Feed balances for ruminant livestock: gridded estimates for data-constrained regions.

Demand for animal-source foods and livestock feed are forecast to increase across sub-Saharan Africa. In this context, there is a need to estimate the availability of livestock feed to support decision-making at local, sub-national and national levels. In this study, we assess feed balances for ruminant livestock in Ethiopia and Burkina Faso. Feed availability was estimated using remotely sensed products and detailed feed composition data. Feed requirements were estimated for maintenance, growth, lactation, gestation and locomotion using a data-intensive model. Biomass available as animal feed was estimated to be 8.6 tonnes of DM per hectare in the Ethiopian highlands and midlands, 3.2 tonnes DM per hectare in the Ethiopian lowlands, 2.9 tonnes DM per hectare in Burkina Faso's Sudanian agro-ecological zone and 1.0 tonne DM per hectare in the Sahel. The energy requirements of lactating cows were estimated to be 62.1 Megajoules (MJs) per animal per day in the Ethiopian highlands and midlands, 62.7 MJ in the Ethiopian lowlands, 88.5 MJ in Burkina Faso's Sudanian agro-ecological zone and 53.1 MJ per animal per day in the Sahel. Feed scarcity hotspots are most prominently located in the Ethiopian highlands and the Sahelian agro-ecological zone of Burkina Faso. Demand-side policy and investment initiatives can address hotspots by influencing herd sizes, nutritional requirements and herd mobility. Supply-side policy and investment initiatives can secure existing feed resources, develop new sources of feed and incentivise trade in feed resources. Improving feed balances will be of value to decision-makers with the aims of optimising livestock productivity, minimising exposure to climatic shocks and minimising greenhouse gas emission intensity.

Impacts of climate change on the livestock food supply chain; a review of the evidence.

The potential impacts of climate change on current livestock systems worldwide are a major concern, and yet the topic is covered to a limited extent in global reports such as the ones produced by the Intergovernmental Panel on Climate Change. In this article, we review the risk of climate-related impacts along the land-based livestock food supply chain. Although a quantification of the net impacts of climate change on the livestock sector is beyond the reach of our current understanding, there is strong evidence that there will be impacts throughout the supply chain, from farm production to processing operations, storage, transport, retailing and human consumption. The risks of climate-related impacts are highly context-specific but expected to be higher in environments that are already hot and have limited socio-economic and institutional resources for adaptation. Large uncertainties remain as to climate futures and the exposure and responses of the interlinked human and natural systems to climatic changes over time. Consequently, adaptation choices will need to account for a wide range of possible futures, including those with low probability but large consequences.

Assessment of the reliability and validity of a novel point-of-care fibrinogen (F-Point) device against an industry standard at fibrinogen levels >2 g/L in non-haemorrhage scenarios.

INTRODUCTION: A diagnostic accuracy study assessing the reliability and validity of a novel plasma fibrinogen point-of-care (F-Point) device compared with the von Clauss method of assay. METHODS: Forty-one women presenting for elective caesarean delivery and 43 non-pregnant female patients presenting for elective gynaecological surgery were recruited to assess agreement at normal fibrinogen levels (elective gynaecological cohort) and high fibrinogen levels (elective caesarean section cohort). Validity was assessed by comparing the F-Point results with the gold standard of von Clauss fibrinogen assay performed on the ACL Top 500. Reliability (test-retest) and validity were assessed using the intraclass correlation to control for operator variance (two-way random absolute agreement method), presented as intra class correlation coefficients (ICCs) and 95% confidence interval, and Bland-Altman analysis, presented as mean bias and 95% limits of agreement and coefficient of variation (COV). RESULTS: The results demonstrated a high test-retest reliability demonstrated in the paired F-Point measurements with an intraclass correlation coefficient (ICC) of 0.95, a bias of 0 (-00.69 to 0.69) and a COV of 9%. Similarly, there was acceptable agreement demonstrated between F-Point and von Clauss assay with an ICC of 0.91, a bias of -0.1 (-0.96 to 0.75) and a COV of 11%. CONCLUSIONS: Our novel plasma fibrinogen point-of-care device has been shown to be reliable and valid when testing fibrinogen levels as low as 2 g/L. Future studies investigating the correlation at lower fibrinogen levels, for example during haemorrhage and in patients with coagulopathies, are required.

Pediatric endocrine society survey of diabetes practices in the United States: What is the current state?

BACKGROUND: The Practice Management Committee (PMC) of the Pediatric Endocrine Society (PES) conducted a survey of its membership in February/March, 2016 to assess the current state of pediatric diabetes care delivery across multiple practice types in the United States. METHODS: The PES distributed an anonymous electronic survey (Survey Monkey) via email to its membership and requested that only one survey be completed for each practice. RESULTS: Ninety-three unique entries from the US were entered into analysis. Care is predominantly delivered by multidisciplinary teams, based at academic institutions (65.6%), with >85% of the provider types being physicians. Each 1.0 full time equivalent certified diabetes educators serves on average 367 diabetic youth. Fee-for-service remains the standard method of reimbursement with 57% of practices reporting financial loss. Survey respondents identified under-reimbursement as a major barrier to improving patient outcomes and lack of behavioral health (BH) providers as a key gap in services provided. CONCLUSIONS: Our survey reveals wide variation in all aspects of pediatric diabetes care delivery in the United States. Pediatric Endocrinologists responding to the survey identified a lack of resources and the current fee for service payment model as a major impediment to practice and the lack of integrated BH staff as a key gap in service. The respondents strongly support its organizations' involvement in the dissemination of standards for care delivery and advocacy for a national payment model aligned with chronic diabetes care in the context of our emerging value-based healthcare system.

Polymer encapsulation of anticancer silver-N-heterocyclic carbene complexes.

Amphiphilic block copolymers have been developed for the encapsulation of organometallic drugs. silver-N-heterocyclic carbene complexes have shown significant promise as anticancer and antibacterial compounds, and have been studied as the payload in these carriers. Simple modification of the N-heterocyclic carbene ligand structure enables solubility properties and interaction with the polymer to be tuned.

Extended follow-up and impact of high-risk prognostic factors from the phase 3 RESONATE study in patients with previously treated CLL/SLL.

In the phase 3 RESONATE study, ibrutinib demonstrated superior progression-free survival (PFS), overall survival (OS) and overall response rate (ORR) compared with ofatumumab in relapsed/refractory CLL patients with high-risk prognostic factors. We report updated results from RESONATE in these traditionally chemotherapy resistant high-risk genomic subgroups at a median follow-up of 19 months. Mutations were detected by Foundation One Heme Panel. Baseline mutations in the ibrutinib arm included TP53 (51%), SF3B1 (31%), NOTCH1 (28%), ATM (19%) and BIRC3 (14%). Median PFS was not reached, with 74% of patients randomized to ibrutinib alive and progression-free at 24 months. The improved efficacy of ibrutinib vs ofatumumab continues in all prognostic subgroups including del17p and del11q. No significant difference within the ibrutinib arm was observed for PFS across most genomic subtypes, although a subset carrying both TP53 mutation and del17p had reduced PFS compared with patients with neither abnormality. Reduced PFS or OS was not evident in patients with only del17p. PFS was significantly better for ibrutinib-treated patients in second-line vs later lines of therapy. The robust clinical activity of ibrutinib continues to show ongoing efficacy and acceptable safety consistent with prior reports, independent of various known high-risk mutations.

Comparison of bioreactance and echocardiographic non-invasive cardiac output monitoring and myocardial function assessment in primagravida women.

BACKGROUND.: Non-invasive cardiac output monitoring (NICOM) using bioreactance (BRT) in pregnancy is gaining interest but lacks validation. We compared simultaneous cardiac output (CO) measurements obtained using the NICOM ® (BRT-CO) and echocardiography (echo-CO), and assessed the relationship between maternal characteristics and myocardial performance. METHODS.: Paired stroke volume (SV) and CO readings were obtained using NICOM ® and echocardiography, in a group of healthy nulliparous women throughout a 15 min period. Agreement between NICOM ® and echocardiography was assessed using Bland-Altman analysis and the intraclass correlation coefficient (ICC). Left ventricular (LV) function was assessed using systolic strain and tissue Doppler velocities (S', E', and A' waves). RESULTS.: Thirty-five women with a median [interquartile range] age, weight, and gestation of 29 [26-34] yr, 71 [64-79] kg, and 28 [21-29] weeks, respectively, were enrolled. There was good agreement between NICOM ® -measured and echocardiographically measured SV [mean bias 6 ml (limits of agreement -18 to 29); ICC 0.8 (95% confidence interval 0.6-0.9), P <0.001] and CO [mean bias 0.2 litres (limits of agreement -1.3-1.7); ICC 0.8 (95% confidence interval 0.7-0.9), P <0.001; mean percentage error ±26%; coefficient of error (precision)=3.4%]. The mean ( sd ) LV S' was 9.7 (2.3) cm s -1 . The mean ( sd ) LV strain was -18.6 (2.6)%. There was a negative relationship between BMI and LV diastolic function measured using the E':A' ratio ( r = -0.51, P <0.01). CONCLUSIONS.: Stroke volume and CO measurements obtained using NICOM ® were comparable to those obtained using echocardiography, with acceptable limits of agreement. Increased maternal BMI negatively impacts LV diastolic function measured using tissue Doppler imaging.

Climate change and pastoralism: impacts, consequences and adaptation.

The authors discuss the main climate change impacts on pastoralist societies, including those on rangelands, livestock and other natural resources, and their extended repercussions on food security, incomes and vulnerability. The impacts of climate change on the rangelands of the globe and on the vulnerability of the people who inhabit them will be severe and diverse, and will require multiple, simultaneous responses. In higher latitudes, the removal of temperature constraints might increase pasture production and livestock productivity, but in tropical arid lands, the impacts are highly location specific, but mostly negative. The authors outline several adaptation options, ranging from implementing new technical practices and diversifying income sources to finding institutional support and introducing new market mechanisms, all of which are pivotal for enhancing the capacity of pastoralists to adapt to climate variability and change. Due to the dynamism of all the changes affecting pastoral societies, strategies that lock pastoral societies into specified development pathways could be maladaptive. Flexible and evolving combinations of practices and policies are the key to successful pastoral adaptation.

Les auteurs examinent les principaux effets du changement climatique sur les sociétés pastorales, en particulier ceux qui affectent les prairies, le bétail et d'autres ressources naturelles ainsi que les répercussions durables sur la sécurité alimentaire, sur les revenus et sur la vulnérabilité des populations. Le changement climatique va profondément et diversement affecter les prairies de la planète et le degré de vulnérabilité des personnes qui y vivent, ce qui imposera de déployer des réponses multiples et simultanées. Si dans les latitudes plus élevées, la suppression de certaines contraintes liées aux températures permet d'augmenter la production d'herbage et d'accroître la productivité du bétail, dans les terres arides tropicales les effets du climat, très spécifiques selon les endroits, sont majoritairement négatifs. Les diverses solutions adaptatives mises en avant par les auteurs, depuis la mise en oeuvre de nouvelles techniques et la diversification des sources de revenus jusqu'à la recherche de soutiens institutionnels et la création de nouveaux mécanismes de marché, sont toutes déterminantes pour améliorer la capacité des pasteurs à s'adapter à la variabilité et au changement climatiques. En raison du caractère dynamique des changements affectant les sociétés pastorales, les stratégies consistant à confiner ces sociétés dans des tracés spécifiques de développement risquent de s'avérer contreproductives en termes d'adaptation. Un assortiment souple et évolutif de pratiques et de politiques est la clé d'une adaptation pastorale réussie.

Los autores examinan los principales efectos del cambio climático sobre las sociedades pastorales, en particular los que afectan a las tierras de pasto, el ganado y otros recursos naturales, así como sus repercusiones más indirectas sobre la seguridad alimentaria, los ingresos y la vulnerabilidad. El cambio climático traerá consigo diversos efectos de gravedad que influirán en los pastizales del planeta y la vulnerabilidad de quienes viven de ellos, efectos que exigirán múltiples respuestas simultáneas. En altas latitudes, la desaparición de las limitaciones ligadas a la temperatura podría deparar una mayor producción de los pastizales y con ello una mayor productividad del ganado, pero en las tierras áridas tropicales los efectos dependerán en gran medida de las condiciones de cada localidad y serán mayormente negativos. Los autores destacan varias posibilidades de adaptación, desde la aplicación de nuevos procedimientos técnicos y la diversificación de las fuentes de ingresos hasta la obtención de apoyo institucional, pasando por la instauración de nuevos mecanismos de mercado, todas ellas soluciones cruciales para dotar a las sociedades de pastores de mayor capacidad de adaptación a la variabilidad y la evolución del clima. Teniendo en cuenta el dinamismo de cuantos cambios afectan a las sociedades pastorales, toda estrategia que las encorsete en una u otra vía específica de desarrollo podría resultar inadaptada. La clave para una adaptación fructífera de esas sociedades estriba en combinaciones de prácticas y políticas que sean flexibles y evolucionen en el tiempo.

Cutaneous skeletal hypophosphatemia syndrome: clinical spectrum, natural history, and treatment.

Cutaneous skeletal hypophosphatemia syndrome (CSHS), caused by somatic RAS mutations, features excess fibroblast growth factor-23 (FGF23) and skeletal dysplasia. Records from 56 individuals were reviewed and demonstrated fractures, scoliosis, and non-congenital hypophosphatemia that in some cases were resolved. Phosphate and calcitriol, but not skin lesion removal, were effective at controlling hypophosphatemia. No skeletal malignancies were found. PURPOSE: CSHS is a disorder defined by the association of epidermal and/or melanocytic nevi, a mosaic skeletal dysplasia, and an FGF23-mediated hypophosphatemia. To date, somatic RAS mutations have been identified in all patients whose affected tissue has undergone DNA sequencing. However, the clinical spectrum and treatment are poorly defined in CSHS. The purpose of this study is to determine the spectrum of the phenotype, natural history of the disease, and response to treatment of hypophosphatemia. METHODS: Five CSHS subjects underwent prospective data collection at clinical research centers. A review of the literature identified 45 reports that included a total of 51 additional patients, in whom the findings were compatible with CSHS. Data on nevi subtypes, bone histology, mineral and skeletal disorders, abnormalities in other tissues, and response to treatment of hypophosphatemia were analyzed. RESULTS: Fractures, limb deformities, and scoliosis affected most CSHS subjects. Hypophosphatemia was not present at birth. Histology revealed severe osteomalacia but no other abnormalities. Skeletal dysplasia was reported in all anatomical compartments, though less frequently in the spine; there was no clear correlation between the location of nevi and the skeletal lesions. Phosphate and calcitriol supplementation was the most effective therapy for rickets. Convincing data that nevi removal improved blood phosphate levels was lacking. An age-dependent improvement in mineral abnormalities was observed. A spectrum of extra-osseous/extra-cutaneous manifestations that included both benign and malignant neoplasms was present in many subjects, though osteosarcoma remains unreported. CONCLUSION: An understanding of the spectrum, natural history, and efficacy of treatment of hypophosphatemia in CSHS may improve the care of these patients.

A four-year, open-label, multi-center, randomized, two-arm study of Genotropin® in patients with idiopathic short stature: comparison of an individualized, target-driven treatment regimen to standard dosing of Genotropin® - analysis of two-year data.

BACKGROUND: Several models have been developed to predict growth response to growth hormone (GH) based on auxological and biochemical parameters for children with non-GH-deficient, idiopathic short stature (ISS). OBJECTIVE: To demonstrate if an individualized, formula-based, target-driven GH regimen for children with ISS would lead to a height (Ht) gain to -1.3 SDS during the first 24 months of treatment of this 4-year study, with less variability than with standard weight-based dosing. METHODS: A 4-year, open-label, multi-center, randomized, two-arm study comparing formula-based dosing of Genotropin® GH from 0.18 to 0.7 mg/kg/week versus standard FDA-approved ISS dosing of Genotropin® (0.37 mg/kg/week). Subjects (n = 316, 89 females) were prepubertal, 3-14 years of age, bone age 3-10 years (m) and 3-9 years (f), naive to GH treatment, Ht SDS -3 to -2.25, Ht velocity <25th percentile for bone age, and peak GH >10 ng/ml. RESULTS: The majority (83%) of subjects had Ht SDS within the normal range by 2 years. All subjects displayed catch-up growth consistent with other studies of GH treatment of ISS. CONCLUSION: The formula-based therapy did not meet the primary endpoint achieving targeted gain with lower variability. No new safety concerns were found.

R-loops and nicks initiate DNA breakage and genome instability in non-growing Escherichia coli.

Double-stranded DNA ends, often from replication, drive genomic instability, yet their origin in non-replicating cells is unknown. Here we show that transcriptional RNA/DNA hybrids (R-loops) generate DNA ends that underlie stress-induced mutation and amplification. Depleting RNA/DNA hybrids with overproduced RNase HI reduces both genomic changes, indicating RNA/DNA hybrids as intermediates in both. An Mfd requirement and inhibition by translation implicate transcriptional R-loops. R-loops promote instability by generating DNA ends, shown by their dispensability when ends are provided by I-SceI endonuclease. Both R-loops and single-stranded endonuclease TraI are required for end formation, visualized as foci of a fluorescent end-binding protein. The data suggest that R-loops prime replication forks that collapse at single-stranded nicks, producing ends that instigate genomic instability. The results illuminate how DNA ends form in non-replicating cells, identify R-loops as the earliest known mutation/amplification intermediate, and suggest that genomic instability during stress could be targeted to transcribed regions, accelerating adaptation.

Gross chromosomal rearrangement mediated by DNA replication in stressed cells: evidence from Escherichia coli.

Gross chromosomal rearrangements (GCRs), or changes in chromosome structure, play central roles in evolution and are central to cancer formation and progression. GCRs underlie copy number variation (CNV), and therefore genomic disorders that stem from CNV. We study amplification in Escherichia coli as a model system to understand mechanisms and circumstances of GCR formation. Here, we summarize observations that led us to postulate that GCR occurs by a replicative mechanism as part of activated stress responses. We report that we do not find RecA to be downregulated by stress on a population basis and that constitutive expression of RecA does not inhibit amplification, as would be expected if downregulation of RecA made cells permissive for nonhomologous recombination. Strains deleted for the genes for three proteins that inhibit RecA activity, psiB, dinI, and recX, all show unaltered amplification, suggesting that if they do downregulate RecA indirectly, this activity does not promote amplification.

Timing and magnitude of C partitioning through a young loblolly pine (Pinus taeda L.) stand using 13C labeling and shade treatments.

The dynamics of rapid changes in carbon (C) partitioning within forest ecosystems are not well understood, which limits improvement of mechanistic models of C cycling. Our objective was to inform model processes by describing relationships between C partitioning and accessible environmental or physiological measurements, with a special emphasis on short-term C flux through a forest ecosystem. We exposed eight 7-year-old loblolly pine (Pinus taeda L.) trees to air enriched with (13)CO(2) and then implemented adjacent light shade (LS) and heavy shade (HS) treatments in order to manipulate C uptake and flux. The impacts of shading on photosynthesis, plant water potential, sap flow, basal area growth, root growth and soil CO(2) efflux rate (CER) were assessed for each tree over a 3-week period. The progression of the (13)C label was concurrently tracked from the atmosphere through foliage, phloem, roots and surface soil CO(2) efflux. The HS treatment significantly reduced C uptake, sap flow, stem growth and fine root standing crop, and resulted in greater residual soil water content to 1 m depth. Soil CER was strongly correlated with sap flow on the previous day, but not the current day, with no apparent treatment effect on the relationship. Although there were apparent reductions in new C flux belowground, the HS treatment did not noticeably reduce the magnitude of belowground autotrophic and heterotrophic respiration based on surface soil CER, which was overwhelmingly driven by soil temperature and moisture. The (13)C label was immediately detected in foliage on label day (half-life = 0.5 day), progressed through phloem by Day 2 (half-life = 4.7 days), roots by Days 2-4, and subsequently was evident as respiratory release from soil which peaked between Days 3 and 6. The δ(13)C of soil CO(2) efflux was strongly correlated with phloem δ(13)C on the previous day, or 2 days earlier. While the (13)C label was readily tracked through the ecosystem, the fate of root C through respiratory, mycorrhizal or exudative release pathways was not assessed. These data detail the timing and relative magnitude of C flux through various components of a young pine stand in relation to environmental conditions.

Global chromosomal structural instability in a subpopulation of starving Escherichia coli cells.

Copy-number variations (CNVs) constitute very common differences between individual humans and possibly all genomes and may therefore be important fuel for evolution, yet how they form remains elusive. In starving Escherichia coli, gene amplification is induced by stress, controlled by the general stress response. Amplification has been detected only encompassing genes that confer a growth advantage when amplified. We studied the structure of stress-induced gene amplification in starving cells in the Lac assay in Escherichia coli by array comparative genomic hybridization (aCGH), with polymerase chain reaction (pcr) and DNA sequencing to establish the structures generated. About 10% of 300 amplified isolates carried other chromosomal structural change in addition to amplification. Most of these were inversions and duplications associated with the amplification event. This complexity supports a mechanism similar to that seen in human non-recurrent copy number variants. We interpret these complex events in terms of repeated template switching during DNA replication. Importantly, we found a significant occurrence (6 out of 300) of chromosomal structural changes that were apparently not involved in the amplification event. These secondary changes were absent from 240 samples derived from starved cells not carrying amplification, suggesting that amplification happens in a differentiated subpopulation of stressed cells licensed for global chromosomal structural change and genomic instability. These data imply that chromosomal structural changes occur in bursts or showers of instability that may have the potential to drive rapid evolution.