Improving vitamin D content in pork meat by UVB biofortification.

Vitamin D deficiency is prevalent worldwide and identification of alternative food-based strategies are urgently warranted. In two studies, 12-week old crossbred pigs (Duroc x (Large White x Landrace)) were exposed daily to narrowband UVB radiation for ∼10 weeks or control (no UVB exposure) until slaughter. In Study 1 (n = 48), pigs were exposed to UVB for 2 min and in Study 2 (n = 20), this duration was tripled to 6 min. All pigs were fed the maximum permitted 2000 IU vitamin D3/kg feed. Loin meat was cooked prior to vitamin D LC-MS/MS analysis. In Study 1, pork loin vitamin D3 did not differ between groups. Study 2 provided longer UVB exposure time and resulted in significantly higher loin vitamin D3 (11.97 vs. 6.03 µg/kg), 25(OH)D3 (2.09 vs. 1.65 µg/kg) and total vitamin D activity (22.88 vs. 14.50 µg/kg) concentrations, compared to control (P < 0.05). Pigs remained healthy during both studies and developed no signs of erythema. Biofortification by UVB radiation provides an effective strategy to further safely increase the naturally occurring vitamin D content of pork loin, alongside feed supplementation.

Alkylidene Carbene from Silyl Vinyl Iodide Provides Mechanistic Insights on Trimethylenemethane Diyl-Mediated Tandem Cyclizations.

We describe a method to generate alkylidene carbenes via tetramethylammonium-fluoride-induced desilylation of silyl vinyl iodides. The reversible carbene generation from an iodovinyl anion enabled us to unearth mechanistic aspects of the trimethylenemethane (TMM) diyl cyclization reaction that could not be explored via previous methods. We observed that a slow diyl-diylophile cycloaddition can induce the reversible formation of an alkylidene carbene from the TMM diyl intermediate via a retro-cyclopropanation at ambient temperature.

Versatile Tools for Understanding Electrosynthetic Mechanisms.

Electrosynthesis is a popular, green alternative to traditional organic methods. Understanding the mechanisms is not trivial yet is necessary to optimize reaction processes. To this end, a multitude of analytical tools is available to identify and quantitate reaction products and intermediates. The first portion of this review serves as a guide that underscores electrosynthesis fundamentals, including instrumentation, electrode selection, impacts of electrolyte and solvent, cell configuration, and methods of electrosynthesis. Next, the broad base of analytical techniques that aid in mechanism elucidation are covered in detail. These methods are divided into electrochemical, spectroscopic, chromatographic, microscopic, and computational. Technique selection is dependent on predicted reaction pathways and electrogenerated intermediates. Often, a combination of techniques must be utilized to ensure accuracy of the proposed model. To conclude, future prospects that aim to enhance the field are discussed.

Addition of Lenalidomide to R-CHOP Improves Outcomes in Newly Diagnosed Diffuse Large B-Cell Lymphoma in a Randomized Phase II US Intergroup Study ECOG-ACRIN E1412.

PURPOSE: Lenalidomide combined with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) (R2CHOP) in untreated diffuse large B-cell lymphoma (DLBCL) has shown promising activity, particularly in the activated B-cell-like (ABC) subtype. Eastern Cooperative Oncology Group (ECOG)-ACRIN trial E1412 was a randomized phase II study comparing R2CHOP versus R-CHOP in untreated DLBCL. PATIENTS AND METHODS: Patients with newly diagnosed DLBCL, stage II bulky-IV disease, International Prognostic Index (IPI) ≥ 2, and ECOG performance status ≤ 2 were eligible and randomly assigned 1:1 to R2CHOP versus R-CHOP for six cycles. Tumors were analyzed using the NanoString Lymph2Cx for cell of origin. The primary end point was progression-free survival (PFS) in all patients with the co-primary end point of PFS in ABC-DLBCL. Secondary end points included overall response rate (ORR), complete response (CR) rate, and overall survival (OS). RESULTS: Three hundred forty-nine patients were enrolled; 280 patients (145 R2CHOP and 135 R-CHOP) were evaluable: 94 were ABC-DLBCL, 122 germinal center B-cell-like-DLBCL, 18 unclassifiable, and 46 unknowns. Baseline characteristics were well-balanced between arms, and the median age was 66 (range, 24-92); 70% of patients had stage IV disease; 34%, 43%, and 24% had IPI 2, 3, and 4 or 5, respectively. Myelosuppression was more common in the R2CHOP arm. The ORR and CR rate were 92% and 68% in R-CHOP and 97% (P = .06) and 73% (P = .43) in the R2CHOP arm, respectively. The median follow-up was 3.0 years; R2CHOP was associated with a 34% reduction in risk of progression or death versus R-CHOP (hazard ratio [HR], 0.66 95% CI, 0.43 to 1.01) and 3-year PFS of 73% versus 61%, one-sided P = .03, and an improvement in OS (83% and 75% at 3 years; HR, 0.67; one-sided P = .05). The PFS HR for R2CHOP was 0.67 for ABC-DLBCL, one-sided P = .1. CONCLUSION: In this signal-seeking study, the addition of lenalidomide to R-CHOP (R2CHOP) improved outcomes in newly diagnosed DLBCL including patients with ABC-DLBCL.

A Perspective on Organic Electrochemistry.

The author describes perspectives gained over many years of engagement in the field of organic electrochemistry. The manuscript will hopefully dispel a number of misconceptions and provide a framework for thinking about how electrochemistry can be uniquely applied to solving problems in synthesis and to obtaining mechanistic insights.

The Doctor Can See You Now: A Key Stakeholder Study Into The Acceptability Of Ambulance Based Telemedicine.

Using telecommunications technology it would be possible to link a patient and paramedic to a Doctor in the Emergency Department (ED) at the point of first patient contact. A questionnaire-based study on telemedicine in the pre-hospital environment involving patients, paramedics, doctors and nurses in the ED, was performed to assess if they would want and accept telemedicine in pre-hospital emergency care. When asked 98.5% (55) of patients, 89% (11) of doctors, 76% (14) of nurses and 91% (42) of ambulance personnel saw the potential of an audio-visual link from the pre-hospital environment to the ED. The potential benefits were felt to be in diagnosis of time-dependent illnesses, time management, increased hospital preparedness for incoming patients and increased triage efficiency. Stakeholder enthusiasm for pre-hospital telemedicine must be met with the technological requirements to provide such a service. As noted by one patient a pre-hospital audio-visual link to the ED could be "potentially a life saving service".

A new method for the high-precision assessment of tumor changes in response to treatment.

Motivation: Imaging demonstrates that preclinical and human tumors are heterogeneous, i.e. a single tumor can exhibit multiple regions that behave differently during both development and also in response to treatment. The large variations observed in control group, tumors can obscure detection of significant therapeutic effects due to the ambiguity in attributing causes of change. This can hinder development of effective therapies due to limitations in experimental design rather than due to therapeutic failure. An improved method to model biological variation and heterogeneity in imaging signals is described. Specifically, linear Poisson modeling (LPM) evaluates changes in apparent diffusion co-efficient between baseline and 72 h after radiotherapy, in two xenograft models of colorectal cancer. The statistical significance of measured changes is compared to those attainable using a conventional t-test analysis on basic apparent diffusion co-efficient distribution parameters. Results: When LPMs were applied to treated tumors, the LPMs detected highly significant changes. The analyses were significant for all tumors, equating to a gain in power of 4-fold (i.e. equivalent to having a sample size 16 times larger), compared with the conventional approach. In contrast, highly significant changes are only detected at a cohort level using t-tests, restricting their potential use within personalized medicine and increasing the number of animals required during testing. Furthermore, LPM enabled the relative volumes of responding and non-responding tissue to be estimated for each xenograft model. Leave-one-out analysis of the treated xenografts provided quality control and identified potential outliers, raising confidence in LPM data at clinically relevant sample sizes. Availability and implementation: TINA Vision open source software is available from www.tina-vision.net. Supplementary information: Supplementary data are available at Bioinformatics online.

High turnover in electro-oxidation of alcohols and ethers with a glassy carbon-supported phenanthroimidazole mediator.

Glassy carbon electrodes covalently modified with a phenanthroimidazole mediator promote electrochemical alcohol and ether oxidation: three orders of magnitude increase in TON, to ∼15 000 in each case, was observed compared with homogeneous mediated reactions. We propose the deactivation pathways in homogeneous solution are prevented by the immobilization: modified electrode reversibility is increased for a one-electron oxidation reaction. The modified electrodes were used to catalytically oxidize p-anisyl alcohol and 1-((benzyloxy)methyl)-4-methoxybenzene, selectively, to the corresponding benzaldehyde and benzyl ester, respectively.

International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017).

In recent years, the number of approved and investigational agents that can be safely administered for the treatment of lymphoma patients for a prolonged period of time has substantially increased. Many of these novel agents are evaluated in early-phase clinical trials in patients with a wide range of malignancies, including solid tumors and lymphoma. Furthermore, with the advances in genome sequencing, new "basket" clinical trial designs have emerged that select patients based on the presence of specific genetic alterations across different types of solid tumors and lymphoma. The standard response criteria currently in use for lymphoma are the Lugano Criteria which are based on [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography or bidimensional tumor measurements on computerized tomography scans. These differ from the RECIST criteria used in solid tumors, which use unidimensional measurements. The RECIL group hypothesized that single-dimension measurement could be used to assess response to therapy in lymphoma patients, producing results similar to the standard criteria. We tested this hypothesis by analyzing 47 828 imaging measurements from 2983 individual adult and pediatric lymphoma patients enrolled on 10 multicenter clinical trials and developed new lymphoma response criteria (RECIL 2017). We demonstrate that assessment of tumor burden in lymphoma clinical trials can use the sum of longest diameters of a maximum of three target lesions. Furthermore, we introduced a new provisional category of a minor response. We also clarified response assessment in patients receiving novel immune therapy and targeted agents that generate unique imaging situations.

Developing a risk-based trading scheme for cattle in England: farmer perspectives on managing trading risk for bovine tuberculosis.

This paper examines farmer attitudes towards the development of a voluntary risk-based trading scheme for cattle in England as a risk mitigation measure for bovine tuberculosis (bTB). The research reported here was commissioned to gather evidence on the type of scheme that would have a good chance of success in improving the information farmers receive about the bTB risk of cattle they buy. Telephone interviews were conducted with a stratified random sample of 203 cattle farmers in England, splitting the interviews equally between respondents in the high-risk area and low-risk area for bTB. Supplementary interviews and focus groups with farmers were also carried out across the risk areas. Results suggest a greater enthusiasm for a risk-based trading scheme in low-risk areas compared with high-risk areas and among members of breed societies and cattle health schemes. Third-party certification of herds by private vets or the Animal and Plant Health Agency were regarded as the most credible source, with farmer self-certification being favoured by sellers, but being regarded as least credible by buyers. Understanding farmers' attitudes towards voluntary risk-based trading is important to gauge likely uptake, understand preferences for information provision and to assist in monitoring, evaluating and refining the scheme once established.

Compensation and exotic livestock disease management: the views of animal keepers and veterinarians in England.

Relatively little is known about the perceived influence of different compensation systems on animal keepers' management of exotic livestock disease. This paper aims to address this research gap by drawing on interviews with 61 animal keepers and 21 veterinarians, as well as a series of nine animal keeper focus groups across five different livestock sectors in England. The perceived influence of current compensation systems on disease control behaviour was explored and alternative compensation systems that respectively reward positive practices and penalise poor practices were presented in the form of scenarios, alongside a third system that considered the option of a cost-sharing levy system between industry and government. The results indicate that animal keepers consider themselves to be influenced by a range of non-financial factors, for example, feelings of responsibility, reputation and animal welfare concerns, in the context of their exotic disease management practices. The majority of animal keepers were unaware of the current compensation systems in place for exotic diseases, and were therefore not consciously influenced by financial recompense. Concerns were raised about linking compensation to disease management behaviour due to auditing difficulties. A cost-sharing levy system would likely raise awareness of exotic disease and compensation among animal keepers, but differentiation of payments based upon individual farm-level risk assessments was called for by participants as a strategy to promote positive disease management practices.

Electrochemical Oxidative Amination of Sodium Sulfinates: Synthesis of Sulfonamides Mediated by NH4I as a Redox Catalyst.

An efficient protocol for the synthesis of sulfonamides via the electrochemical oxidative amination of sodium sulfinates has been developed. The chemistry proceeds in a simple undivided cell employing a substoichiometric amount of NH4I that serves both as a redox catalyst and a supporting electrolyte; in this manner additional conducting salt is not required. A wide range of substrates, including aliphatic or aromatic secondary and primary amines, as well as aqueous ammonia, proved to be compatible with the protocol. Scale-up was possible, thereby demonstrating the practicality of the approach. The electrolytic process avoids the utilization of external oxidants or corrosive molecular iodine and therefore represents an environmentally benign means by which to achieve the transformation.

Aromatic C-H Bond Functionalization Induced by Electrochemically in Situ Generated Tris(p-bromophenyl)aminium Radical Cation: Cationic Chain Reactions of Electron-Rich Aromatics with Enamides.

An effective Friedel-Crafts alkylation reaction of electron-rich aromatics with N-vinylamides, induced by electrochemically in situ-generated TBPA radical cation, has been developed; the resulting adducts are produced in good to excellent yields. In the "ex-cell" type electrolysis, TBPA is transformed to its oxidized form in situ and subsequently employed as an electron transfer reagent to initiate a cationic chain reaction. An easily recoverable and reusable polymeric ionic liquid-carbon black (PIL-CB) composite was also utilized as a supporting electrolyte for the electrochemical generation of TBPA cation radical, without sacrificing efficiency or stability after four electrolyses. Cyclic voltammetry analysis and the results of control experiments demonstrate that the reaction of electron-rich aromatics and N-vinylamides occurs via a cationic chain reaction, which takes place though an oxidative activation of a C-H bond of electron-rich aromatics instead of oxidation of the N-vinylamide as previously assumed.

Electrocatalytic aziridination of alkenes mediated by n-Bu4NI: a radical pathway.

Efficient electrocatalytic aziridination of alkenes has been achieved for the first time. A structurally broad range of aziridines was easily accessed using an undivided cell operated at constant current and mediated by a catalytic quantity of n-Bu4NI. The electrocatalytic reaction also proceeded in the absence of additional conducting salt. The aziridination is proposed to follow a radical mechanism.

Polymeric ionic liquid and carbon black composite as a reusable supporting electrolyte: modification of the electrode surface.

One of the major impediments to using electroorganic synthesis is the need for large amounts of a supporting electrolyte to ensure the passage of charge. Frequently this causes separation and waste problems. To address these issues, a polymeric ionic liquid-Super P carbon black composite has been formulated. The system enables electrolyses to be performed without adding an additional supporting electrolyte, and its efficient recovery and reuse. In addition, the ability of the composite to modify the electrode surface in situ leads to improved kinetics. A practical consequence is that one can decrease catalyst loading without sacrificing efficiency.

Changes in the influence of lymphoma- and HIV-specific factors on outcomes in AIDS-related non-Hodgkin lymphoma.

BACKGROUND: We undertook the present analysis to examine the shifting influence of prognostic factors in HIV-positive patients diagnosed with aggressive non-Hodgkin lymphoma (NHL) over the last two decades. PATIENTS AND METHODS: We carried out a pooled analysis from an existing database of patients with AIDS-related lymphoma. Individual patient data had been obtained prior from prospective phase II or III clinical trials carried out between 1990 until 2010 in North America and Europe that studied chemo(immuno)therapy in HIV-positive patients diagnosed with AIDS-related lymphomas. Studies had been identified by a systematic review. We analyzed patient-level data for 1546 patients with AIDS-related lymphomas using logistic regression and Cox proportional hazard models to identify the association of patient-, lymphoma-, and HIV-specific variables with the outcomes complete response (CR), progression-free survival, and overall survival (OS) in different eras: pre-cART (1989-1995), early cART (1996-2000), recent cART (2001-2004), and contemporary cART era (2005-2010). RESULTS: Outcomes for patients with AIDS-related diffuse large B-cell lymphoma and Burkitt lymphoma improved significantly over time, irrespective of baseline CD4 count or age-adjusted International Prognostic Index (IPI) risk category. Two-year OS was best in the contemporary era: 67% and 75% compared with 24% and 37% in the pre-cART era (P < 0.001). While the age-adjusted IPI was a significant predictor of outcome in all time periods, the influence of other factors waxed and waned. Individual HIV-related factors such as low CD4 counts (<50/mm(3)) and prior history of AIDS were no longer associated with poor outcomes in the contemporary era. CONCLUSIONS: Our results demonstrate a significant improvement of CR rate and survival for all patients with AIDS-related lymphomas. Effective HIV-directed therapies reduce the impact of HIV-related prognostic factors on outcomes and allow curative antilymphoma therapy for the majority of patients with aggressive NHL.

Understanding the elevated suicide risk of female soldiers during deployments.

BACKGROUND: The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) has found that the proportional elevation in the US Army enlisted soldier suicide rate during deployment (compared with the never-deployed or previously deployed) is significantly higher among women than men, raising the possibility of gender differences in the adverse psychological effects of deployment. METHOD: Person-month survival models based on a consolidated administrative database for active duty enlisted Regular Army soldiers in 2004-2009 (n = 975,057) were used to characterize the gender × deployment interaction predicting suicide. Four explanatory hypotheses were explored involving the proportion of females in each soldier's occupation, the proportion of same-gender soldiers in each soldier's unit, whether the soldier reported sexual assault victimization in the previous 12 months, and the soldier's pre-deployment history of treated mental/behavioral disorders. RESULTS: The suicide rate of currently deployed women (14.0/100,000 person-years) was 3.1-3.5 times the rates of other (i.e. never-deployed/previously deployed) women. The suicide rate of currently deployed men (22.6/100,000 person-years) was 0.9-1.2 times the rates of other men. The adjusted (for time trends, sociodemographics, and Army career variables) female:male odds ratio comparing the suicide rates of currently deployed v. other women v. men was 2.8 (95% confidence interval 1.1-6.8), became 2.4 after excluding soldiers with Direct Combat Arms occupations, and remained elevated (in the range 1.9-2.8) after adjusting for the hypothesized explanatory variables. CONCLUSIONS: These results are valuable in excluding otherwise plausible hypotheses for the elevated suicide rate of deployed women and point to the importance of expanding future research on the psychological challenges of deployment for women.

Electrochemically induced ring-opening/Friedel­Crafts arylation of chalcone epoxides catalyzed by a triarylimidazole redox mediator.

The indirect anodic oxidation of chalcone epoxides in the presence of electron-rich heteroarenes mediated by a triarylimidazole (Med) was investigated by cyclic voltammetry (CV) and controlled potential electrolysis. The CV results indicate that a homogeneous electron transfer between Med•+ and chalcone epoxides is facilitated by an electron-rich heteroarene that serves as an arylation reagent. The preparative scale electrolysis generated epoxide-ring-opened/Friedel­Crafts arylation products in moderate to good yields. The fact that only a catalytic amount of charge was required suggests that Med•+ initiates a chain reaction. In addition, overoxidation of the products is avoided even though their oxidation potential is less than that of the starting chalcone epoxides.