Limited Growth Potential Research Articles

Morphological responses of three contrasting Soybean (Glycine max (L.) Merrill) genotypes under different levels of salinity stress in the coastal region of Bangladesh

Soil salinity, a global environmental issue, inhibits plant development and production. Soybean is an economically important legume crop whose yield and quality are highly affected by excessive levels of salt in the root zone. A factorial experiment was conducted in a net house from October 2019 to January 2020 to evaluate the performance of three distinct soybean genotypes under varying levels of salinity stress. The experiment followed a completely randomized design (CRD) with three replications. Three soybean cultivars, namely BINA Soybean 1, BINA Soybean 2, and BINA Soybean 4 were used in this experiment. The soil salinity treatments were 0 mM NaCl, 50 mM NaCl, 100 mM NaCl, 150 mM NaCl, and 200 mM NaCl. The electrical conductivity (EC) of the soil sample was 0.91dS/m. Six seeds were sown 3 cm deep in each pot. A total of 45 pots were used in this experiment. The performance of each variety was evaluated based on its germination percentage, time of germination, no. of branches/plant, no. of leaves/plant, no. of flowers/plant, plant height (cm), no. of pods/plant, pod length (cm), seeds/pod, and root length (cm). Based on the results obtained from this research trial, it can be inferred that the BINA Soybean 2 variety along with 0 mM NaCl, 50 mM NaCl, and 100 mM NaCl treatments exhibited superior performance in all parameters compared to the other varieties. This study provides clear evidence that the soybean, particularly the BINA Soybean 2 variety, holds significant promise as a crop suitable for coastal regions. Furthermore, it suggests that the cultivation of soybeans in such areas could potentially enhance agricultural productivity, particularly in the presence of mild saline conditions. Nevertheless, it exhibits limited growth potential in environments with elevated salinity levels.

Post-Pandemic Home-Based Work in Cities of the South Lessons from Enugu, Nigeria

Income-generating activities in residential zones known as Home-Based Enterprises (HBEs) are becoming more prevalent as a result of the COVID-19 pandemic. The informal sector, including HBEs, started expanding in cities of the Global South in the 1980s during the Structural Adjustment Programme and has engendered debates among practitioners and researchers. The International Labour Organization Home Work Convention, C177 of 1996, and the inclusion of home work in national accounting because of its contribution to Gross Domestic Product have emboldened researchers to argue for a supportive policy framework. Yet, this phenomenon is still opposed by contemporary planning practices in many Global South cities. The lockdown during the pandemic which aff ected every aspect of life across the world revealed the indispensability of home-based enterprises: 'work' that had to be kept functional was done from home. Will the implications of lockdown and post-pandemic home-based work lead to a paradigm shift in the Global South from the rigid colonial planning standards to eff ective and dynamic planning standards that are based on contemporary urban realities? The aim of this study is, therefore, to examine the implications of post-pandemic home-based enterprise for the built environment in Global South cities using Enugu, Nigeria as a case study. The mixed research design was adopted for the study, while data were collected through questionnaires and in-depth interviews. Stratified random sampling was employed to select three (one low, medium, and high density) from the existing thirty-three formal neighbourhoods in the study city – Enugu. Systematic sampling was adopted to select the sample size among the residents and the professionals were selected purposively. The result of the principal component analysis reveals that there are six major impacts of HBEs on the built environment in Enugu, namely: entrepreneurship skills; pressure on infrastructure; improved living standards; discrimination; in fluence on work–life balance; and limited growth potential. Major lessons from the study include:adaptation of innovative urban planning; enhancement of local economic development; gender and policy issues.This research is signi ficant as it will contribute to the literature on COVID-19 in the Global South and connect the post-COVID-19 recovery experience from a core Global South city to possible, effective actions that can mitigate future challenges in comparable cities and contexts.

The quest for the holy grail: overcoming challenges in expanding human hematopoietic stem cells for clinical use.

Hematopoietic stem cell (HSC) transplantation has been the golden standard for many hematological disorders. However, the number of HSCs obtained from several sources, including umbilical cord blood (UCB), often is insufficient for transplantation. For decades, maintaining or even expanding HSCs for therapeutic purposes has been a "holy grail" in stem cell biology. Different methods have been proposed to improve the efficiency of cell expansion and enhance homing potential such as co-culture with stromal cells or treatment with specific agents. Recent progress has shown that this is starting to become feasible using serum-free and well-defined media. Some of these protocols to expand HSCs along with genetic modification have been successfully applied in clinical trials and some others are studied in preclinical and clinical studies. However, the main challenges regarding ex vivo expansion of HSCs such as limited growth potential and tendency to differentiate in culture still need improvements. Understanding the biology of blood stem cells, their niche and signaling pathways has provided possibilities to regulate cell fate decisions and manipulate cells to optimize expansion of HSCs in vitro. Here, we review the plethora of HSC expansion protocols that have been proposed and indicate the current state of the art for their clinical application.

Established Immortalized Cavernous Endothelial Cells Improve Erectile Dysfunction in Rats with Cavernous Nerve Injury.

The main cause of erectile dysfunction (ED) is the damage in penile cavernous endothelial cells (EC). Murine primary ECs have a limited growth potential, and the easy availability of murine ECs will facilitate the study of cavernous endothelial dysfunction in rats. This study was performed to establish immortalized rat penile cavernous ECs (rEC) and investigate how they could repair erectile dysfunction in rats with cavernous nerve injury (CNI). rEC was isolated enzymatically by collagenase digestion and were cultured. An amphotropic replication-incompetent retroviral vector encoding v-myc oncogene was used to transfect rEC for immortalization (vREC). Morphological and immunohistochemical properties of vREC were examined. Eight-week-old male Sprague-Dawley rats were divided into three groups of five rats each, including group 1 = sham operation, group 2 = bilateral CN injury, group 3 = vREC (1 × 106 cells) treatment after CNI. Erectile response was assessed at 2, 4 weeks after transplantation of vREC., Penile tissue were harvested at 4 weeks after transplantation and immune-histochemical examination was performed. vREC showed the expression of CD31, vWF, cell type-specific markers for EC by RT-PCR and flowcytometry. At 2, 4 weeks after transplantation, rats with CNI had significantly lower erectile function than control group (p < 0.05). The group transplanted with vREC showed higher erectile function than the group without vRECs (p < 0.05). vREC was established and repaired erectile dysfunction in rats with CNI. This cell line may be useful for studying mechanisms and drug screening of erectile dysfunction of rats.

Intraoral Sialadenoma Papilliferum: A Comprehensive Review of the Literature with Emphasis on Clinical and Histopathological Diagnostic Features

Background. Sialadenoma papilliferum (SP) is a rare benign epithelial tumor of salivary gland origin, its diagnosis being potentially challenging. It was first described by Abrams and Finck in 1969 as an analog of the cutaneous syringocystadenoma papilliferum. The aim of this comprehensive review is to highlight the clinical and histopathological diagnostic aspects of intraoral SP, analyzing cases previously described and reporting new cases. Methods. Medline, Scopus, and Web of Science were searched up to February 2022, using as entry term “sialadenoma papilliferum”. No time limits were applied and only studies in English were taken into account. Only cases involving the mouth were included. Conference proceedings, personal communications, and letters to the editor were excluded. Results. In total, 42 out of 234 articles fulfilled the inclusion criteria, with 64 cases reported. Mean age of patients with SP was 57.2 years, with a higher prevalence among males. The most affected site was the palate, particularly the hard palate. Four cases with uncertain malignant features have been reported. While clinical manifestations of SP are rather unspecific (e.g., submucosal swelling with ulceration), histopathological and immunohistochemical features are quite peculiar, SP have a limited growth potential, leading to conservative excision as treatment of choice. Conclusions. SP, though rare, should be taken into consideration in the differential diagnosis of intraoral swellings, particularly those located on the palate.

Case series of Adenomatoid Odontogenic Tumors: Clinical, Radiographic, and Histologic Features

<h3>Objective</h3> We present a case series of adenomatoid odontogenic tumor (AOT), a benign odontogenic tumor from a large biopsy service. AOT has a limited growth potential and is often seen in children and young adults, between the ages of 10-19 years. AOT has uncertain pathogenesis and studies suggest enamel organ, reduced enamel epithelium, and rests of Malassez as potential sources. Clinically, AOT's are asymptomatic and identified upon routine radio- graphic examination. <h3>Methods</h3> Information was collected from the University of Florida Oral Pathology Biopsy Service archives (1994-2019). The clinical and demographic data along with any accompanying radiographic images and original slides were evaluated. <h3>Results</h3> A total of 26 cases of AOT were identified, with a mean age of 22.3 years (range: 12-67). A slight female predilection was noted (57.7%, n=15). Most cases presented in the anterior region of the jaw (73%, n=19) and a slight maxillary predilection was observed (61.5%, 16 cases). Most patients were aged under 20 (69.2%, n=18). Clinical impression included dentigerous cyst, lateral periodontal cyst, and odontogenic keratocyst (57.7%, n=15). Radiographs were available for six cases and all presented as a unilocular radiolucency. The histologic diagnosis was consistent with AOT in 24 cases and peripheral AOT in two cases.One case had a fo- cal area of CEOT that tested positive with a Congo Red stain. <h3>Conclusion</h3> In almost all cases within the study the clinical impression of AOT was not rendered. This implied that AOT is rarely considered in the differential of such lesions. In addition, while most patients were children or young adults, there were a few outliers above thirty (19.2%, n=5). This may suggest that AOT is diagnosed late in some cases due to its benign nature. Clinicians should be sentient of this lesion as the treatment and prognosis differs from other odontogenic cysts and tumors.

Mitsubishi restructures

Following in the footsteps of other major petrochemical firms, such as DSM and Bayer, that have shed commodity chemical businesses, Mitsubishi Chemical Holdings says it plans to carve out and divest its petrochemical and coal-chemical units by its 2023 fiscal year. The petrochemical business had sales during the last fiscal year of $3.8 billion, about 13% of Mitsubishi’s total. It makes olefins and polyolefins. The coal business, which makes coke, carbon black, and synthetic rubber, had sales of $1.0 billion. Mitsubishi says the businesses face both limited growth potential and difficulties as Japan shifts toward carbon neutrality. The company says electronics and health care will be its strategic focus, though it also wants to improve the competitiveness of businesses such as methyl methacrylate and industrial gases. The carve-out plan is the first major initiative at Mitsubishi under CEO Jean-Marc Gilson, who joined the company in April after a career at

Wedge-less oblique supracondylar femoral osteotomy and casting for genu valgum in older children and young adults

BackgroundGenu valgum is one of the commonest deformities seen by the orthopaedicians. The most common cause is idiopathic but genu valgum secondary to nutritional deficiency is also fairly common in developing and third world countries. Supracondylar osteotomy and internal fixation with plate and screws, is the treatment of choice in older children and young adults, which is costly, requires a wide exposure, a second surgery for implant removal and risk of infection is more. This study was undertaken to measure the outcome of simple oblique percutaneous wedge-less metaphyseal supracondylar osteotomy of the distal femur and casting in older children and adolescents with Genu Valgum in a small centre catering mostly to patients from middle and low income households. Patients and methodsPatients aged between 12 and 22 years with genu valgum deformity with a tibiofemoral angle ≥15°, and an intermalleolar distance of more than 7 cm in unilateral and more than 10 cm in bilateral cases, who are not amenable to be treated with guided growth techniques, were included. Patients having knee instability, restriction of knee range of motion, genu recurvatum, tibial deformity component, open physis, were excluded from the study. The correction was undertaken by a simple supracondylar wedge-less metaphyseal short oblique osteotomy of the distal femur followed by immobilization with a long leg plaster of Paris cast. Functional outcome was assessed using Böstman et al. score. Results46 limbs in 29 patients with a mean age of 14.5 years were operated. The mean follow-up of patients was 6 months. The preoperative radiological tibiofemoral angle (TFA) had a mean value of 19.89° which improved to a mean of 5.31° postoperatively. Intermalleolar distance (IMD) improved from a mean of 13.81 cm to 3.15 cm post-correction. Mean Lateral distal femoral angle (LDFA) improved from 77.11° to 87.20°. Knee score was excellent in all patients at 3 months and 6 months post intervention. There were no serious complications except superficial plaster sores in 4 patients, which healed uneventfully and temporary restriction of knee range of motion in 5 patients. All patients achieved a full range of knee motion after physical therapy. ConclusionSupracondylar wedge-less short oblique metaphyseal distal femoral osteotomy and immobilization with plaster of Paris cast is a simple, cheap, safe & viable option for the correction of genu valgum deformity originating from distal femur, with minimal complications in older children and adolescents with limited growth potential, especially in low income countries and small centres.

Accumulation of Toxic Advanced Glycation End-Products Induces Cytotoxicity and Inflammation in Hepatocyte-Like Cells Differentiated from Human Induced Pluripotent Stem Cells.

Nonalcoholic steatohepatitis (NASH), the aggressive form of the most common chronic liver disease nonalcoholic fatty liver disease, is characterized by inflammation and damage in the liver. Although hepatocyte injury and cell death have been identified as cardinal pathological features of NASH, its pathogenesis has not yet been elucidated in detail. Immortalized cell lines and primary cultured cells have been used as in vitro models of NASH. However, these cells have several disadvantages, such as specialized characteristics by immortalization or limited growth potential. To overcome these difficulties and develop a strategy to analyze the pathology of NASH, we employed hepatocyte-like cells differentiated from human induced pluripotent stem cells (hiPSC-HLCs) as an in vitro model of NASH to clarify the intracellular effects of glyceraldehyde-derived advanced glycation end-products (AGEs), also named toxic AGEs (TAGE). The viability of hiPSC-HLCs decreased with the accumulation of TAGE in the cells, which was consistent with previous findings on human hepatocellular carcinoma cells and human primary cultured hepatocytes. In addition, the TAGE accumulation up-regulated the expression of inflammation-related genes (interleukin 6, interleukin 8, and monocyte chemoattractant protein-1) in hiPSC-HLCs. These results indicated that the accumulation of TAGE induced hiPSC-HLC cytotoxicity and inflammation, which are features of the pathology of NASH. Therefore, we suggest the use of hiPSC-HLCs as an important strategy for analyses of the pathology of NASH.

Iceland’s Economic Growth Prospects in the Post-Covid-19 Period

Due to the global coronavirus pandemic Iceland is facing the largest economic crisis for half a century. But after the pandemic is over, the economy is expected to quickly recover and continue its further growth. In this article, the author intends to explore how well these expectations are justified and which industry sectors could contribute to Iceland’s economic growth. The analysis shows that the country’s current key export sectors (tourism, seafood production and aluminum industry) have a limited growth potential, mainly related to the ongoing development of aquaculture. The paper also considers key economic projects, linked to utilization of Iceland’s resource and innovative potential. The abundance of cheap renewable energy enables the country to develop new energy-intensive projects (silicon smelters and data centers), as well as to consider the possibility to directly transmit electricity to the UK (project IceLink). These initiatives could significantly contribute to the future economic growth, although the Icelandic energy industry is not limitless. However, the biggest economic growth is expected in innovative industry sectors. A number of projects in bioengineering, biomedicine, pharmacology, and high-tech equipment production have been started in Iceland. In the longterm perspective, their potential profits could exceed the ones of the resource sector of the country’s economy.

Innovative Rural Entrepreneurship in Chile

Successful policies seeking to promote rural entrepreneurship require a conceptual model consistent with the features of rural spaces and free of stereotypes of entrepreneurship as being only technologically sophisticated. The objective of this essay is, first, to argue that rural areas can be fertile ground for entrepreneurial activities in middle-income countries such as Chile and, second, to discuss policy options to achieve the goal of encouraging a more innovative entrepreneurship in rural areas. The scientific literature on entrepreneurship and the definitions, types and roles of entrepreneurship in development are reviewed. The literature on the location of entrepreneurship is summarized to understand the drivers of observed territorial differences in entrepreneurial activity. One conclusion is that rural areas face a (seemingly) adverse economic geography for entrepreneurship, although there is a recent tendency for amenities-led growth. We then present the geography of rural entrepreneurship in Chile. Contrary to conventional wisdom, the rates of entrepreneurship in Chilean rural areas are high, although presumably of a limited growth potential under current conditions. Nevertheless, this entrepreneurial base provides a stock of knowledge from which a greater sophistication could be reached, and we discuss potential policy approaches to stimulate more innovative rural entrepreneurship. In the case of Chile, available policy options are coherent with the recently enacted National Rural Development Policy. A systemic, amenity-based approach gives middle-income countries opportunities for the development of more innovative rural entrepreneurship through territorial policies that provide local public goods and improve living conditions.

Free Non-vascularized Toe Phalangeal Transfers in Symbrachydactyly: Outcome Analysis

AbstractIntroduction Free nonvascularized toe phalangeal transfer is an established surgical option for the reconstruction of hypoplastic digits. The purpose of the present study was to evaluate our experience with this procedure and to assess bone growth and digit function as well foot morbidity.Material and Methods We retrospectively evaluated the clinical records for all children with symbrachydactyly submitted to free nonvascularized toe phalangeal transfer between 2002 and 2017. A total of 8 patients were included. We summoned the patients to an appointment to clinically assess the range of motion, the stability, and the alignment of the neo-joint. We radiographically measured the final length and the expected percentage of growth of the transferred phalanx. We also evaluated the foot for comorbidities.Results The mean age at the time of the first surgery was 19 months (range: 8–42 months). A total of 20 phalanges were harvested: 16 total proximal phalanges, 2 middle phalanges, 1 subtotal proximal phalanx, and 1 accessory thumb phalanx. The distal part of one proximal phalanx was trimmed because the skin pocket was too tight. Two patients underwent a secondary procedure to release the syndactyly. One transfer required revision surgery due to distal tip necrosis and exposition of the transferred phalanx. In the present series, the overall clinical and radiographic outcomes were compatible to those reported in other studies.Discussion The main limitation of the nonvascularized toe phalanx transfer is the preexisting soft tissue envelope of the finger and the limited growth potential of the transferred bone.Conclusion Irrespective of the amount of growth achieved in the transferred phalanx, the actual transfer and growth attained should not be viewed as the end result, but rather as a means of providing a stable and functional joint.

Development and validation of a nomogram prognostic model for esophageal cancer patients with oligometastases

Platinum-based chemotherapy is recommended as the standard treatment for metastatic esophageal cancer (EC) patients; however, the outcome is poor. Oligometastasis is less aggressive and has limited growth potential. However, the prognostic factors for EC patients with oligometastases was largely unknown. Thus, we intend to determine the prognostic factors, and develop and validate nomograms for prediction of survival for EC patients with oligometastases. In this study, characteristics of 273 oligometastatic EC patients were analyzed using univariate and multivariate Cox models to determine the independent prognostic factors for progression-free survival (PFS) and overall survival (OS). The result showed that history of alcohol consumption, longer tumor, no local radiotherapy for EC, and no local treatment for metastases were independent factors for PFS. Sex, esophageal fistula, number of metastatic organs, and local radiotherapy for EC were independent prognostic factors for OS. On the basis of Cox models, the respective nomogram for prediction of PFS and OS was established with the corrected concordance index of 0.739 and 0.696 after internal cross-validation. In conclusion, local treatment for metastases and local radiotherapy for EC were demonstrated to be beneficial for oligometastatic EC patients, and the validated nomograms are valuable in prognosis prediction and could guide individualized management for these patients.

Experience and Outcomes of Surgically Implanted Melody Valve in the Pulmonary Position

Multiple congenital cardiac malformations require pulmonary valve replacement and/or right ventricular outflow (RVOT) reconstruction. Pulmonary valve replacement remains challenging in children owing to the limited growth potential of prosthetic valves. We evaluated outcomes in patients undergoing surgical implantation of a Melody valve in the RVOT. Data were retrospectively collected for 23 patients undergoing surgical Melody valve implantation at Boston Children's Hospital between 2009 and 2019. We assessed postoperative valve function, reintervention rates, and mortality. Median age was 1.7 years (range, 2 months to 6 years); 12 patients were aged greater than 2 years (52%). Diagnosis was tetralogy of Fallot in 15 patients (65%); 15 had a prior RVOT operation (65%). The Melody valve was dilated before surgery to a median diameter of 14 mm (range, 10-20 mm). No patients had acute pulmonary regurgitation. One required transcatheter RVOT reintervention before discharge. Median follow-up was 3.7 years (range, 0.02-8.7 years) with moderate or greater pulmonary regurgitation in 2 patients. Catheter-based interventions (mean, 0.83 ± 1.07/patient) occurred at a median of 1 year (range, 16 days to 5.4 years) and included valve expansion for somatic growth (n= 10) and subsequent valve-in-valve replacement (n= 3). Three patients (13%) required surgical valve explant or replacement at a median of 1.0 year (range, 0.6-3.7 years) for Melody-specific indications. One-, 3-, and 5-year freedom from Melody-driven reoperation was 90%, 90%, and 83%, respectively. The Melody valve can be surgically implanted in the RVOT of young patients with acceptable early results. These valves can be successfully dilated through transcatheter reintervention to accommodate growth.

Effect Propensity: The Distribution of Switchers' Choices in the Reference State as a Determinant of the Direction of Effects on Choice

In a choice between two options, decision makers can often be divided into three segments: those who strongly prefer the first option, those who strongly prefer the second option, and those who might choose either option depending on the particular conditions (Switchers). In any reference state, such as the experimental control, most Switchers are likely to favor one of the two options. Thus, the limited growth potential of the option favored by Switchers in the reference state creates in the opposite direction, whereby any condition or manipulation applied to the reference state is more likely to increase the share of the other option. We test this proposition in a series of studies in the context of choices between safe and risky options and between lower-price/quality and higher-price/quality options. The results indicate that a large majority of conceptually unrelated manipulations tend to increase the choice share of risky and higher-price/quality options. This effect propensity can be reversed when the risky and higher-price/quality options are the status quo alternatives or asymmetrically dominating in the reference state. Alternative explanations for effect propensity are examined. We discuss the implications of effect propensity for the interpretation of research findings, the selection of controls, and theory tests.

Enhancing the Efficacy of Stem Cell Therapy with Glycosaminoglycans.

SummaryHuman mesenchymal stem cell (hMSC) therapy offers significant potential for osteochondral regeneration. Such applications require their ex vivo expansion in media frequently supplemented with fibroblast growth factor 2 (FGF2). Particular heparan sulfate (HS) fractions stabilize FGF2-FGF receptor complexes. We show that an FGF2-binding HS variant (HS8) accelerates the expansion of freshly isolated bone marrow hMSCs without compromising their naivety. Importantly, the repair of osteochondral defects in both rats and pigs is improved after treatment with HS8-supplemented hMSCs (MSCHS8), when assessed histologically, biomechanically, or by MRI. Thus, supplementing hMSC culture media with an HS variant that targets endogenously produced FGF2 allows the elimination of exogenous growth factors that may adversely affect their therapeutic potency.

Magnetically Controlled Growing Rods: The Experience of Mechanical Failure from a Single Center Consecutive Series of 28 Children with a Minimum Follow-up of 2 Years.

Study DesignRetrospective observational study of a continuous series of 28 children.PurposeTo determine the mechanical failure rate in our cohort of children treated with magnetically controlled growth rods (MCGRs).Overview of LiteraturePrevious studies report a MCGR mechanical failure rate of 0%–75%.MethodsAll patients with MCGR implantation between 2012 and 2015 were examined and followed up for a minimum of 2 years. A retrospective evaluation of contemporaneously documented clinical findings was conducted, and radiographs were retrospectively examined for mechanical failure. The external remote controller (ERC)-specified length achieved in the clinic was compared to the length measured on subsequent radiographs.ResultsFourteen mechanical failures were identified in 28 children (50%) across a total of 52 rods (24 pairs and four single constructs). Mechanical failures were due to: failure to lengthen under general anesthesia (seven children), actuator pin fracture (four), rod fracture (one), foundation screw failure (one), and ran out of rod length (one). Of the 14 mechanical failures, six were treated with final fusion operations (reflecting limited further growth potential), and eight patients were treated with the intention for further lengthening. We therefore consider these eight patients to represent the true incidence of mechanical failure in our cohort (29%). The difference between the ERC length and radiographic length was found to be identical in 11% cases; 35% were overestimates, and 54% were underestimates. The median underestimate was 2.45 mm whereas the median overestimate was 3.1 mm per distraction episode. In total, 95% of all ERC distractions were within ±10 mm of the radiographic length achieved over a median of nine distraction episodes.ConclusionsOur series is the most comprehensive MCGR series published to date, and we present a mechanical failure rate of 29%. Clinicians should be mindful of the discrepancies between ERC length and radiographic measurements of rod length; other modalities may be more helpful in this regard.

Limits to growth of forest biomass carbon sink under climate change

Widely recognized as a significant carbon sink, North American forests have experienced a history of recovery and are facing an uncertain future. This growing carbon sink is dictated by recovery from land-use change, with growth trajectory modified by environmental change. To address both processes, we compiled a forest inventory dataset from North America to quantify aboveground biomass growth with stand age across forest types and climate gradients. Here we show, the biomass grows from 90 Mg ha–1 (2000–2016) to 105 Mg ha–1 (2020 s), 128 Mg ha–1 (2050 s), and 146 Mg ha–1 (2080 s) under climate change scenarios with no further disturbances. Climate change modifies the forest recovery trajectory to some extent, but the overall growth is limited, showing signs of biomass saturation. The future (2080s) biomass will only sequester at most 22% more carbon than the current level. Given such a strong sink has limited growth potential, our ground-based analysis suggests policy changes to sustain the carbon sink.

Abstract B170: Novel immunodeficient rat models offer a unique platform for drug efficacy studies in human tumor xenografts

Abstract Immunodeficient mouse models seek to recapitulate the clinical features of advanced human cancers. However, drug efficacy testing and downstream analysis such as pharmacokinetic (PK) /pharmacodynamic (PD)-based studies are limited because of variability in tumor growth and kinetics, limited tumor growth potential, requiring the enrollment of larger numbers of mice in each treatment group to achieve required cohort sizes. Considering the distinctive advantages of rats in terms of their larger size, and ease of sampling at different time points for drug efficacy and clinical testing, we have developed unique immunodeficient rat models: the Rag2 knockout SDRTM rat (absence of mature B and T cells) and the Rag2/Il2rg double knockout SRGTM rat (absence of mature B and T cells, and lower NK cells) on a Sprague- Dawley background. Our group has previously demonstrated higher engraftment, better tumor kinetics, and increased tumor volume of xenografts in these rat models compared to available immunodeficient mouse strains for various cancer xenograft models. The purpose of the present study is to demonstrate the feasibility of drug efficacy studies using targeted molecular agents directed against cancer-associated drivers in our newly developed SDR and SRG rat models. We tested the efficacies of a combination treatment of an AKT inhibitor (MK2206) and MEK inhibitor (AZD6244), and a small-molecule activator of PP2A (SMAP) (DT-061) in a SDR rat xenograft model of human KRAS-mutant non-small cell lung cancer. 1 x 106 H358 cells were transplanted subcutaneously on the left hind flank in SDR rats. When tumor size reached 100-150 mm3, the rats were randomized to either control or treatment groups. The treatment groups received either a combination of AZD6244 with MK2206, or DT-061, and the vehicle-only control received n, n-dimethylacetamide + Solutol®/Kolliphor® HS 15, twice daily for 30 days by oral gavage. Both the kinase-inhibitors combination and SMAP treatment inhibited the growth of lung tumor xenograft in the SDR rats as shown by decreased mean tumor volume and fold changes in tumor volume compared to the control group. The combination treatment dose was just as effective at half the dose reported in previous mouse studies, demonstrating that lower dosing is sufficient for efficacy testing in rats. Importantly, no mortality, behavioral abnormalities, or changes in body weight were observed during the study, indicating a favorable tolerability profile in this model. We have also demonstrated that a human prostate cancer cell line VCaP, which has very poor engraftment and growth profiles in existing mouse models, grows well in our SRG rats. The SRG rat is now being used to study the chemotherapeutic efficacy of the benchmark androgen receptor inhibitor enzalutamide, in this VCaP tumor xenograft model. In addition, weekly blood sampling to measure PSA levels in the serum is being performed in the VCaP tumor xenograft efficacy study to demonstrate the flexibility of frequent sampling in the rat model to evaluate correlations between tumor growth and serum PSA levels. Citation Format: Kamesh Ravi, Fallon Noto, Christopher McClain, Angela Arey, Goutham Narla, Jack Crawford, Tseten Yeshi. Novel immunodeficient rat models offer a unique platform for drug efficacy studies in human tumor xenografts [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B170.

Value Added and Employment Growth in EU Primary Agriculture and Food Processing

SummaryThe relative economic importance of agri‐food production in EU Member States is in decline. This article examines the relationship between primary and processing agri‐food sectors at the Member State level in the European Union, focusing on value added and employment trends. Notable differences are observed in the performance of the agri‐food sector between the Member States, and substantially different economic developments are evident in the primary and processing sectors. The agricultural and food processing sectors remained more important in the economies of the EU Member States of Central and Eastern Europe than in those of Western Europe. The composition of primary agricultural output and the associated strength of the processing sector can partially determine the growth in incomes and employment that individual Member States can hope to derive from developments in their agri‐food sectors. This suggests that the agri‐food sectors in individual Member States have differing future income and employment‐generating capacity, and generally limited employment growth potential, with associated implications for the design of future agri‐food policy.