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/ This GIS-based study analyzes the distribution and management of woody riparian vegetation in California's Sacramento Valley and discusses the prospects for its conservation. Although forests were the predominant floodplain vegetation prior to extensive settlement, only 3.3% of floodplain was covered by forest in the late 1980s. This remaining forest was fragmented into 2607 patches with an average area of 3.1 ha. Only 180 patches were >10 ha, with three patches >100 ha. Despite over two decades of conservation efforts, these forests are essentially unpreserved: Only 14.5% of extant forests are in public ownership or on land managed primarily for biological conservation. Some privately owned forests represent opportunities for preservation, but owing to their small size and scattered distribution, reforestation would be necessary to obtain a high cover of forest over large areas. Additionally, high property values, existing land uses, and regulated hydrology constrain conservation efforts. As a consequence of these constraints, and current distribution and ownership patterns, preservation or restoration of substantial areas of riparian forest would be extremely expensive and would divert conservation resources from other habitats in this rapidly developing state. Therefore, efforts to conserve these forests should satisfy two criteria: (1) that the specific goals are attainable with available funding and existing human uses, and (2) funding the effort will result in more effective regional conservation than would funding the conservation of other habitats.KEY WORDS: Central Valley; Conservation; Floodplains; Geographic information systems; Riparian vegetationhttp://link.springer-ny.com/link/service/journals/00267/bibs/24n1p65.html

Comparison is made between a new asymmetric screen-film combination and a conventional screen-film combination for use in chest radiography. Seven anatomical features were assessed by three consultant radiologists in each of 51 film pairs. A preference was indicated if one system better demonstrated a particular feature. Alternatively, no preference was indicated if the feature was equally demonstrated by both systems or not demonstrated at all. Any pathology incidentally noted which remained unchanged between the two films was localized to lung, mediastinum or bone and marked in the same way. The asymmetric high contrast system scored higher than the conventional system for demonstration of anatomy in both mediastinum and lungs, but no difference emerged between the two systems in the demonstration of pathology. The asymmetric screen-film system showed improved mediastinal and, to a lesser degree, improved lung detail. Further assessment in necessary to define any associated improvement in diagnostic yield.

Androgens regulate body composition and skeletal muscle mass in males, but the molecular mechanisms are not fully understood. Recently, we demonstrated that trenbolone (a potent synthetic testosterone analogue that is not a substrate for 5-alpha reductase or for aromatase) induces myotrophic effects in skeletal muscle without causing prostate enlargement, which is in contrast to the known prostate enlarging effects of testosterone. These previous results suggest that the 5α-reduction of testosterone is not required for myotrophic action. We now report differential gene expression in response to testosterone versus trenbolone in the highly androgen-sensitive levator ani/bulbocavernosus (LABC) muscle complex of the adult rat after 6 weeks of orchiectomy (ORX), using real time PCR. The ORX-induced expression of atrogenes (Muscle RING-finger protein-1 [MuRF1] and atrogin-1) was suppressed by both androgens, with trenbolone producing a greater suppression of atrogin-1 mRNA compared to testosterone. Both androgens elevated expression of anabolic genes (insulin-like growth factor-1 and mechano-growth factor) after ORX. ORX-induced increases in expression of glucocorticoid receptor (GR) mRNA were suppressed by trenbolone treatment, but not testosterone. In ORX animals, testosterone promoted WNT1-inducible-signaling pathway protein 2 (WISP-2) gene expression while trenbolone did not. Testosterone and trenbolone equally enhanced muscle regeneration as shown by increases in LABC mass and in protein expression of embryonic myosin by western blotting. In addition, testosterone increased WISP-2 protein levels. Together, these findings identify specific mechanisms by which testosterone and trenbolone may regulate skeletal muscle maintenance and growth.

Depression is a common, major mental health problem with debilitating consequences for older adults. Although primary care is the principal setting for depression detection and treatment, symptoms are often underrecognized and undertreated in this setting, particularly for older African Americans (1–3). Compared with white persons, older African Americans are at greater risk for not receiving standard depression care (4–6) or participating in psychotherapy or other guideline treatments because of system-level (lack of access or minimal time spent on mental health) and patient-level (stigma or lack of symptom recognition) factors (7). Furthermore, prevalence rates of depressive symptoms among older African Americans, particularly those with chronic illnesses, may be as high as 30%, double the rates previously reported (8–11). Improving access to depression care for this group remains a public health concern. Depression has profound harmful health and psychosocial consequences, including increased risk for dementia (12), prolonged inflammatory responses after infection (13), functional decline (3, 14), poor quality of life, and death (3, 15). Even mild to moderate symptoms, if not successfully treated, are associated with poor health outcomes, erode quality of life, and increase health care utilization and costs (13, 14). Limitations of previous depression trials (psychosocial or medication) include an almost exclusive focus on primary care patients, lack of attention to approaches addressing barriers to accessing depression care, and lack of inclusion of older African Americans (16–27). Community- and home-based nonpharmacologic depression treatment approaches are promising, but few are tailored to or specifically tested in older African Americans (18, 25, 28–30). Building on previous trials (18, 27, 28), we designed the BTB (Beat the Blues) trial to address depressive symptoms in older African Americans. The trial represents a partnership between a university research center and senior center, with each contributing to intervention design, study plan, and execution. Senior centers are overlooked and underused settings providing disease prevention, health education, and social services to more than 1 million older adults daily, many of whom are vulnerable and underserved (20, 31). Yet, few senior centers offer depression care. Involving senior centers in depression care may reduce barriers to mental health services for older adults who may view clinical treatment as stigmatizing. The BTB trial was tailored to older African Americans. Recruitment strategies were spearheaded by the senior center, the program name reflected the language of the targeted group, behavioral activation was included as a treatment approach because activity is a preferred coping strategy of the targeted group, and stress reduction was tailored to participants’ personal preferences (32). We hypothesized that BTB participants would have reduced depressive symptoms (primary end point) and, secondarily, improvements in depression knowledge and efficacy, quality of life, physical function, anxiety, and behavioral activation at 4 months compared with wait-list control participants. We also considered whether control group participants showed similar benefits after receiving BTB and whether the initial BTB group maintained benefits at 8 months. Finally, we examined proportions of participants in remission, with clinically meaningful score reductions and improvement in diagnostic category.

Trenbolone (TREN), a potent testosterone analog, does not undergo 5[alpha]-reduction to the more potent metabolite dihydrotestosterone (DHT) and may produce androgenic effects without DHT-mediated ...

An aneurysm of the vein of Galen is a rare arteriovenous malformation of the central nervous system. Fetal manifestations have included nonimmune hydrops, hydrocephalus, and intracranial hemorrhage. This anomaly may be diagnosed prenatally by several imaging modalities. A cystic cranial mass was identified by ultrasound in a fetus at 30 weeks gestation. Both pulsed-wave Doppler and color-velocity imaging studies suggested aneurysm of the vein of Galen was the most likely diagnosis. The fetus demonstrated no evidence of hydrops on serial ultrasound examinations. A 2430 g female infant was delivered vaginally at 35 weeks gestation. Postnatal management included transarterial embolization of the vessels feeding the aneurysm with craniectomy, an intra-aneurysmal balloon, and vascular microcoils. Hydrocephalus developed and a ventriculo-peritoneal shunt was placed. The infant has grown appropriately in the first year of life. An aneurysm of the vein of Galen may be diagnosed prenatally by real-time ultrasound, pulsed-wave Doppler, color-velocity imaging, or magnetic resonance imaging. The presence of this malformation should prompt close follow-up for the remainder of the pregnancy. Careful obstetric management and early postnatal intervention may lead to a favorable outcome.

P-glycoprotein, the product of the MDR1 gene (multidrug resistance gene 1), is an energy-dependent efflux pump associated with treatment failure in some hematopoietic malignancies. Its expression is regulated during normal hematopoietic differentiation, although its function in normal hematopoietic cells is unknown. To identify cellular factors that regulate the expression of MDR1 in hematopoietic cells, we characterized the cis- and trans-acting factors mediating 12-O-tetradecanoylphorbol-13-acetate (TPA) activation of the MDR1 promoter in K562 cells. Transient-transfection assays demonstrated that an MDR1 promoter construct containing nucleotides -69 to +20 conferred a TPA response equal to that of a construct containing nucleotides -434 to +105. TPA induced EGR1 binding to the -69/+20 promoter sequences over a time course which correlated with increased MDR1 promoter activity and increased steady-state MDR1 RNA levels. The -69/+20 promoter region contains an overlapping SP1/EGR site. The TPA-responsive element was localized to the overlapping SP1/EGR site by using a synthetic reporter construct. A mutation in this site that inhibited EGR protein binding blocked the -69/+20 MDR1 promoter response to TPA. The expression of a dominant negative EGR protein also blocked the TPA response of the -69/+20 promoter construct. Finally, the expression of EGR1 was sufficient to activate a construct containing tandem MDR1 promoter SP1/EGR sites. These data suggest a role for EGR1 in modulating MDR1 promoter activity in hematopoietic cells.

Lead (Pb) poisoning of a pregnant heifer was diagnosed based upon clinical signs (head pressing, blindness, muscle twitching) and a blood lead concentration of 1.73 ppm. Blood and urinary Pb half-lives with CaNa2 EDTA/thiamine therapy were determined to be 2.08 and 1.38 days, respectively. Many cations (Ca, Fe, Zn, Na, Cu), including Pb, were excreted at higher concentrations in urine during therapy. Blood (0.425 ppm) and liver (4.85 ppm) Pb concentrations in the fetus were 71.7% and 84.3% of the same tissue Pb concentrations of the dam, indicating a significant transfer of Pb in utero. Severe polioencephalomalacia was described in the adult, and hepatic lysosomes with metallic electron densities were present in the fetus.

Background : Fetal lymphangiomas can occur in many different anatomic locations, including the most commonly seen nuchal cystic hygroma. Case : A fetus at 18 weeks' gestation was found to have a massive right axillary hygroma. The fetal karyotype was normal. Serial ultrasound examinations indicated progressive enlargement, but no hydrops. At 32 weeks' gestation, a left axillary hygroma was also diagnosed. The patient underwent cesarean delivery. Conclusion : Prenatal diagnosis of nuchal cystic hygromas has a high association with karyotypic abnormalities, hydrops, and fetal demise; however, this association may not apply to cystic lymphangiomas at other locations.

Objective To analyze the etiologies and outcomes for a southeastern section of the United States, and to organize an efficient approach to evaluation. Methods We reviewed 82 cases of non-immune hydrops presenting after 20 weeks' gestation over a 10-year period. Results Overall perinatal mortality was 86.6%. Fetuses diagnosed with hydrops before 24 weeks' gestation had a perinatal mortality of 95%, with nearly one-third having abnormal karyotypes. The etiology of hydrops diagnosed after 24 weeks' gestation was more likely to remain idiopathic or to be related to cardiothoracic abnormalities. Conclusion Before 24 weeks' gestation, the high risk of mortality and abnormal karyotype justifies offering families funipuncture in the hope of finding a treatable cause of non-immune hydrops. After 24 weeks' gestation, when fewer abnormal karyotypes are found, funipuncture may also be pivotal in diagnosing the cause of non-immune hydrops.

We evaluated the pregnancy outcome of all patients with elevations of both maternal serum alpha-fetoprotein and human chorionic gonadotropin since institution of combined serum screening at our program. After analysis of 34,404 samples, 99 patients were found to have significant elevations of both maternal serum alpha-fetoprotein and human chorionic gonadotropin. The ultrasound findings, amniocentesis results, and pregnancy outcomes were determined in each case. Sixty-six patients with singleton gestations met entry criteria. Pregnancy outcome information is available for 63 of these patients, 60% of whom had at least one complication. Thirty-three patients with multiple gestations met inclusion criteria. Pregnancy outcome information is available for 31 of these, 81% of whom had at least one complication. These patients had a high incidence of pregnancy related complications. This group would appear to be at higher risk than women with elevation of either maternal serum alpha-fetoprotein or human chorionic gonadotropin alone.

We evaluated the impact of tourist visits on Asian rhinos Rhonoceros unicornis in Chitwan National Park, Nepal, by comparing the rhino's behavior during and after elephant-borne tourist visits to their behavior before visits. During the visits, the rhinos spent more time on alert and less time feeding. Close approaches (especially those under 10 m) were more disruptive, and frequently displaced the rhinos from the meadows where they preferred to feed. Visits were short (20·7 min average) and rhinos that were not driven out re-established their pre-visit pattern of behavior within 14 min of the tourists' departure. Moreover, these rhinos' home ranges overlapped extensively and individuals ranged widely so that each individual's encounters with tourists were usually several days apart. Eliminating close approaches would make these tourist visits relatively benign. However, this finding cannot necessarily be extended to other populations that might have different social systems.

OBJECTIVE Both estrogen and mechanical loading regulate bone maintenance. However, mechanical overload seems less effective in enhancing bone mineral density (BMD) in estrogen-deficient women. The aim of this study was to determine whether estradiol (E2) influences early-phase bone adaptations to reambulation (REAMB) and/or rehabilitation exercises after hindlimb unloading (HLU) of ovariectomized rats. METHODS Eighty-one 5-month-old female Sprague-Dawley rats were randomized into the following groups: (1) intact controls, (2) ovariectomy (OVX), (3) OVX + E2, (4) OVX + 4 weeks of HLU, (5) OVX + E2 + HLU, (6) OVX + HLU + 2 weeks of quadrupedal REAMB, (7) OVX + E2 + HLU + REAMB, (8) OVX + HLU + REAMB + supplemental climbing, jumping, and balance exercises (EX), or (9) OVX + E2 + HLU + REAMB + EX. Serial dual-energy x-ray absorptiometry scans were performed to track total body bone characteristics throughout the study, and peripheral quantitative computerized tomography was used to determine distal femoral metaphyseal bone mineral characteristics. RESULTS Total body BMD increased by 4% to 8% in all animals receiving supplemental E2, whereas BMD did not change in animals without E2. OVX reduced trabecular BMD at the femoral metaphysis, and HLU exacerbated this loss while also reducing cortical BMD. E2 protected against OVX + HLU-induced bone loss at the femoral metaphysis. Conversely, REAMB did not alter BMD, regardless of estrogen status. In the absence of E2, REAMB + EX resulted in severe bone loss after OVX + HLU, with trabecular BMD and cortical BMD measurements that were 91% and 7% below those of controls, respectively (P ≤ 0.001). However, in the presence of E2, REAMB + EX did not negatively influence bone mineral characteristics. CONCLUSIONS E2 protects against bone loss resulting from combined OVX + HLU of rodents. In the absence of estrogen, exercise induces disadvantageous early-phase bone adaptations after extended disuse.

In this article we discuss the historical evolution of posttraumatic stress disorder (PTSD) following the Vietnam War with a focus on a article by Blanchard et al. published in the Journal in 1991, entitled: “Changes in plasma norepinephrine to combat-related stimuli among Vietnam veterans with posttraumatic stress disorder” (Blanchard et al., 1991). In this commentary, we discuss the significance of this brief article and developments in the PTSD field before, during, and after the Blanchard publication. Within this context, we discuss the eventual recognition in both the clinical and scientific fields that PTSD had a major neurobiological foundation. Finally, we examine the key implication of these discoveries from an epidemiologic, clinical, and a public health perspective.

The mutagenicity, metabolism, DNA adduction and induction of unscheduled DNA synthesis (UDS) of 1-nitropyrene and 1,8-dinitropyrene were investigated in the human hepatoma cell line HepG2. Previous results had demonstrated that 1-nitropyrene was both mutagenic at the hgprt locus and induced UDS in these cells. In the present study, we find that the dinitropyrenes, although highly mutagenic in Salmonella typhimurium, are not mutagenic and do not induce UDS in the HepG2. Although the rate of 1,8-dinitropyrene nitroreduction was less than that of 1-nitropyrene nitroreduction, this did not explain the lack of mutagenicity and UDS induction by the dinitropyrenes. Therefore, it is proposed that the arylhydroxylamine O-esterificase is not expressed in these cells. Since cytochrome P450-mediated C-oxidation is the predominant metabolic pathway in vivo, we sought to determine if an increase in the ratio of cytochrome P450-mediated C-oxidation over nitroreduction would result in increased or decreased DNA adducts in the HepG2. The administration of 2.5 microM 3-methylcholanthrene to the HepG2 increased the ratio of C-oxidation/nitroreduction from 2.8 +/- 1.9 to 50.4 +/- 46.1. This was accompanied by a decrease in the C8-guanyl adduct of 1-nitropyrene (via nitroreduction) from 18.7 +/- 7.0 to 4.8 +/- 1.7 fmoles/micrograms DNA, without any further increase in other 1-nitropyrene DNA adducts. These results suggest that the cytochrome P450-mediated metabolism of 1-nitropyrene to epoxides, phenols, and dihydrodiols is not an activation pathway in the HepG2 cells, and may explain the weak carcinogenicity of 1-nitropyrene in vivo, where cytochrome P450-mediated C-oxidation predominates. Images Figure 4.

The term pacifism is relatively new. It was not in the 1904 edition of The Complete Oxford Dictionary. The word popped into common usage not long after, though, to connote antiwar-ism and is attributed to the French, who originated the terms pacifisme and pacifiste from the French pacifique, which generally means to “make peace” or “calm.” The 2005 Merriam-Webster's Collegiate Dictionary defines pacifism as “opposition to war or violence as a means of settling disputes; specifically: refusal to bear arms on moral or religious grounds.” This simplistic definition belies the very complex and nuanced incarnations of pacifism. Keywords: pacifism; just-war pacifism; pragmatic pacifism; principled pacifism; humanistic pacifism; religious pacifism; ahimsa; nonviolence; abrahamic religions

Historically, the circulation was thought to be the primary source of androgens influencing skeletal muscle. However, a growing body of research indicates that skeletal muscle expresses several androgen-synthesizing enzymes, including 5a-reductase. The intramuscular expression of these enzymes suggests that skeletal muscle is capable of synthesizing bioactive androgens, which could induce myotrophic effects via intracrine action. Purpose: The aim of this brief review is to discuss recent research related to the intracrine and myotrophic roles of androgens, with particular focus on 5a-reductase as a myotrophic mediator. Methods: Included in the review are 17 reviews and 58 original studies that were identified by a systematic review from MEDLINE and deemed particularly relevant to our purpose. Results are summarized to provide an overview of 5a-reductase as a mediator of the myotrophic effects of androgens. In particular, discussions are included regarding androgen biosynthesis and androgen signaling within skeletal muscle, the effects of exercise on intramuscular androgen biosynthesis, and clinical applications of androgens and of a new class of myotrophic agonists termed selective androgen receptor modulator. Results: The ability of several peripheral tissues to synthesize bioactive androgens is well documented in the literature. Herein, we summarize newer studies that demonstrate that 1) skeletal muscle has the capability to synthesize both testosterone and dihydrotestosterone from dehydroepiandrosterone, which is present in abundance within the circulation, and 2) that exercise increases the expression of certain androgen-biosynthesizing enzymes within muscle. Conclusions: Intramuscularly synthesized androgens have the potential to influence skeletal muscle via intracrine action; however, their exact role in skeletal muscle development and maintenance requires further elucidation.

Background In preclinical studies, müllerian inhibiting substance (MIS) has a protective affect against breast cancer. Our objective was to determine whether serum MIS concentrations were associated with cancerous or precancerous lesions. Blood from 30 premenopausal women was collected and serum extracted prior to their undergoing breast biopsy to assess a suspicious lesion found on imaging or physical examination. Based on biopsy results, the serum specimens were grouped as cancer (invasive or ductal carcinoma in situ), precancer (atypical hyperplasia or lobular carcinoma in situ), or benign. Findings Serum from women with cancer and precancer (p = .0009) had lower MIS levels than serum from women with benign disease. Conclusion Our findings provide preliminary evidence for MIS being associated with current breast cancer risk, which should be validated in a larger population.

In this paper, we report the preliminary results of the sensitivity test for California Production, Exchange and Consumption Allocation System (PECAS). The sensitivity test includes three scenarios: PECAS Only, Integrated, and High Travel Cost. The PECAS Only scenario allocates production and consumption at a fixed travel cost from years 2000 to 2020. It shows that the floorspace growth is more affected by general plan than travel cost, and residential floorspace types have higher growth rates in suburb, exurb and rural areas. Additionally, nonresidential (industrial and commercial) floorspace types have higher growth rates in the inner urban areas. The Integrated scenario has a more compact land use pattern than the PECAS Only scenario. Compared with the Integrated scenario, the High Travel Cost scenario leads to more compact use. The results from all three scenarios imply that the model behaves as expected and the outputs are consistent with what has been theorized.

Fresno County is a rich agricultural area that faces rapid urbanization and farmland conversion. The county is participating in a strategic, multi-county planning initiative aimed at making sustainable and regionally cohesive land-use decisions. To inform this effort, we conducted a farmland conservation assessment and identified strategic farmlands for prioritization in future conservation efforts. We identified environmental and human predictor variables that affect the viability of existing farmland, used a geographic information system (GIS) to integrate them, and created a countywide strategic farmland conservation map. We compared our analysis to status quo methods of prioritization and found that with our model the spatial output of highly valued farmland was shifted, narrowed and located adjacent to some of the county's most urbanized areas. These findings are influencing growth policies and farmland conservation planning in Fresno County.

Brain derived neurotrophic factor (BDNF) is postulated to be an important mediator of exercise-induced neuroprotection. We tested the hypothesis that resistance exercise elevates circulating BDNF. Twenty healthy untrained college-aged males underwent a 5-week traditional or eccentric-enhanced progressive resistance training intervention. Blood was acquired at rest and 1, 30, and 60min following a standardized resistance exercise testing bout performed at baseline and at the completion of the intervention. Serum BDNF responses did not differ between the two groups at any time point during baseline or post-intervention testing; thus, all values were combined into a single cohort for further analysis. Resting BDNF was not altered by the exercise training intervention [23,304+/-1835pg/ml (baseline) vs. 19,433+/-1992pg/ml (post-intervention)]. Following the baseline resistance exercise bout, serum BDNF increased 32% (p

Hypothyroidism usually presents insidiously with symptoms such as fatigue, cold intolerance, and weight gain. Less common findings include myalgia, arthralgia, and joint effusion. In the patient described here, a triathlete, interpretation of early signs and symptoms as typical tendinitis led to months of treatment failure. Considering hypothyroidism in the differential diagnosis for patients who have overuse syndromes can expedite treatment. Definitive diagnosis rests on testing of serum thyroid hormone levels. Treatment, which is usually quickly effective, consists of gradually adjusted thyroid hormone replacement.

The objective of the study was to determine whether or not U.S. normal data for female Vertebral Bone Mineral Density is suitable for use in an Irish population. One hundred and fifty-six healthy Caucasian women of permanent Irish domicile had bone densitometry performed using single energy quantitative computed tomography of L2, L3 and L4 vertebrae. We found that comparison of our results to normal American data shows a slight and progressive increase in bone mineral content of postmenopausal American women with age relative to the Irish population. This difference is small and not sufficient to justify development of separate normal values for Irish women. We conclude that this discrepancy may be due to a combination of environmental and racial factors or to the more rigorous exclusion criteria applied in our study.

Holstein-Friesian cattle heterozygous for the deficiency of uridine monophosphate (UMP) synthase have half-normal activity of UMP synthase. The homozygous recessive genotype would result in little or no activity, has not been observed among live animals and apparently leads to embryonic mortality at approximately Day 40 of gestation. Activity of UMP synthase averaged 2.74 +/- 0.61 units/mg protein for 19 obligatory normal embryos (from normal x normal matings). Activity for 18 embryos from heterozygote x heterozygote matings yielded three non-overlapping groups as follows: (i) five presumed normals with greater than two-thirds normal activity, (ii) ten apparent heterozygotes with one-third to two-thirds normal activity and (iii) three putative homozygous recessive embryos with less than one-third normal activity. The distribution among these groups was consistent with the 1:2:1 ratio expected for autosomal inheritance. Conception of embryos homozygous recessive for this disorder was demonstrated.

GSK812397 is a potent entry inhibitor of X4-tropic strains of HIV-1, as demonstrated in multiple in vitro cellular assays (e.g., in peripheral blood mononuclear cells [PBMCs] and a viral human osteosarcoma [HOS] assay, mean 50% inhibitory concentrations [IC 50 s] ± standard errors of the means were 4.60 ± 1.23 nM and 1.50 ± 0.21 nM, respectively). The primary in vitro potency of GSK812397 was not significantly altered by the addition of serum proteins (2.55 [±0.12]-fold shift in the presence of human serum albumin and α-acid glycoprotein in the PBMC assay). Pharmacological characterization of GSK812397 in cell-based functional assays revealed it to be a noncompetitive antagonist of the CXCR4 receptor, with GSK812397 producing a concentration-dependent decrease in both an SDF-1-mediated chemotaxis and intracellular calcium release (IC 50 s were 0.34 ± 0.01 nM and 2.41 ± 0.50 nM, respectively). With respect to the antiviral activity of GSK812397, it was effective against a broad range of X4- and X4R5-utilizing clinical isolates. The potency and efficacy of GSK812397 were dependent on the individual isolate, with complete inhibition of infection observed with 24 of 30 isolates. GSK812397 did not show any detectable in vitro cytotoxicity and was highly selective for CXCR4, as determined using a wide range of receptors, enzymes, and transporters. Moreover, GSK812397 demonstrated acceptable pharmacokinetic properties and bioavailability across species. The data demonstrate that GSK812397 has antiviral activity against a broad range of X4-utilizing strains of HIV-1 via a noncompetitive antagonism of the CXCR4 receptor.

The main goal of this volume is to explain how governance authorities in a particular policy arena overcome fragmentation and solve vertical and horizontal collective action problems. Our chapter addresses this goal in two ways: first, we apply Norton Long's (1958) analysis of the ecology of games played in territorially defined metropolitan areas to regional governance, and second, we analyze the relationships between collaboration networks, trust, and political influence in the context of regional land-use and transportation policy. The central argument of the ecology of games framework is that local political outcomes emerge from actors pursuing their self-interest in multiple, interdependent, and rule-structured games. The resulting decisions lead to the type of fragmentation and decision externalities discussed throughout this volume. Collaborative partnerships and networks are considered potential self-organizing mechanisms for overcoming these dilemmas, and our empirical study explicitly examines the resulting patterns of cooperation, trust, and political influence. Our use of the ecology of games metaphor is partly a reaction to the burgeoning social science literature that examines the dynamics and effectiveness of collaborative processes as new institutions for political decision making. This literature itself has emerged in response to (and perhaps also partly caused) the widespread appearance of collaborative policy and its aliases in nearly every policy subsystem, especially environmental policy (O'Leary, Gerard, and Bingham 2006). These collaborative institutions are designed to alleviate many symptoms of institutional collective action (ICA) problems discussed in this book.

Recently, the development of selective androgen receptor modulators (SARMs) has been suggested as a means of combating the deleterious catabolic effects of hypogonadism, especially in skeletal muscle and bone, without inducing the undesirable androgenic effects (e.g., prostate enlargement and polycythemia) associated with testosterone administration. 17beta-Hydroxyestra-4,9,11-trien-3-one (trenbolone; 17beta-TBOH), a synthetic analog of testosterone, may be capable of inducing SARM-like effects as it binds to androgen receptors (ARs) with approximately three times the affinity of testosterone and has been shown to augment skeletal muscle mass and bone growth and reduce adiposity in a variety of mammalian species. In addition to its direct actions through ARs, 17beta-TBOH may also exert anabolic effects by altering the action of endogenous growth factors or inhibiting the action of glucocorticoids. Compared to testosterone, 17beta-TBOH appears to induce less growth in androgen-sensitive organs which highly express the 5alpha reductase enzyme (e.g., prostate tissue and accessory sex organs). The reduced androgenic effects result from the fact that 17beta-TBOH is metabolized to less potent androgens in vivo; while testosterone undergoes tissue-specific biotransformation to more potent steroids, dihydrotestosterone and 17beta-estradiol, via the 5alpha-reductase and aromatase enzymes, respectively. Thus the metabolism of 17beta-TBOH provides a basis for future research evaluating its safety and efficacy as a means of combating muscle and bone wasting conditions, obesity, and/or androgen insensitivity syndromes in humans, similar to that of other SARMs which are currently in development.

Government agencies that develop infrastructure such as roads, waterworks, and energy delivery often impact natural ecosystems, but they also have unique opportunities to contribute to the conservation of regional natural resources through compensatory mitigation. Infrastructure development requires a planning, funding, and implementation cycle that can frequently take a decade or longer, but biological mitigation is often planned and implemented late in this process, in a project-by-project piecemeal manner. By adopting early regional mitigation needs assessment and planning for habitat-level impacts from multiple infrastructure projects, agencies could secure time needed to proactively integrate these obligations into regional conservation objectives. Such practice can be financially and ecologically beneficial due to economies of scale, and because earlier mitigation implementation means potentially developable critical parcels may still be available for conservation. Here, we compare the integration of regional conservation designs, termed greenprints, with early multi-project mitigation assessment for two areas in California, USA. The expected spatial extent of habitat impacts and associated mitigation requirements from multiple projects were identified for each area. We used the reserve-selection algorithm MARXAN to identify a regional greenprint for each site and to seek mitigation solutions through parcel acquisition that would contribute to the greenprint, as well as meet agency obligations. The two areas differed in the amount of input data available, the types of conservation objectives identified, and local land-management capacity. They are representative of the range of conditions that conservation practitioners may encounter, so contrasting the two illustrates how regional advanced mitigation can be generalized for use in a wide variety of settings. Environmental organizations can benefit from this approach because it provides a platform for collaboration with infrastructure agencies. Alone, infrastructure agency mitigation obligations will not satisfy all greenprint objectives, but they can be a major contributor to the ongoing process of implementing ecologically sustainable regional plans. © 2009 by the author(s).