Priority research questions for the UK food system

The rise of food security up international political, societal and academic agendas has led to increasing interest in novel means of improving primary food production and reducing waste. There are however, also many 'post-farm gate' activities that are critical to food security, including processing, packaging, distributing, retailing, cooking and consuming. These activities all affect a range of important food security elements, notably availability, affordability and other aspects of access, nutrition and safety. Addressing the challenge of universal food security, in the context of a number of other policy goals (e.g. social, economic and environmental sustainability), is of keen interest to a range of UK stakeholders but requires an up-to-date evidence base and continuous innovation. An exercise was therefore conducted, under the auspices of the UK Global Food Security Programme, to identify priority research questions with a focus on the UK food system (though the outcomes may be broadly applicable to other developed nations). Emphasis was placed on incorporating a wide range of perspectives ('world views') from different stakeholder groups: policy, private sector, non-governmental organisations, advocacy groups and academia. A total of 456 individuals submitted 820 questions from which 100 were selected by a process of online voting and a three-stage workshop voting exercise. These 100 final questions were sorted into 10 themes and the 'top' question for each theme identified by a further voting exercise. This step also allowed four different stakeholder groups to select the top 7-8 questions from their perspectives. Results of these voting exercises are presented. It is clear from the wide range of questions prioritised in this exercise that the different stakeholder groups identified specific research needs on a range of post-farm gate activities and food security outcomes. Evidence needs related to food affordability, nutrition and food safety (all key elements of food security) featured highly in the exercise. While there were some questions relating to climate impacts on production, other important topics for food security (e.g. trade, transport, preference and cultural needs) were not viewed as strongly by the participants.

Modelling a light-driven phytoplankton succession

We used a numerical model to investigate if and to what extent cellular photoprotective capacity accounts for succession and vertical distribution of marine phytoplankton species/groups. A model describing xanthophyll photoprotective activity in phytoplankton has been implemented in the European Regional Sea Ecosystem Model and applied at the station L4 in the Western English Channel. Primary producers were subdivided into three phytoplankton functional types defined in terms of their capacity to acclimate to different light-specific environments: low light (LL-type), high light (HL-type) and variable light (VL-type) adapted species. The LL-type is assumed to have low cellular level of xanthophyll-cycling pigments (PX) relative to the modelled photosynthetically active pigments (chlorophyll and fucoxanthin (FUCO) = PSP). The HL-type has high PX content relative to PSP while VL-type presents an intermediate PX to PSP ratio. Furthermore, the VL-type is capable of reversibly converting FUCO to PX and synthesizing new PX under high-light stress. In order to reproduce phytoplankton community succession with each of the three groups being dominant in different periods of the year, we had also to assume reduced grazing pressure on HL-adapted species. Model simulations realistically reproduce the observed seasonal patterns of pigments and nutrients highlighting the reasonability of the underpinning assumptions. Our model suggests that pigment-mediated photophysiology plays a primary role in determining the evolution of marine phytoplankton communities in the winter-spring period corresponding to the shoaling of the mixed layer and the increase of light intensity. Grazing selectivity however contributes to the phytoplankton community composition in summer.

The future of the northeast Atlantic benthic flora in a high CO2 world

Seaweed and seagrass communities in the northeast Atlantic have been profoundly impacted by humans, and the rate of change is accelerating rapidly due to runaway CO2 emissions and mounting pressures on coastlines associated with human population growth and increased consumption of finite resources. Here, we predict how rapid warming and acidification are likely to affect benthic flora and coastal ecosystems of the northeast Atlantic in this century, based on global evidence from the literature as interpreted by the collective knowledge of the authorship. We predict that warming will kill off kelp forests in the south and that ocean acidification will remove maerl habitat in the north. Seagrasses will proliferate, and associated epiphytes switch from calcified algae to diatoms and filamentous species. Invasive species will thrive in niches liberated by loss of native species and spread via exponential development of artificial marine structures. Combined impacts of seawater warming, ocean acidification, and increased storminess may replace structurally diverse seaweed canopies, with associated calcified and noncalcified flora, with simple habitats dominated by noncalcified, turf-forming seaweeds.

Conservative Interventions for mobile Pes Planus in Adults: a systematic review

Antecedentes. Pes Adulto planus (pie plano) es un problema común encontrado por muchos profesionales de la salud. A pesar de la percepción de que el pie plano puede causar dolor y deteriorar su función, la disponibilidad y el uso generalizado de diversos tratamientos, no hay consenso sobre la estrategia óptima de tratamiento. Objetivo. Evaluar la efectividad de las intervenciones conservadoras (no quirúrgicos) para pie plano en los adultos. Método. Se realizó una búsqueda sistemática de la literatura. Esto incluye: el Registro Cochrane Central de Ensayos Controlados; los Juicios CMSG Especializados Registro; una búsqueda electrónica se realizó utilizando MEDLINE (1960 a junio de 2012), EMBASE (1980 a junio de 2012), y CINAHL (1982 - junio de 2012). Revistas especializadas, listas de referencias de ensayos y artículos de revisión se realizaron búsquedas manuales. Criterios de selección: Ensayos aleatorios o cuasialeatorios de intervenciones de tratamiento para el pie plano en los adultos. Se excluyeron los ensayos que incluyeron patologías específicas como el dolor plantar del talón, las fracturas por sobrecarga de los metatarsianos, disfunción del tendón tibial posterior-, fracturas de tobillo, patologías del pie reumatoide, enfermedades neuromusculares y las complicaciones del pie diabético. Recopilación y análisis de datos: Dos autores seleccionaron de forma independiente los resultados de la búsqueda para identificar a aquellos que satisfacen los criterios de inclusión y evaluaron la calidad de los incluidos mediante una lista de control basado en la Evaluación de la Colaboración Cochrane de Riesgo. Esta herramienta se centró en el riesgo de la selección, el rendimiento, la detección, la heterogeneidad y el sesgo de notificación. Resultados. Cuatro ensayos, con 140 sujetos, cumplieron los criterios de inclusión para la revisión. Los cuatro fueron juzgados como de alto riesgo de sesgo en al menos un área, y también estaban en riesgo de sesgo incierto en al menos otra zona. Todos anotaron altamente en relación al sesgo de deserción, debido al corto seguimiento tiempos y diseños experimentales utilizados. Los datos no se agruparon debido al alto nivel de heterogeneidad identificada en las intervenciones evaluadas, los participantes seleccionados y medir los resultados. Los resultados de un estudio sugieren que después de cuatro semanas de uso ortesis puede resultar en una mejora significativa en vaivén lateral medio, y pueden resultar en una mejor, aunque no significativa, en general relacionados con la calidad de vida de los pies (Roma 2004). Un estudio (Redmond 2009) sugiere que su efecto sobre la distribución de la presión plantar en el pie puede no depender de si son personalizados o dispositivos prefabricados. Aunque este estudio se identificaron cambios significativos en algunas variables de presión plantar tanto con la costumbre y dispositivos prefabricados, otro (Esterman 2005) no encontró ningún efecto significativo de longitud ¾ ortesis prefabricadas sobre el dolor, la incidencia de lesiones, salud pie o de calidad de vida en un grupo de reclutas de la fuerza aérea. El cuarto estudio (Jung 2009) sugiere que el ejercicio de los músculos intrínsecos del pie puede mejorar el efecto de las ortesis. A pesar de estos resultados, ya que cada estudio incurrió riesgo de sesgo en al menos un área no se pueden sacar conclusiones

Upin & Ipin: Promoting malaysian culture values through animation

Malaysian children lately have been exposed or influenced heavily by digital media entertainment. The rise of such entertainment tends to drive them away from understanding and appreciating the values of Malaysian culture. Upin and Ipin animation has successfully promoted Malaysian folklore culture and has significantly portrayed the art of Malaysian values including Islamic values by providing the platform for harmonious relationship among different societies or groups or religious backgrounds. The focus of this research is to look into the usage of Malaysian culture iconic visual styles such as backgrounds, lifestyles, character archetypes and narrative (storytelling). Therefore, we hope that this research will benefit the younger generation by highlighting the meaning and importance of implicit Malaysian culture.

Measles virus and classical Hodgkin lymphoma: no evidence for a direct association.

A proportion of Hodgkin lymphoma (HL) cases are causally associated with the Epstein-Barr virus (EBV) but the aetiology of the remaining cases remains obscure. Over the last 3 decades several studies have found an association between HL and measles virus (MV) including a recent cohort study describing the detection of MV antigens in Hodgkin and Reed-Sternberg cells, the tumour cells in HL. In the present study we looked at the relationship between history of MV infection and risk of developing HL in a population-based, case/control study of HL. In addition we used immunohistochemistry and RT-PCR to look for direct evidence of MV in HL biopsies. There was no significant difference in the proportion of cases reporting previous measles compared to controls in the entire data set or when young adults were considered separately. Using a robust immunohistochemical assay for MV infection, we failed to find evidence of MV in biopsies from 97 cases of HL and RT-PCR studies similarly gave negative results. This study therefore provides no evidence that MV is directly involved in the development of HL. However, when age at first reported MV infection was investigated, significant differences emerged with children infected before school-age having higher risk, especially of EBV-ve HL, when compared with children infected at older ages; the interpretation of these latter results is unclear.

Survival patterns among lymphoma patients with a family history of lymphoma

Purpose: Genetic factors are important in the etiology and pathogenesis of chronic lymphocytic leukemia (CLL), Hodgkin's lymphoma (HL), and non-Hodgkin's lymphoma (NHL). Only a few small studies have assessed clinical characteristics and prognosis for familial patients, with inconsistent findings. Methods: Using population-based registries from Sweden and Denmark, 7,749 patients with CLL, 7,476 patients with HL, and 25,801 patients with NHL with linkable first-degree relatives were identified. Kaplan-Meier curves were constructed to compare survival in patients with lymphoma with and without a family history of lymphoma. The risk of dying was assessed using adjusted Cox proportional hazard models. Results: We found 85 patients with CLL (1.10%), 95 patients with HL (1.28%), and 206 patients with NHL (0.80%) with a family history of any lymphoma. Five-year mortality was similar for patients with CLL (hazard ratio [HR], 1.28; 95% CI, 0.95 to 1.72), HL (HR, 0.78; 95% CI, 0.49 to 1.25), and NHL (HR, 0.91; 95% CI, 0.74 to 1.12) versus without a family history of any lymphoma. Mortality was also similar for patients with versus without a family history of the same lymphoma. T-cell/anaplastic lymphoma patients with a family history of NHL had poorer outcome 5-years after diagnosis (HR, 5.38; 95% CI, 1.65 to 17.52). Results were similar for 10 years of follow-up. Conclusion: With the exception of T-cell/anaplastic lymphoma, survival patterns for patients with CLL, HL, and NHL with a family history of lymphoma were similar to those for sporadic patients, suggesting that most familial lymphomas do not have an altered clinical course. Our findings provide no evidence to modify therapeutic strategies for patients with CLL, HL, or NHL based solely on family history. © 2008 by American Society of Clinical Oncology.


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Pulsating or not? A search for hidden pulsations below the red edge of the ZZ Ceti instability strip

The location of the red edge of the ZZ Ceti instability strip is defined observationally as being the lowest temperature for which a white dwarf with a H-rich atmosphere (DA) is known to exhibit periodic brightness variations. Whether this cut-off in flux variations is actually due to a cessation of pulsation or merely due to the attenuation of any variations by the convection zone, rendering them invisible, is not clear. The latter is a theoretical possibility because with decreasing effective temperature, the emergent flux variations become an ever smaller fraction of the amplitude of the flux variations in the interior. In contrast to the flux variations, the visibility of the velocity variations associated with the pulsations is not thought to be similarly affected. Thus, models imply that were it still pulsating, a white dwarf just below the observed red edge should show velocity variations. In order to test this possibility, we used time-resolved spectra of three DA white dwarfs that do not show photometric variability, but which have derived temperatures only slightly lower than the coolest ZZ Ceti variables. We find that none of our three targets show significant periodic velocity variations, and set 95% confidence limits on amplitudes of 3.0, 5.2, and 8.8 km s(-1). Thus, for two out of our three objects, we can rule out velocity variations as large as 5.4 km s(-1) observed for the strongest mode in the cool white dwarf pulsator ZZ Psc. In order to verify our procedures, we also examined similar data of a known ZZ Ceti, HL Tau 76. Applying external information from the light curve, we detect significant velocity variations for this object with amplitudes of up to 4 km s(-1). Our results suggest that substantial numbers of pulsators having large velocity amplitudes do not exist below the observed photometric red edge and that the latter probably reflects a real termination of pulsations.

Platinum(II) phosphine and orotate complexes with aminopyridine co-ligands, and their molecular recognition via hydrogen bonding

The new complexes [Pt(dppp)(py)(2)][OTf](2), 1, [Pt(dppp)(2-ap)(2)][OTf](2), 2, [(dppp)Pt(mu -OH){mu -NH(C5H3N)NH2}Pt(dppp)][OTf](2), 3 (py=pyridine, 2-ap=2-aminopyridine, NH(C5H3N)NH2=2,6-diaminopyridine anion, dppp = 1,3-bis(diphenylphosphino)propane, OTf=O3SCF3) have been prepared via reactions between [Pt(dppp)(OTf)(2)] and pyridine, 2-aminopyridine or 2,6-diaminopyridine (2,6-dap) respectively. The amines exhibit a range of co-ordination modes. Pyridine and 2-aminopyridine co-ordinate to platinum through endo-nitrogen atoms in complexes 1 and 2, the latter existing as a pair of rotomers due to the steric hindrance introduced by the 2-substituent. However, 2,6-diaminopyridine co-ordinates to platinum through the exo-nitrogen of one amino group, to give the unusual mu -amido complex 3. Reaction of the known orotate chelate complex [Pt(PEt3)(2)(N,O-HL)] [HL=orotate, the dianion of 2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid (orotic acid)] with 2,6-dap gave [Pt(PEt3)(2)(2,6-dap)(N-HL)] 4, which contains an unconventional monodentate orotate ligand. In this co-ordination mode the orotate retains an ADA hydrogen bonding site and was found to co-crystallise with 2,6-dap via complementary ADA:DAD triple hydrogen bonds to give [Pt(PEt3)(2)(N-HL)(2,6-dap)].2,6-dap, 5. Complex 5 exhibits a helical chain structure of associated [1+1] adducts in the solid state.

Orotate complexes of rhodium(I) and iridium(I): effect of coligand, counter ion, and solvent of crystallisation on association via complementary hydrogen bonding

The new complexes [NEt3H][M(HL)(cod)] (M = Rh 1 or Ir 2; H3L = 2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid, erotic acid; cod = cycloocta-1,5-diene) have been prepared by the reaction between [M2Cl2(cod)(2)] and erotic acid in dichloromethane in the presence of Ag2O and NEt3. They crystallise as dichloromethane adducts 1 . CH2Cl2 and 2 . CH2Cl2 from dichloromethane-hexane solutions. These isomorphous structures contain doubly hydrogen-bonded dimers, with additional hydrogen bonding to NEt3H+ cations and bridging CH2Cl2 molecules to form tapes. The use of (NBu4OH)-O-n instead of NEt3 gave the related complex [NBu4n][Rh(HL)(cod)] 1' which has an innocent cation not capable of forming strong hydrogen bonds and in contrast to 1 exists as discrete doubly hydrogen-bonded dimers. Complex 1' cocrystallises with 2,6-diaminopyridine (dap) via complementary triple hydrogen bonds to give [NBu4n][Rh(HL)(cod)]. dap . CH2Cl2 3. Complex 3 exhibits an extended sheet structure of associated [2 + 2] units, with layers of NBu4n, cations separating the sheets. These structural data together with those reported previously for platinum orotate complexes suggest that the steric requirements of the other ligands co-ordinated to the metal are important in influencing their hydrogen-bonding abilities. The solvent of crystallisation, the hydrogen-bonding propensity of the coligand and the nature of the counter ion also determine the type of association in the solid state.

Differential TERT promoter methylation and response to 5-aza-2'-deoxycytidine in acute myeloid leukemia cell lines:TERT expression, telomerase activity, telomere length, and cell death

The catalytic subunit of human telomerase (TERT) is highly expressed in cancer cells, and correlates with complex cytogenetics and disease severity in acute myeloid leukemia (AML). The TERT promoter is situated within a large CpG island, suggesting that expression is methylation-sensitive. Studies suggest a correlation between hypermethylation and TERT overexpression. We investigated the relationship between TERT promoter methylation and expression and telomerase activity in human leukemia and lymphoma cell lines. DAC-induced demethylation and cell death were observed in all three cell lines, as well as telomere shortening in HL-60 cells. DAC treatment reduced TERT expression and telomerase activity in OCI/AML3 and HL-60 cells, but not in U937 cells. Control U937 cells expressed lower levels of TERT mRNA, carried a highly methylated TERT core promoter, and proved more resistant to DAC-induced repression of TERT expression and cell death. AML patients had significantly lower methylation levels at several CpGs than "well elderly" individuals. This study, the first to investigate the relationship between TERT methylation and telomerase activity in leukemia cells, demonstrated a differential methylation pattern and response to DAC in three AML cell lines. We suggest that, although DAC treatment reduces TERT expression and telomerase activity, this is unlikely to occur via direct demethylation of the TERT promoter. However, further investigations on the regions spanning CpGs 7-12 and 14-16 may reveal valuable information regarding transcriptional regulation of TERT.

Common infection-related conditions and risk of lymphoid malignancies in older individuals

Background: Chronic antigenic stimulation may initiate non-Hodgkin (NHL) and Hodgkin lymphoma (HL) development. Antecedent, infection-related conditions have been associated, but evidence by lymphoproliferative subtype is limited. Methods: From the US SEER-Medicare database, 44 191 NHL, 1832 HL and 200 000 population-based controls, frequency-matched to all SEER cancer cases, were selected. Logistic regression models, adjusted for potential confounders, compared infection-related conditions in controls with HL and NHL patients and by the NHL subtypes diffuse large B-cell, T-cell, follicular and marginal zone lymphoma (MZL). Stratification by race was undertaken. Results: Respiratory tract infections were broadly associated with NHL, particularly MZL. Skin infections were associated with a 15–28% increased risk of NHL and with most NHL subtypes, particularly cellulitis with T-cell lymphoma (OR 1.36, 95%CI 1.24–1.49). Only herpes zoster remained associated with HL following Bonferroni correction (OR 1.55, 95% CI 1.28–1.87). Gastrointestinal and urinary tract infections were not strongly associated with NHL or HL. In stratified analyses by race, sinusitis, pharyngitis, bronchitis and cellulitis showed stronger associations with total NHL in blacks than whites (P<0.001). Conclusions: Infections may contribute to the aetiologic pathway and/or be markers of underlying immune modulation. Precise elucidation of these mechanisms may provide important clues for understanding how immune disturbance contributes to lymphoma.

The vascular targeting agent combretastatin-A4 and a novel cis-Restricted {beta}-Lactam Analogue, CA-432, induce apoptosis in human chronic myeloid leukemia cells and ex vivo patient samples including those displaying multidrug resistance

Combretastatin-A4 (CA-4) is a natural derivative of the African willow tree Combretum caffrum. CA-4 is one of the most potent antimitotic components of natural origin, but it is, however, intrinsically unstable. A novel series of CA-4 analogs incorporating a 3,4-diaryl-2-azetidinone (β-lactam) ring were designed and synthesized with the objective to prevent cis -trans isomerization and improve the intrinsic stability without altering the biological activity of CA-4. Evaluation of selected β-lactam CA-4 analogs demonstrated potent antitubulin, antiproliferative, and antimitotic effects in human leukemia cells. A lead β-lactam analog, CA-432, displayed comparable antiproliferative activities with CA-4. CA-432 induced rapid apoptosis in HL-60 acute myeloid leukemia cells, which was accompanied by depolymerization of the microtubular network, poly(ADP-ribose) polymerase cleavage, caspase-3 activation, and Bcl-2 cleavage. A prolonged G(2)M cell cycle arrest accompanied by a sustained phosphorylation of mitotic spindle checkpoint protein, BubR1, and the antiapoptotic proteins Bcl-2 and Bcl-x(L) preceded apoptotic events in K562 chronic myeloid leukemia (CML) cells. Molecular docking studies in conjunction with comprehensive cell line data rule out CA-4 and β-lactam derivatives as P-glycoprotein substrates. Furthermore, both CA-4 and CA-432 induced significantly more apoptosis compared with imatinib mesylate in ex vivo samples from patients with CML, including those positive for the T315I mutation displaying resistance to imatinib mesylate and dasatinib. In summary, synthetic intrinsically stable analogs of CA-4 that display significant clinical potential as antileukemic agents have been designed and synthesized.

Novel microtubule-targeting agents, pyrrolo-1,5-benzoxazepines, induce apoptosis in multi-drug-resistant cancer cells

PURPOSE: The development of multi-drug resistance (MDR) due to the expression of members of the ATP binding cassette (ABC) transporter family is a major obstacle in cancer treatment. The broad range of substrate specificities associated with these transporters leads to the efflux of many anti-cancer drugs from tumour cells. Therefore, the development of new chemotherapeutic agents that are not substrates of these transporters is important. We have recently demonstrated that some members of a novel series of pyrrolo-1,5-benzoxazepine (PBOX) compounds are microtubule-depolymerising agents that potently induce apoptosis in several cancer cell lines and impair growth of mouse breast tumours. The aim of this current study was to establish whether PBOXs were capable of inducing apoptosis in cancer cells expressing either P-glycoprotein or breast cancer resistance protein (BCRP), two of the main ABC transporters associated with MDR.

METHODS: We performed in vitro studies to assess the effects of PBOXs on cell proliferation, cell cycle and apoptosis in human cancer cell lines and their drug-resistant substrains expressing either P-glycoprotein or BCRP. In addition, we performed a preliminary molecular docking study to examine interactions between PBOXs and P-glycoprotein.

RESULTS: We established that three representative PBOXs, PBOX-6, -15 and -16 were capable of inducing apoptosis in drug-resistant HL60-MDR1 cells (expressing P-glycoprotein) and HL60-ABCG2 cells (expressing BCRP) with similar potencies as in parental human promyelocytic leukaemia HL60 cells. Likewise, resistance to PBOX-6 and -16 was not evident in P-glycoprotein-expressing A2780-ADR cells in comparison with parent human ovarian carcinoma A2780 cells. Finally, we deduced by molecular docking that PBOX-6 is not likely to form favourable interactions with the substrate binding site of P-glycoprotein.

CONCLUSION: Our results suggest that pro-apoptotic PBOX compounds may be potential candidates for the treatment of P-glycoprotein- or BCRP-associated MDR cancers.