluate published CMB model inputs and outputs. Targeted analyses of 2 areas where bans have been implemented are included. The results do not support the claim that parking-lot sealers are a significant source of PAHs in urban sediments. Integr Environ Assess Manag 2014;10:279–285. © 2013 SETAC

The process for conducting natural resource damage assessments (NRDAs) is supported by important scientific investigation components. The degree to which science forms the basis of NRD settlements varies by case, but all NRDAs depend to varying extents on scientific studies. While some of these investigation components have been discussed in previous papers and agency guidance, many of the scientific components remain anecdotal and poorly supported. This article presents each of several scientific components as an integrated investigation approach and gives recommendations and examples of the methodological features.

To interpret whole exome/genome sequence data for clinical and research purposes, comprehensive phenotypic information, knowledge of pedigree structure, and results of previous clinical testing are essential. With these requirements in mind and to meet the needs of the Centers for Mendelian Genomics project, we have developed PhenoDB (http://phenodb.net), a secure, Web-based portal for entry, storage, and analysis of phenotypic and other clinical information. The phenotypic features are organized hierarchically according to the major headings and subheadings of the Online Mendelian Inheritance in Man (OMIM®) clinical synopses, with further subdivisions according to structure and function. Every string allows for a free-text entry. All of the approximately 2,900 features use the preferred term from Elements of Morphology and are fully searchable and mapped to the Human Phenotype Ontology and Elements of Morphology. The PhenoDB allows for ascertainment of relevant information from a case in a family or cohort, which is then searchable by family, OMIM number, phenotypic feature, mode of inheritance, genes screened, and so on. The database can also be used to format phenotypic data for submission to dbGaP for appropriately consented individuals. PhenoDB was built using Django, an open source Web development tool, and is freely available through the Johns Hopkins McKusick-Nathans Institute of Genetic Medicine (http://phenodb.net).

615 Background: The chemokine CXCL13 is chemotactic for B cells. We examined the prognostic significance of CXCL13 mRNA expression in node-negative breast cancer. Methods: Microarray based gene-expression data for CXCL13 (205242_at) were analysed in four previously published cohorts (Mainz, Rotterdam, Transbig, Yu) of node-negative breast cancer patients not treated with adjuvant therapy (n=824). A meta-analysis of previously published cohorts was performed using a random effects model. Prognostic significance of CXCL13 on metastasis-free survival (MFS) was examined in the whole cohort and in different molecular subtypes (ER+/HER2-, ER-/HER2-, HER2+). Independent prognostic relevance was analysed using multivariate Cox regression. Results: Higher RNA expression of CXCL13 was related to better MFS in a meta-analysis of the whole cohort (HR 0.88, 95% CI 0.83-0.94, P

We designed and developed a high-speed atomic force microscope (HSAFM) utilizing a force-feedback scheme for imaging large biological samples. The system collects three simultaneous images: a deflection image, a topographic image, and a force image. We demonstrated that this force-feedback HSAFM is capable of acquiring large topographic images of Escherichia coli biofilms at approximately one frame per second in air. We discuss how the self-actuating cantilever and the piezo tube follow those larger biological topographic features during the HSAFM imaging process.

Background: The prognostic significance of CD8 positive cytotoxic lymphocytes in breast cancer is well accepted. However, the role of CD4 positive lymphocytes is ambiguous. We examined the prognostic relevance of CD4 positive tumor-infiltrating lymphocytes in previously published node-negative breast cancer cohorts using RNA expression. Methods: Microarray based gene-expression data for CD4 (203547_at) were analyzed in four previously published cohorts (Mainz, Rotterdam, Transbig, Yu) of node-negative breast cancer patients not treated with adjuvant therapy (n = 824). A meta-analysis of previously published cohorts was performed using a random effects model. Prognostic significance of CD4 on metastasis-free survival (MFS) was examined in the whole cohort and in different molecular subtypes (ER+/HER2−, ER−/HER2−, HER2+). Independent prognostic relevance was analyzed using multivariate Cox regression. Results: Higher RNA expression of CD4 was related to better MFS in a meta-analysis of the whole cohort (HR 0.66, 95% CI 0.49–0.90, p = 0.0074). Prognostic significance was most pronounced in the HER2+ positive molecular subtype (HR 0.32, 95% CI 0.14–0.75, p = 0.0091) as compared to ER+/HER2− (HR 0.62, 95% CI 0.29–1.32, P>0.05) and ER−/HER2− (HR 0.61, 95% CI 0.28–1.35, P>0.05) carcinomas of the breast. CD4 showed independent prognostic significance (HR 0.60, 95% CI 0.37–0.96, p = 0.032) in multivariate analysis. In addition to CD4, only histological grade of differentiation (HR 2.43, 95% CI 1.50–3.94, P < 0.001) and tumor size (HR 1.87, 95% CI 1.19–2.94, p = 0.007), but not age, HER2 status or hormone receptor status retained an independent prognostic association with MFS. Conclusion: CD4 positive tumor-infiltrating lymphocytes have independent prognostic significance in node-negative breast cancer. A higher expression is associated with improved outcome. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-13.

Um den komplexen Anspruchen an eine interdisziplinare Therapie von Herz-Kreislauferkrankungen gerecht zu werden, sind besondere strukturelle Voraussetzungen notwendig. Am vor sieben Jahren gegrundeten Universitaren Herzzentrum Hamburg sind alle kardiovaskularen Kliniken unter einem Dach zusammengefasst und auch ein Grosteil der Ressourcen wird gemeinsam genutzt. Ein enger interdisziplinarer Austausch sowie die patientenorientierte Behandlung im Heart Team werden dabei auch durch das gemeinsame Budget entscheidend vereinfacht. Anpassungen im internen Weiterbildungscurriculum tragen den gestiegenen Anforderungen an kunftige Herzchirurgen zusatzlich Rechnung.

Producers adjacent to a natural-gas storage field claimed that the natural gas they were producing was native gas from the area and not storage gas being pulled from the nearby gas storage field. The objective of this work is to apply a combination of area-specific and generic geochemical fingerprinting techniques to determine the source(s) of the natural gas being produced by third-party producers outside the gas storage field and to determine the extent of storage gas migration beyond geologic faults that lie between the production area and the gas storage field. An extensive set of natural-gas samples from the storage field, observation wells around the field, and third-party wells was analyzed for gas hydrocarbon and nonhydrocarbon compositions, as well as stable carbon isotopic compositions of methane and ethane. Gas chemical compositional data, including concentrations of the natural native gas tracer, helium, and ethane carbon isotope, were used to establish the unique fingerprints of native gas and storage gases (end-member sources) and to compare those end-member-source fingerprints to those of natural gas in the third-party wells. The analysis determined that gas in both the observation wells and third-party wells was, in fact, storage gas.

The ability to predict the timing and magnitude of future climate and temperature changes at a regional level has become increasingly important for corporate decision making and enterprise risk management. In the short term, companies could face decisions about acquisitions of water-dependent companies and natural resources or might be planning facilities or operations in communities vulnerable to erosion and flooding, changes in water supplies, and increasing health-care costs. In the intermediate term, companies need to assess these vulnerabilities to determine appropriate insurance coverage, plan for new infrastructure, implement preventative health-care programs, or protect natural resources. A technical approach needs to involve predictive tools that can provide bounding estimates at regional scales. The implications of those changes need to be translated to consequences that can affect specific businesses. Corporations must be cognizant of the uncertainties in this forecasting process and for that r...

Background: Aurora kinase A (AURKA) is important for cell cycle progression. Inhibitors that target AURKA are currently in clinical development. We examined the prognostic impact of AURKA in three cohorts of node-negative breast cancer patients without adjuvant systemic therapy (n=766). Methods: AURKA (probe set ID 204092_s_at) was analysed utilizing microarray based gene-expression data of three independent and previously published cohorts of node-negative breast cancer patients (Mainz, Rotterdam, TRANSBIG). In addition to AURKA, we examined the prognostic impact of age, histological grade, tumor size, estrogen receptor (ER) and HER2. Metastasis-free survival (MFS) was analyzed with univariate and multivariate Cox regression. Results: AURKA displayed a strong positive correlation with grade (P Conclusion: AURKA has prognostic relevance in three independent cohorts of node-negative breast cancer patients making it a suitable target for therapy with Aurora kinase inhibitors. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-22.

Background Ki-67 is a marker of proliferating cells; in this meta-analysis we aimed to examine whether Ki-67 expression can predict recurrence rates of breast ductal carcinoma in situ (DCIS). Materials and Methods This systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible articles were sought in MEDLINE up to April 30, 2017. Random effects (DerSimonian–Laird) models were used for the calculation of pooled relative risk (RR) estimates; meta-regression analysis was also performed. Separate analyses were performed according to Ki-67 expression cutoff levels, invasiveness of recurrence, and adjustment of studies. Results Ten eligible cohort studies were synthesized; a significant association between Ki-67 expression and DCIS recurrence was noted for the Ki-67 cutoff at 10% (RR = 1.66; 95% confidence interval [CI], 1.14-2.42) as well as the Ki-67 cutoff at 14% (RR = 1.67; 95% CI, 1.01-2.77). Subanalysis on unadjusted (RR = 1.48; 95% CI, 1.06-2.07) and adjusted studies (RR = 2.19; 95% CI, 1.42-3.38) replicated the statistically significant findings. Ki-67 expression predicted the risk of invasive (RR = 1.53; 95% CI, 1.14-2.06) and noninvasive (RR = 1.59; 95% CI, 1.19-2.13) recurrence. Conclusion This meta-analysis highlights Ki-67 expression as a predictor of DCIS recurrence; nevertheless, additional adjusted studies, with adequate follow-up periods, stemming from various world regions seem to be needed on this topic.

Purpose: Epithelial cell adhesion molecule (Ep-CAM) recently received increased attention not only as a prognostic factor in breast cancer but also as a potential target for immunotherapy. We examined Ep-CAM expression in 402 consecutive node-negative breast cancer patients with long-term follow-up not treated in the adjuvant setting. Experimental Design: Ep-CAM expression was evaluated by immunostaining. Its prognostic effect was estimated relative to overexpression/amplification of HER-2, histologic grade, tumor size, age, and hormone receptor expression. Results: Ep-CAM status was positive in 106 (26.4%) patients. In multivariate analysis, Ep-CAM status was associated with disease-free survival independent of age, pT stage, histologic grade, estrogen receptor (ER), progesterone receptor (PR), as well as HER2 status (P = 0.028; hazard ratio, 1.60; 95% confidence interval, 1.05-2.44). Recently, so-called triple-negative (HER-2, ER, and PR) breast cancer has received increased attention. We noticed a similar association of Ep-CAM with disease-free survival in the triple-negative group as for the entire cohort. Conclusion: In this study of untreated breast cancer patients, Ep-CAM overexpression was associated with poor survival in the entire cohort and in the subgroup of triple-negative breast cancer. This suggests that Ep-CAM may be a well-suited target for specific therapies particularly in HER-2–, ER-, and PR-negative tumors.

Identifying the causative variant from among the thousands identified by whole-exome sequencing or whole-genome sequencing is a formidable challenge. To make this process as efficient and flexible as possible, we have developed a Variant Analysis Module coupled to our previously described Web-based phenotype intake tool, PhenoDB (http://researchphenodb.net and http://phenodb.org). When a small number of candidate-causative variants have been identified in a study of a particular patient or family, a second, more difficult challenge becomes proof of causality for any given variant. One approach to this problem is to find other cases with a similar phenotype and mutations in the same candidate gene. Alternatively, it may be possible to develop biological evidence for causality, an approach that is assisted by making connections to basic scientists studying the gene of interest, often in the setting of a model organism. Both of these strategies benefit from an open access, online site where individual clinicians and investigators could post genes of interest. To this end, we developed GeneMatcher (http://genematcher.org), a freely accessible Website that enables connections between clinicians and researchers across the world who share an interest in the same gene(s).

Objective. Aggressive chemotherapy and radiotherapy or radical oncological surgery in young women with cancer has greatly enhanced these patients' life expectancy, but these treatments often cause infertility or premature ovarian failure due to a massive destruction of the ovarian reserve. The objective of this review is to discuss the effect of the various cancer treatments on fertility and present the various fertility sparing operations and fertility preservation strategies. Method. An extensive survey of the most up-to-date literature was performed. Results. This review discusses the impact of current cancer treatment on fertility potential and the various surgical and assisted-reproduction innovations available today for the most common cancers in young women. Although the ability to retain reproductive potential is becoming a major quality-of-life factor in an increasing number of young female cancer survivors, they are still being poorly counseled with regard to the negative impact of the treatment on their fertility and on their options for fertility preservation. Conclusion. As the emerging discipline of fertility preservation is steadily attracting increasing interest, developments in the near future promise to be very exciting. However, in everyday routine work, better interdisciplinary cooperation between gynecological and pediatric oncologists, surgeons, immunologists, and endocrinologists is necessary so that individualized options for fertility preservation can be offered in advance of surgical procedures or cancer treatments.

There has been much controversy regarding the origins of the natural polycyclic aromatic hydrocarbon (PAH) and chemical biomarker background in Prince William Sound (PWS), Alaska, site of the 1989 Exxon Valdez oil spill. Different authors have attributed the sources to various proportions of coal, natural seep oil, shales, and stream sediments. The different probable bioavailabilities of hydrocarbons from these various sources can affect environmental damage assessments from the spill. This study compares two different approaches to source apportionment with the same data (136 PAHs and biomarkers) and investigate whether increasing the number of coal source samples from one to six increases coal attributions. The constrained least-squares (CLS) source allocation method that fits concentrations meets geologic and chemical constraints better than partial least-squares (PLS) which predicts variance. The field data set was expanded to include coal samples reported by others, and CLS fits confirm earlier findings of low coal contributions to PWS.

Die zunehmende Inzidenz von Rotatorenmanschettendefekten (RMD) mit steigendem Alter stellt den Schulterchirurgen immer haufiger vor die Entscheidung, ob denn auch beim alteren Patienten eine Rekonstruktion sinnvoll und zu empfehlen ist. Anhand einer retrospektiven Analyse soll die Frage geklart werden, inwieweit sich die klinischen Ergebnisse nach offener Rekonstruktion eines RMD, die Defektgrose, Begleitpathologien und Redefektrate bei Patienten ab dem sechzigsten Lebensjahr von denen jungerer Patienten unterscheiden. Bei 76 Patienten mit einem Durchschnittsalter von 65 Jahren (60–78 Jahre) und bei 166 Patienten unter 60 Jahren wurde eine Rekonstruktion eines Rotatorenmanschettendefektes durchgefuhrt. Es erfolgte eine genaue Analyse aller intraoperativ erhobenen Befunde hinsichtlich der Rupturgrose, Affektionen des Acromioclavicular-Gelenks (ACG) und der langen Bizepssehne (LBS). Nach einem Follow-up von mindestens 2 Jahren wurde der Constant-Score erhoben sowie eine klinische und sonographische Nachuntersuchung durchgefuhrt. Die beiden Gruppen unterschieden sich hinsichtlich der intraoperativ gefundenen Rupturgrose (p=0,591) und der Haufigkeit kompletter LBS-Rupturen (p=0,61) sowie der Haufigkeit der sonographisch gefundenen Redefekte (p=0,341) nicht signifikant. Jedoch hatten die Patienten ab 60 Jahren mit einem durchschnittlichen alters- und geschlechtskorrigierten Constant-Score von 90% (13–126%) signifikant bessere Werte (p=0,002) als die Gruppe unter 60 Jahren mit 81,1% (15–116%). Bei den Patienten ab 60 fanden sich signifikant haufiger therapierelevante Affektionen des ACG (p

Good software cost models can significantly help software project managers. With good models, project stakeholders can make informed decisions about how to manage resources, how to control and plan the project, or how to deliver the project on time, on schedule, and on budget. Real-world data sets, such as those coming from software engineering projects, often contain noisy, irrelevant, or redundant variables. We propose that cost modelers should perform data-pruning experiments after data collection and before model building. Such pruning experiments are simple and fast.

Objective To evaluate topical interferon alfa 2b (IFNα2b) as a single therapeutic agent in the treatment of presumed recurrent corneal and conjunctival intraepithelial neoplasia. Design Noncomparative, retrospective case series. Participants Seven consecutive patients with recurrent corneal and conjunctival intraepithelial neoplasia diagnosed at the University of Minnesota from July 2000 to November 2003 were studied retrospectively. All patients had a history of histologically proven primary corneal and conjunctival intraepithelial neoplasia and were treated by surgery, cryotherapy, radiation, and/or topical mitomycin C before recurrence. Intervention Patients with a clinical diagnosis of recurrent corneal and conjunctival intraepithelial neoplasia were treated with recombinant topical IFNα2b drops (1 million IU/ml) 4 times daily until lesion resolution was noted. Main outcome measures A review of medical records was performed to assess the duration of and response to treatment with topical IFNα2b, defined by clinical resolution of corneal and conjunctival intraepithelial neoplasia. Results The average age of the 7 patients at the initiation of topical IFNα2b treatment for presumed recurrent corneal and conjunctival intraepithelial neoplasia was 68.7 years (range, 54–88). Six of 7 patients had successful treatment of recurrent corneal and conjunctival intraepithelial neoplasia lesions with topical IFNα2b treatment. The average length of IFNα2b treatment to resolution of recurrent corneal and conjunctival intraepithelial neoplasia was 14.5 weeks (range, 5–24). After treatment with topical IFNα2b for recurrent corneal and conjunctival intraepithelial neoplasia, 2 patients had another recurrence of corneal and conjunctival intraepithelial neoplasia, noted at 1 year and 2 months, respectively. The average post-treatment follow-up was 11.7 months (range, 8–17) after the resolution of recurrent corneal and conjunctival intraepithelial neoplasia. No side effects of treatment were noted in any patient. Conclusions Topical IFNα2b as a single therapeutic agent is an effective treatment of presumed recurrent corneal and conjunctival intraepithelial neoplasia. It offers the benefits of topical therapy and avoids the risks of surgical or other interventions—specifically, ocular surface toxicity, cicatricial conjunctival changes, and limbal stem cell deficiency. Larger controlled studies with longer follow-up periods are recommended to confirm the long-term efficacy and safety of this topical treatment.

Purpose: HER-2 blocking strategies, for instance with trastuzumab (Herceptin®), have been successfully used in therapy of breast cancer. To study molecular mechanisms and the efficiency of HER-2 blocking therapies we established a mouse tumor model that allows switching-off of HER-2 expression in tumor tissue. Material and Methods: NIH3T3 cells conditionally expressing HER-2 by the TET-OFF system (NIH3T3-HER-2 cells) were subcutaneously injected into the dorsal skin of nude mice. These cells allowed switching-off of HER-2 expression by exposure to anhydrotetracycline. We examined the influence of HER-2 down-regulation on tumor volume of subcutaneously growing tumors in nude mice. Tumor development was studied by magnetic resonance imaging. HER-2 expression was quantified by Western Blot analysis. Results: Eight to ten days after injection of 7 × 10 6 NIH3T3-HER-2 cells small subcutaneously growing tumors became visible. A surprisingly efficient tumor remission was observed already 7 days after switching-off of HER-2 expression: mice with initial tumor volumes of 0.8, 1.2, 3.9 and 14.9 cm 3 showed a decrease in tumor volumes to 1.9, 11.8, 11.3 and 25.8%, respectively, compared to the respective volumes before anhydrotetracycline administration. In contrast, a steady increase in tumor volume was observed for mice not exposed to anhydrotetracyclin. Conclusion: Switching-off of HER-2 expression causes a strong remission already after 7 days. Interestingly, the extent of tumor remission depends on initial tumor size, whereby a stronger remission can be achieved for smaller tumors. Our data support clinical studies testing HER-2 blocking strategies as adjuvant therapy for early breast cancer.

To evaluate the sources, transport, bioremediation, fate, and effects of spilled petroleum and petroleum products, environmental studies often measure parent and alkylated polycyclic aromatic hydrocarbons (PAH), alkanes, and chemical biomarkers (e.g., triterpanes). Accurate data for low analyte concentrations are required when environmental samples contain hydrocarbons from multiple sources that need to be resolved and quantified. The accuracy and usefulness of the analyses can be improved by lowering the method detection limits (MDLs) for these compounds. Misidentification of hydrocarbon source can result when the MDLs are too high. Modifications to standard analytical methods (i.e., U.S. Environmental Protection Agency Method 8270) can lower MDLs by factors ranging from 10 to 1000. This reduction has important implications for ecological-risk assessments. Modifications having the greatest impact on the MDL include GCMS analysis in the selected-ion-monitoring mode (SIM), increased sample size, column cleanup of the extract, and decreased preinjection volume (volume of final extract prior to injection into instrument). In one study in which a benthic sediment sample was spiked with low levels of topped (heated to remove more volatile PAH that are naturally enriched in crude oil) Alaska North Slope crude, MDLs for individual PAH analytes and biomarkers were determined to be less than 0.5 ng/g (ppb) dry weight and less than 5 ppb dry weightfor individual alkanes. Similar results were obtained when the sediment was spiked with the 16 EPA priority pollutants. In addition, a method has been developed to estimate MDLs for source-specific alkylated PAH analytes and chemical biomarker compounds for which standards are not commercially available or are prohibitively expensive. These improved analytical techniques have been used to identify and quantify low levels of hydrocarbons, derived from both natural and anthropogenic sources, found in the benthic sediments of Prince William Sound, AK.

The application of petroleum geochemistry to determining the fate and effects of oil spills in the marine environment requires high quality data to allow source identification through fingerprinting methods and unbiased sampling designs that allow valid comparisons to be made to detect spill related effects in the presence of other sources of environmental stress. This is particularly important in long-term studies, where sources of hydrocarbons and other pollutants unrelated to the spill event and non-spill related environmental effects become far more important in defining the environmental status of the spill zone. In studies of the Exxon Valdez oil spill, petroleum geochemistry is used to identify the many sources contributing polycyclic aromatic hydrocarbons (PAH) to the marine environment of Prince William Sound (PWS), including the Exxon Valdez oil spill, oil seep residues, particulates from eroding organic shales and coal formations, forest fire fallout, recent biogenic inputs and past human and industrial activities. A sediment quality triad-based shoreline ecology program (SEP), begun in 1990, includes a random sampling component and worst-case non-random site component that provides chemistry data through 2001 to determine the fate and bioavailability of spill oil residues on the shorelines. Environmental half-life values for the PAH at oiled sites range from 2.0 – 7.4 months for upper intertidal areas. Analysis of mussel tissue samples collected at worst-case spill locations find PAH concentrations in the same range as reference site samples. The results of concurrent sediment toxicity measurements using standard bioassays defines a dose-response relationship for total PAH concentration (TPAH) having a threshold of effect TPAH of 2,600 ng/g (dry wt.) that agrees well with the onset of sublethal ecological stress as defined by reductions in infaunal community structure parameters.

Analytical data must be reliable. Chemical fingerprinting methods, whether based on sample-specific comparisons of profiles, analyses of “diagnostic ratios,” or multivariate statistical analyses, are dependent on good quality analytical chemistry data and are thus vulnerable to data quality problems. Analytical data for the same compounds, but from different laboratories or derived by different methods, can introduce uncertainty in the comparisons. There are many chemical fingerprinting methods, which range from simple profile comparisons of individual samples to sophisticated multivariate analyses. Individual profile comparisons can be useful when the profiles are clearly different. However, the human eye has difficulty detecting subtle patterns between histogram plots of 10 PCDD/F homologs. Multivariate statistical analyses such as hierarchical cluster analysis and PCA are often used to condense and simplify a complex set of variables. These widely used and accepted techniques are scientifically defensible, although the underlying mathematics are complex.

Environmental forensics combines scientific disciplines and historical research methods to reconstruct past contaminating events, in particular, the parties involved and when and how contamination at various locations occurred. This overview of some applications of environmental forensics is based on laws and practices of the United States; however, the methods and framework should be applicable under a variety of international laws. Applications described include apportionment of responsibility for remediation of Superfund and other hazardous waste sites, site investigations for property transfer, environmental litigation between an insured party and insurers, and determination of the causes of personal injury in the context of a toxic tort.

AIMS To show the ability of magnetic resonance hydrometry (MRH) to quantify the pancreatic secretion after secretin stimulation in order to distinguish between physiological excretion and reduced output in chronic pancreatitis. METHODS MRH images were acquired in a 1.0-T-clinical scanner using a body-array coil and a heavily T2-weighted standard single-shot TSE sequence. Thirty-one patients (14 male/17 female) who routinely underwent ERCP for suspected choledocholithiasis (n = 22), recurring abdominal pain (n = 1), icterus (n = 6 and suspected pancreatitis (n = 2) were included. During the investigation 1 CU/kg BW secretin were administered intravenously. Secreted volume of fluid, start of secretion, achievement of a plateau of secretion and a combined score of these parameters (MRH score) were assessed and evaluated. Sensitivity and specificity were calculated for these parameters. RESULTS 27 patients had no pancreatic pathology, and four suffered from chronic pancreatitis. Patients without pancreatic disorders produced a mean pancreatic fluid volume of 183 plus minus 86 mL, whereas patients with chronic pancreatitis secreted 61 +/- 39 mL. Secretion started after a mean time of 95 +/- 94 seconds (no pancreatic impairment) and 62 +/- 13 seconds (chronic pancreatitis). The MRH score achieved a high accuracy in the detection of chronic pancreatitis. CONCLUSIONS Our study demonstrated the feasibility of measuring pancreatic output by MRH after stimulation with secretin. Moreover, a distinction between normal secretion and patients with chronic pancreatitis is possible.

The dominant sources of the petrogenic hydrocarbon background in benthic sediments of Prince William Sound, AK (PWS), site of the 1989 Exxon-Valdez oil spill, are eroding Tertiary shales and residues of natural oil seepage. Mass balance considerations and statistical analyses of hydrocarbon fingerprints independently indicate that coal contributes generally less than 1% of the polycyclic aromatic hydrocarbons (PAH) and chemical biomarkers in this background. This is environmentally significant because of presumed differences in the bioavailability of PAH in coal, seep oil residues, and shales. Coal particles are present in PWS sediments, but their PAH and chemical biomarker contributions are overwhelmed by those of seep oil residues and organic particles from shales of low-to-high thermally maturity. In the late Tertiary or early Quaternary, the currently exposed and eroding shale formations were heated into the oil-generation window and, consequently, are now relatively rich in extractable PAH and chemical biomarkers. The exposed and eroding coals in the area, in contrast, experienced long hot burial and are now thermally overmature with respect to oil generation. The concentrations of thermally sensitive PAH and biomarker compounds in PWS sediments are not consistent with a mature coal origin but are consistent with the low-to-high maturity shales and seep oils in the area.

This comment addresses the recent paper by Hostettler et al. proposing a new geochemical refractory PAH index, T/C (the ratio of triaromatic steranes to methyl chrysenes), and using the index to indicate that coal is the main source of the natural petrogenic hydrocarbons in marine sediments in Prince William Sound, Alaska. In response Bench et al. argue that coal is only one of several possibilities, and that measurements of vitrinite/kerogen reflectance, hydrocarbon mass balance calculations, and other molecular indicators including biomarkers demonstrate that coal is not the dominant source. The small sample of data used by Hostettler et al., evidence from vitrinite/kerogen reflectance data, beach coal, mass balance constraints, and the limitations of the T/C index are discussed. Selected molecular parameters in the sediments and in the potential sources of the hydrocarbons background are tabulated.

Thalassemias occur in individuals of all ethnic backgrounds and are among the most common genetic diseases worldwide. The diagnosis of thalassemia can easily be part of primary medical practice. Here we outline a practical approach to the detection of thalassemias in three common clinical settings. The first involves any patient with a low mean corpuscular volume (MCV) with or without anemia. The second is a neonatal screening result indicating possible presence of thalassemia. Finally, evaluation for thalassemia should be considered in the context of family planning or pregnancy in patients whose ethnicity indicates origin from high risk geographic areas. We also review the various types of the thalassemia syndromes and provide an overview of general therapeutic considerations.

In the article by White et al. (1) we find that the authors prematurely linked the condition of a single coral community to the Deepwater Horizon oil spill, without evaluating other plausible explanations, including the presence of natural oil and gas seeps near the coral, and the potential for underwater landslides to carry seep sediments onto the coral.

Background: Biomarkers of the immune system are currently not used as prognostic factors in breast cancer. We analyzedthe association of the B cell/plasma cell marker immunoglobulin kappa C (IGKC) and survival of untreated node-negative breast cancer patients.Material and Methods: IGKC expression was evaluated by immunostaining in a cohort of 335 node-negative breast cancer patients with a median follow-up of 152 months. The prognostic significance of IGKC for disease-free survival (DFS) and breast cancer-specific overall survival (OS) was evaluated with Kaplan-Meier survival analysis as well as univariate and multivariate Cox analysis adjusted for age at diagnosis, pT stage, histological grade, estrogen receptor (ER) status, progesterone receptor (PR) status, Ki-67 and human epidermal growth factor receptor 2 (HER-2) status.Results: 160 patients (47.7%) showed strong expression of IGKC. Univariate analysis showed that IGKC was significantlyassociated with DFS (P = 0.017, hazard ratio [HR] = 0.570, 95% confidence interval [CI] = 0.360–0.903) and OS (P = 0.011, HR = 0.438, 95% CI = 0.233–0.822) in the entire cohort. The significance of IGKC was especially strong in ER negative and in luminal B carcinomas. In multivariate analysis IGKC retained its significance independent of established clinical factors for DFS (P = 0.004, HR = 0.504, 95% CI = 0.315–0.804) as well as for OS (P = 0.002, HR = 0.371, 95% CI = 0.196–0.705).Conclusion: Expression of IGKC has an independent protective impact on DFS and OS in node-negative breast cancer.

The sonographic finding of increased echogenicity within the fetal abdomen presents a diagnostic dilemma, with a differential diagnosis ranging from normal variation to CF. We report the diagnostic evaluation of four cases, two of which were found to be the result of CF. On the basis of this experience, we believe that persistence of an echogenic bowel pattern, especially with bowel dilation, after 20 weeks' gestation should prompt an evaluation for CF. Using DNA analysis, approximately 75% of the cases involving CF can be detected with noninvasive studies of the parents, and confirmation by amniocentesis is performed only in those cases in which both parents are carriers of known mutations.

The long-term goals of our research are to understand the biochemical morbidity surrounding obstructive sleep apnea syndrome to define better the need for treatment and to determine modifiable risk factors for the disease. Our current hypothesis is that sleep-related hypoxemia results in alterations in metabolic regulatory peptides, specifically insulin and insulin-like growth factors (IGF-1 and IGF-2), which are known or suspected factors for obesity and disorders such as hypertension, glucose intolerance, and atherosclerosis. Surveys of clinic populations suggest a relationship between body habitus, parameters of sleep-disordered breathing, indices of oxygenation, and insulin resistance, defined by fasting serum levels of glucose and insulin. Results will provide insight into the role of metabolic regulatory peptides in the pathogenesis of sleep-disordered breathing and the mechanisms for this association.

Aroclor 1242 contains a high percentage of lightly chlorinated congeners, which makes it susceptible to congener profile alterations as a result of physical-chemical environmental weathering by water washing, evaporation, and volatilization. The analysis of the variability of congener profiles in paper sludge samples using PCA, mixing models, and correlation (R(2)) analysis, provided an integrated description of the behavior of Aroclor 1242 after its release in the environment. The results showed that the total PCB concentration decreased as the sample experienced weathering, with the congener profile of Aroclor 1242 shifting towards resembling heavier Aroclors as lighter congeners were lost. Mixing model analysis confirmed that a sample containing weathered Aroclor 1242 could easily be misidentified by laboratories as containing a mix of heavier Aroclors. The R(2) analysis showed that the profile of the congeners within a homologue group remained the same after weathering. This analysis showed that congeners that belong to the same level of chlorination behave similarly in such a manner that retains their overall profile when exposed to physical weathering.

Continued changes in climate are probable under most future scenarios. However, the magnitudes and timing of these changes are uncertain and will vary on a regional basis. Impacts of these changes on the oil and gas industry will play out on more local scales. Therefore, planning by HSE managers for impacts of climate change on the industry's plans and operations needs to incorporate the uncertainties in forecasts, a consideration of regional variations, and a translation to local consequences. This article outlines a step-wise approach for generating the information needed to assess risks and make informed decisions in the future. These decisions will be influenced by a host of environmental and legal drivers. The relative importance of those drivers will depend on a company's operations and locations. Therefore, an effective approach for planning must integrate operational information with relevant climate projections. The paper describes a scenario approach that yields a range of outcomes with associated likelihoods and consequences for the business. This approach demands that excellent communication occur between the decision makers and the analysts, to ensure high utility of information. We provide one example that involves alternative designs for oil and gas transport in relation to severe weather events.