Woodland expansion in South African grassy biomes based on satellite observations (1990-2013): general patterns and potential drivers.

Increases in woody plant cover in savanna grassland environments have been reported on globally for over 50 years and are generally perceived as a threat to rangeland productivity and biodiversity. Despite this, few attempts have been made to estimate the extent of woodland increase at a national scale, principally due to technical constraints such as availability of appropriate remote sensing products. In this study, we aimed to measure the extent to which woodlands have replaced grasslands in South Africa's grassy biomes. We use multiseason Landsat data in conjunction with satellite L-band radar backscatter data to estimate the extent of woodlands and grasslands in 1990 and 2013. The method employed allows for a unique, nationwide measurement of transitions between grassland and woodland classes in recent decades. We estimate that during the 23-year study period, woodlands have replaced grasslands over ~57 000 km2 and conversely that grasslands have replaced woodlands over ~30 000 km2 , a net increase in the extent of woodland of ~27 000 km2 and an annual increase of 0.22%. The changes varied markedly across the country; areas receiving over 500 mm mean annual precipitation showed higher rates of woodland expansion than regions receiving <500 mm (0.31% yr-1 and 0.11% yr-1 , respectively). Protected areas with elephants showed clear loss of woodlands (-0.43% yr-1 ), while commercial rangelands and traditional rangelands showed increases in woodland extent (>0.19% yr-1 ). The woodland change map presented here provides a unique opportunity to test the numerous models of woody plant encroachment at a national/regional scale.

Discovery of (S,E)-3-(2-fluorophenyl)-N-(1-(3-(pyridin-3-yloxy)phenyl)ethyl)-acrylamide as a potent and efficacious KCNQ2 (Kv7.2) opener for the treatment of neuropathic pain.

Acrylamide (S)-6, a potent and efficacious KCNQ2 (Kv7.2) opener, demonstrated significant activity in two models of neuropathic pain and in the formalin test, suggesting that KCNQ2 openers may be useful in the treatment of neuropathic pain including diabetic neuropathy.

Effect of land cover and ecosystem mapping on ecosystem-risk assessment in the Little Karoo, South Africa.

Extinction-risk assessments aim to identify biological diversity features threatened with extinction. Although largely developed at the species level, these assessments have recently been applied at the ecosystem level. In South Africa, national legislation provides for the listing and protection of threatened ecosystems. We assessed how land-cover mapping and the detail of ecosystem classification affected the results of risk assessments that were based on extent of habitat loss. We tested 3 ecosystem classifications and 4 land-cover data sets of the Little Karoo region, South Africa. Degraded land (in particular, overgrazed areas) was successfully mapped in just one of the land-cover data sets. From <3% to 25% of the Little Karoo was classified as threatened, depending on the land-cover data set and ecosystem classification applied. The full suite of threatened ecosystems on a fine-scale map was never completely represented within the spatial boundaries of a coarse-scale map of threatened ecosystems. Our assessments highlight the importance of land-degradation mapping for the listing of threatened ecosystems. On the basis of our results, we recommend that when budgets are constrained priority be given to generating more-detailed land-cover data sets rather than more-detailed ecosystem classifications for the assessment of threatened ecosystems.

Viable mouse gene ablations that robustly alter brain Aß levels are rare.

BACKGROUND: Accumulation of amyloid-ß (Aß) peptide in the brain is thought to play a key pathological role in Alzheimer's disease. Many pharmacological targets have therefore been proposed based upon the biochemistry of Aß, but not all are equally tractable for drug discovery. RESULTS: To search for novel targets that affect brain Aß without causing toxicity, we screened mouse brain samples from 1930 novel gene knock-out (KO) strains, representing 1926 genes, using Aß ELISA assays. Although robust Aß lowering was readily apparent in brains from a BACE1 KO strain, none of the novel strains exhibited robust decreases in brain Aß, including a GPR3 KO strain, which had previously been proposed as an Aß target. However, significantly increased Aß was observed in brain samples from two KO strains, corresponding to genes encoding the glycosylphosphatidylinositol mannosyl transferase PIGZ and quinolinate phosphoribosyltransferase (QPRT). CONCLUSIONS: Thus, gene ablations that are permissive for mouse survival and that also have a robust effect on Aß levels in the brain are rare.

Pediatric wartime admissions to US military combat support hospitals in Afghanistan and Iraq: learning from the first 2,000 admissions.

BACKGROUND: Humanitarian and civilian emergency care accounts for up to one-third of US military combat support hospital (CSH) admissions. Almost half of these admissions are children. The purpose of this study is to describe the features of pediatric wartime admissions to deployed CSHs in Iraq and Afghanistan. METHODS: A retrospective database review was conducted using the Patient Administration Systems and Biostatistics Activity. Details of 2,060 pediatric admissions to deployed CSHs were analyzed. RESULTS: Nontraumatic diagnoses were responsible for 25% of all pediatric admissions. Penetrating injuries (76.3%) dominate the trauma admissions. The primary mechanisms of injury were gunshot wound (39%) followed by explosive injuries (32%). Categorizing the injuries by location revealed 38.3% extremity wounds, 23.6% torso injuries, 23.5% head, face, and neck injuries, and 13.3% burns. More than half of the children required two or more invasive or surgical procedures, 19.8% needed a transfusion, and 5.6% required mechanical ventilation. The mortality rate was 6.9%. The primary cause of death involved head trauma (29.5%) and burns (27.3%), followed by infectious diagnoses (7.2%). The case fatality rate for head injury and burn patients was 20.1% and 15.9%, respectively, in contrast to the fatality rate for all other diagnoses at 3.8% (p < 0.01). Excluding emergency department deaths, mortality rates for Afghanistan (6.2%) and Iraq (3.9%) significantly differ (p < 0.02). CONCLUSION: Pediatric patients account for approximately 10% of all CSH admissions in Afghanistan and Iraq. Burns and penetrating head injury account for the majority of pediatric mortality at the CSH.

Modification of the Laerdal SimBaby to include an integrated umbilical cannulation task trainer.

BACKGROUND: Given the emphasis on early vascular access via the umbilical vein in neonatal resuscitation it is essential that participants in neonatal resuscitation simulation training be given the opportunity to practice both the placement and use of an emergency umbilical venous catheter. By integrating available parts from the Laerdal catalog, combined with a few other inexpensive components, into a Laerdal SimBaby we were able to create a single, integrated neonatal simulator that could be used to practice both the placement and use of an emergent umbilical vein catheter. METHODS: To integrate an umbilical cannulation task trainer into the Laerdal SimBaby we used a specially modified replaceable umbilical cord and reservoir from the Laerdal Neonatal Resuscitation Baby. To this reservoir we attached a flanged outlet drain and drainage tube which allows for the infusion of medications and fluids. The modified SimBaby with integrated umbilical cannulation task trainer was validated for both face and content by simulation participants and a panel of neonatal resuscitation experts. RESULTS: The umbilical cannulation task trainer integrated well into the SimBaby and in no way altered the function of the mannequin. The modified Laerdal SimBaby was thought to work well by both participants and experts. Simulation participants liked having the chance to practice emergency umbilical vein cannulation and thought that the simulated umbilical cord was an important component in their learning experience. The expert panel thought that the modified SimBaby could be used for emergency umbilical vein cannulation skills training and that the addition gave the modified SimBaby major advantage over other simulators they had used to teach newborn resuscitation. DISCUSSION: We have developed a modification to the Laerdal SimBaby involving the integration of a usable umbilical cannulation task trainer. The modification was easily accomplished using available parts from the Laerdal catalog and a few other inexpensive components. Given the emphasis on early vascular access via the umbilical vein and the complexities involved with the administration of medications and fluids via this route we believe that a usable umbilical cannulation task trainer is essential to neonatal resuscitation simulation training. When modified as described the Laerdal SimBaby can act as a high-fidelity newborn simulator that allows participants to practice both the placement and use of an emergency umbilical vessel catheter. Given our positive experience we think others could apply the above modification to their own SimBaby.

Late presentation of diaphragmatic hernia in a Pacific Island pediatric population.

BACKGROUND: Congenital diaphragmatic hernia (CDH) usually presents at birth with respiratory distress syndrome (RDS) and has a high mortality rate if not promptly recognized and treated. The incidence of CDH is reported to be 0.8 - 1.0/10,000 registered births. Less than 3% present after the neonatal period. In the latter, ie. late-presenting CDH (L-pCDH), the prognosis is improved because pulmonary hypoplasia does not develop. With the creation and application of a store-and-forward telemedicine system to the Pacific Island Health Care Project (PIHCP), we have come to realize that this rare condition ie., (L-pCDH) occurs with unusual frequency in the United States Associated Pacific Islands (USAPIs), especially those of the Federated States of Micronesia (FSM). METHODS: Information concerning CDH was identified from the archived data base of the over 3, 100 cases of the PIHCP as well as the composite data base of Tripler Army Medical Center (TAMC). The cases of CDH diagnosed after the neonatal period (> 30 days of age) were considered to have L-pCDH. The study period was from 1997 - 2006. RESULTS: During the study period (1997-2006), 12 cases of CDH were referred from the PIHCP. There was 1 case of CDH born at TAMC (beneficiary from Micronesia) during the same period. The number of births over the 10-year period of study was similar for the referral base (PIHCP) and TAMC. Five of the 12 cases in which the age at diagnosis could be established, were L-pCDH from the PIHCP. The one case of CDH born at TAMC, during the 10 year period, was diagnosed in the neonatal period (< 30 days of age). DISCUSSION: These results confirm that CDH occurs with increased frequency in the USAPIs as contrasted to the frequency in the developed world. The incidence of L-p CDH is far in excess in the USAPIs. This review highlights the fact that this group of patients can be easily identified using tele-techology (attached chest X-rays demonstrating stomach and/or bowel gas in the chest) thus allowing remote diagnosis and referral for ultimate surgical correction of this potentially lethal condition. Infants and children with CDH: provided excellent graduate medical education (GME) for residents-in-training; are afforded advanced surgical treatment unavailable in the remote jurisdictions of the Pacific; and, following surgery, are restored to health to return to their homes so as to become contributing members of society. CONCLUSION: CDH, especially L-pCDH occurs with increased frequency in the USAPIs. The Web-based-store-and-forward telemedicine PIHCP allows for remote diagnosis. Patients so identified are transported to TAMC for definitive treatment. These patients provide excellent GME to our residents-in-training. Following surgical correction these patients are restored to health to return to their homes to mature and become contributing members of society.

Development of a PIV-vectored RSV vaccine: preclinical evaluation of safety, toxicity, and enhanced disease and initial clinical testing in healthy adults.

MEDI-534 is a bivalent live attenuated vaccine candidate against human respiratory syncytial virus (hRSV) and human parainfluenza virus type 3 (hPIV3) that was previously shown to be immunogenic and to protect rodents and African green monkeys from wild-type (wt) hRSV challenge. We performed further preclinical evaluations to address the safety of MEDI-534 prior to human testing. MEDI-534 did not predispose rodents to enhanced RSV disease following wt-RSV challenge, and the tissue tropism of the chimeric virus was confined to the respiratory tract. Representative clinical trial material did not produce toxicity in rats. In adults, MEDI-534 was highly restricted in replication, did not boost RSV and PIV3 antibody titers, and produced no medically significant vaccine-related adverse events thereby warranting further evaluation in pediatric populations.

The amyloid-beta rise and gamma-secretase inhibitor potency depend on the level of substrate expression.

The amyloid-beta (Abeta) peptide, which likely plays a key role in Alzheimer disease, is derived from the amyloid-beta precursor protein (APP) through consecutive proteolytic cleavages by beta-site APP-cleaving enzyme and gamma-secretase. Unexpectedly gamma-secretase inhibitors can increase the secretion of Abeta peptides under some circumstances. This "Abeta rise" phenomenon, the same inhibitor causing an increase in Abeta at low concentrations but inhibition at higher concentrations, has been widely observed. Here we show that the Abeta rise depends on the beta-secretase-derived C-terminal fragment of APP (betaCTF) or C99 levels with low levels causing rises. In contrast, the N-terminally truncated form of Abeta, known as "p3," formed by alpha-secretase cleavage, did not exhibit a rise. In addition to the Abeta rise, low betaCTF or C99 expression decreased gamma-secretase inhibitor potency. This "potency shift" may be explained by the relatively high enzyme to substrate ratio under conditions of low substrate because increased concentrations of inhibitor would be necessary to affect substrate turnover. Consistent with this hypothesis, gamma-secretase inhibitor radioligand occupancy studies showed that a high level of occupancy was correlated with inhibition of Abeta under conditions of low substrate expression. The Abeta rise was also observed in rat brain after dosing with the gamma-secretase inhibitor BMS-299897. The Abeta rise and potency shift are therefore relevant factors in the development of gamma-secretase inhibitors and can be evaluated using appropriate choices of animal and cell culture models. Hypothetical mechanisms for the Abeta rise, including the "incomplete processing" and endocytic models, are discussed.

(S,E)-N-[1-(3-heteroarylphenyl)ethyl]-3-(2-fluorophenyl)acrylamides: synthesis and KCNQ2 potassium channel opener activity.

Replacement of the morpholinyl moiety in (S,E)-N-[1-(3-morpholinophenyl)ethyl]-3-phenylacrylamide (1) with heteroaryl groups led to the identification of (S,E)-N-1-[3-(6-fluoropyridin-3-yl)phenyl]ethyl-3-(2-fluorophenyl)acrylamide (5) as a potent KCNQ2 potassium channel opener. Among this series of heteroaryl substituted acrylamides, (S,E)-N-1-[3-(1H-pyrazol-1-yl)phenyl]ethyl-3-(2-fluorophenyl)acrylamide (9) exhibits balanced potency and efficacy. The syntheses and the KCNQ2 opener activity of this series of acrylamides are described.

Gestational age-specific growth parameters for infants born at US military hospitals.

BACKGROUND: Military hospitals currently use gestational age-specific growth curves based on data collected in Denver, Colo, from 1948 to 1961. A number of population and environmental factors and medical practice changes may make these curves nonrepresentative. OBJECTIVE: Determine if presently used growth curves represent norms for infants born in military hospitals and create new curves for use in military hospitals. METHODS: Data were collected from medical records of tertiary- and primary-care military hospitals. We created growth curves created for birth weight, length, and head circumference and compared these curves at gestational ages 23-42 weeks to previously published norms and to 1998 national vital statistics. Racial and ethnic differences between groups were compared. A retrospective analysis of blood-glucose measurements for healthy term infants was performed to identify potential safety issues. RESULTS: Significant increases in growth parameters were noted for infants born in military hospitals. Specific racial and ethnic groups within the military also had an increase when compared with these groups in the United States as a whole. Less than 1% of infants classified as large for gestational age (LGA) according by old standards but average for gestational age (AGA) according to new curves experienced hypoglycemia. CONCLUSION: Published growth curves may not represent infants born in military hospitals. Term infants born in military hospitals as a group and in racial and ethnic subgroups are larger than term infants born in US civilian hospitals. Prospective use of curves will help to validate their long-term applicability in military and civilian nurseries.

Synthesis and KCNQ2 opener activity of N-(1-benzo[1,3]dioxol-5-yl-ethyl, N-[1-(2,3-dihydro-benzofuran-5-yl)-ethyl, and N-[1-(2,3-dihydro-1H-indol-5-yl)-ethyl acrylamides.

Bioisosteric replacement studies led to the identification of N-(1-benzo[1,3]dioxol-5-yl-ethyl)-3-(2-chloro-phenyl)-acrylamide ((S)-3) as a highly potent KCNQ2 opener, and 3-(2,6-difluoro-phenyl)-N-[1-(2,3-dihydro-benzofuran-5-yl)-ethyl]-acrylamide ((S)-4), and N-[1-(2,3-dihydro-1H-indol-5-yl)-ethyl]-3-(2-fluoro-phenyl)-acrylamide ((S)-5) as highly efficacious KCNQ2 openers. In contrast, their respective R enantiomers showed significantly less or no appreciable KCNQ2 opener activity even at the highest concentration tested (10 microM). Because of its high potency and moderate efficacy as well as its convenient synthesis, (+/-)-3 was selected as a reference compound for analyzing efficacies of KCNQ openers in electrophysiology studies. Compounds (S)-4 and (S)-5 demonstrated significant activity in reducing neuronal hyperexcitability in rat hippocampal slices. The synthesis and the KCNQ2 opener activity of these acrylamides are described.

Actinomyces species and cerclage placement in neonatal sepsis: a case report.

A 26-year-old female with a history of preterm labor and cerclage placement presented at 29 weeks gestation. Twin girls were delivered at 2917 weeks. Twin A presented with clinical sepsis at birth. Twin A's blood cultures became positive for Actinomyces species on day of life 15. Despite aggressive medical management twin A died at 35 days of life.

(S)-N-[1-(3-morpholin-4-ylphenyl)ethyl]- 3-phenylacrylamide: an orally bioavailable KCNQ2 opener with significant activity in a cortical spreading depression model of migraine.

(S)-N-[1-(3-Morpholin-4-ylphenyl)ethyl]-3-phenylacrylamide (2) was synthesized as an orally bioavailable KCNQ2 potassium channel opener. In a rat model of migraine, 2 demonstrated significant oral activity in reducing the total number of cortical spreading depressions induced by potassium chloride.