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OBJECTIVES To describe sexual behaviors and acceptability of receiving sexual and reproductive health (SRH) services among hospitalized adolescent males. METHODS We performed a cross-sectional survey of hospitalized adolescents. Eligible participants were males aged 14 to 20 years admitted at 2 academic medical centers. Outcome measures included reported healthcare utilization, sexual health behaviors (eg, sexual activity), contraception use, and acceptability of SRH discussions during a hospitalization. Results Among 145 participants, 42% reported a history of vaginal sex, 27% current sexual activity, 12% early sexual debut, and 22% 4 or more prior sexual partners. At last sex, condom use was reported by 63% and use of reversible contraception by 36%. Nearly half (45%) agreed that hospital-based SRH discussions were acceptable, particularly among those with history of sexual activity (P < .01). Some (12%) reported they had not accessed care in the past year when they felt they should. Conclusions Hospitalized males in our study had similar rates of sexual activity as compared with the general population but had higher rates of early sexual debut and number of prior partners, which are independently linked with negative sexual health outcomes (eg, sexually transmitted infections). Our participants found SRH discussions to be generally acceptable. These findings reveal opportunities to screen for unmet SRH needs and provide SRH education and services for adolescent males in the hospital.

Women's triathlon clothing designer Kristin Mayer established Betty Designs in 2010. Through the brand, Mayer created a visual embodiment of a self-defined sporting femininity that evoked strength and beauty. Mayer's personal struggle to define and defend a gendered aesthetic for women triathletes is at the heart of an oral history recorded for the Women in Triathlon History Project in 2019. A close reading of the Mayer oral history reveals a combination of rehearsed origin scripts, resistance, and discomposure. Considered together, the narrative and performative elements of the oral history raise the possibility of critical agency in female sporting apparel design and also demonstrate that competing feminisms and notions of empowerment combined to contest, shape, and reshape triathlon aesthetics. More broadly, the Mayer oral history reveals the extent to which oral testimonies reflect, negotiate, and craft versions of the pasts in active contributions to present and future discourse.

As landscape-scale conservation models grow in prominence, assessments of how wildlife utilise multiple-use landscapes are required to inform effective conservation and management planning. Such efforts should incorporate multi-species perspectives to maximise value for conservation, and should account for scale to accurately capture species-environment relationships. We show that the random forest machine learning algorithm can be used to model large-scale sign-based data in a multi-scale framework. We used this method to investigate scale-dependent habitat associations for 16 mammal species of high conservation importance across the southern Kavango Zambezi (KAZA) Transfrontier Conservation Area in Botswana and Zimbabwe. Our findings revealed substantial variation in factors shaping habitat use across species, and illustrate that different species often have divergent responses to the same environmental and anthropogenic factors, and differ in the scales at which they respond to them. For all variables across all species, scale optimisation most often selected our largest scale. Precipitation, soil nutrients, and vegetation appeared to be the most important factors determining mammal distributions, likely through their associations with food resources for herbivores and, in turn, prey availability for carnivores. Anthropogenic pressures also had an important influence, with many species selecting against areas with high cattle density. The variety of relationships with human density indicated that species vary in their tolerance of humans. We found a consistent positive relationship with areas under high protection, and negative relationship with unprotected and less-strictly protected areas. Policy implications. Through a novel application of random forest modelling to spoor data from 16 mammal species, this study highlights the importance of adopting a multi-scale, multi-species approach for decision-making processes that depend on understanding wildlife distributions and habitat associations, such as protected area and corridor prioritisation. The findings identify changing rainfall patterns and increasing livestock numbers as emerging trends that may impact wildlife distributions, both within sub-Saharan Africa and on a global scale. Wildlife management authorities should use modelling exercises and adaptive management to ensure that protected area networks remain fit for purpose under anticipated changes in rainfall under climate change, and explore initiatives that promote coexistence of wildlife and livestock.

OBJECTIVES To describe sexual health behaviors, contraceptive use, and pregnancy risk among hospitalized female adolescents. METHODS We conducted a cross-sectional survey of hospitalized female patients aged 14 to 21 years at 2 academic medical centers to assess sexual health behaviors, contraceptive use, contraceptive counseling receipt, and factors associated with pregnancy complications (eg, diabetes, teratogenic exposure). We calculated the validated Pregnancy Risk Index (PRI) (number per 100 who will become pregnant in the next year). RESULTS Among 177 participants (mean age 16 years, SD 1.5), 75 (43%) were sexually active. At last vaginal sex, 65% reported condom use; 49%, reversible contraception; and 12%, long-acting reversible contraception (LARC). Past-year contraceptive counseling was reported by 73% of sexually active female participants and was associated with increased use of reversible (P = .001) and dual contraception (P = .03) but not LARC (P = .24). The mean PRI among all participants was 4.75. Nearly three-quarters (73%) had a medical comorbidity or teratogenic exposure. Those with teratogenic medication use had the lowest PRI of 0.32 (P < .05), with 88% using reversible contraception and 31% using LARC. CONCLUSIONS Hospitalized female adolescents had a PRI similar to that of adolescents in the general population. However, nearly three-quarters had a medical comorbidity and/or teratogenic exposure, which increased risk for pregnancy complications. Contraceptive counseling was associated with increased reversible and dual contraception use but not LARC use. Efforts to improve comprehensive contraceptive counseling, highlighting LARC, are critically needed in this population.

Using an experimental approach, we analyzed the self-reported changes in farmers’ attitudes toward the African lion (Panthera leo) and a community-based lion conservation program (i.e., the Long Shields Community Guardians), before and after implementation. This program protects livestock and mitigates lion depredation through non-lethal means, with the aim of promoting human-lion coexistence. Results indicated a significant positive shift in attitudes of lions by farmers in the treatment group. This was also the case for farmers in what was recognized as a second unplanned treatment group, called the intermediate group, who learned about the program through communication within their peer network. This article contributed to the growing literature on conservation evaluation and demonstrates that people’s attitudes are valuable for assessing the impact of conservation programs.

Childbirth is an important female initiation experience. Most anthropologists of birth rely on Arnold van Gennep’s three-stage understanding of initiation rituals—separation, liminality, and return...

BACKGROUND AND OBJECTIVES: Many hospitalized adolescents are at increased risk for pregnancy complications due to an underlying medical condition, however sexual risk assessment is not consistently performed in this setting. While adolescents and their parents are supportive of sexual health discussion in the inpatient setting, a thorough understanding of factors that influence provision of this care among pediatric hospital physicians is lacking. This formative information is needed to facilitate efforts to improve and standardize clinical care provision. Our objective is to assess the frequency and factors that influence the provision of adolescent sexual and reproductive care by pediatric hospitalists. METHODS: We performed a cross-sectional computerized survey of hospitalists at 5 pediatric hospitals who cared for ≥1 adolescent (14–21 years old) in the past year. Sexual and reproductive care practices were assessed by using a 76-item novel survey informed by the theory of planned behavior. We used descriptive statistics to summarize the data. RESULTS: Sixty-eight pediatric hospitalists participated (49% response rate): 78% were women and 65% were aged 46 adolescents annually, including many who are at an increased risk for pregnancy complications due to teratogenic medication use or a comorbid condition. A majority felt that sexual and reproductive services are appropriate, although many endorsed barriers, including concern about follow-up after emergency contraception (63%) and time constraints (53%). Most reported insufficient knowledge regarding contraception (59%), desired contraception education (57%), and were likely to increase contraceptive provision if provided education (63%). Hospitalists rarely provided condoms or referral for an intrauterine device. CONCLUSIONS: Pediatric hospitalists frequently care for adolescents who are at risk for pregnancy complications and generally agree that reproductive care is appropriate in the inpatient setting. With these findings, we highlight the critical need for effective comprehensive reproductive health service interventions that are tailored to address the numerous actionable barriers identified in this study.

Ketamine is a synthetic drug with unique properties which started to be used therapeutically in humans in the 1970s and is now widely used in all fields of nursing. Ketamine acts on the central nervous system, primarily through inhibiting N-methyl-D-aspartate receptors. However, the precise understanding of its mechanisms of action remains elusive in many respects. Ketamine is frequently used as an anaesthetic in medical and surgical procedures and as an analgesic in children and adults. It is increasingly used in mental health settings to treat depression. It has potential to be used more often in areas such as palliative care and mental health care. This article reviews the physiological and pharmacological properties of ketamine, explores its main therapeutic uses, and considers the associated implications for nursing practice.

BACKGROUND AND OBJECTIVES: Adolescent substance use is associated with numerous adverse health outcomes. A hospitalization represents an opportunity to identify and address substance use. We sought to describe self-reported and documented substance use among hospitalized adolescents. METHODS: We conducted a cross-sectional survey of adolescents aged 14 to 18 years old admitted to two pediatric hospitals between August 2019 and March 2020. Using previously validated questions, we assessed the proportion of adolescents reporting ever, monthly, and weekly use of alcohol, marijuana, tobacco, electronic cigarettes, and other illicit drugs and nonmedical use of prescription medications. We reviewed medical records for substance use documentation. RESULTS: Among 306 respondents, 57% were older (16–18 years old), 53% were female, and 55% were of non-Hispanic white race and ethnicity. The most frequently reported substances ever used were alcohol (39%), marijuana (33%), and electronic cigarettes (31%); 104 (34%) respondents reported ever use of >1 substance. Compared with younger adolescents, those aged 16 to 18 years were more likely to report ever use of alcohol (29% vs 46%; P = .002), marijuana (22% vs 41%; P < .001), and ≥2 drugs (26% vs 40%; P = .009). A positive substance use history was rarely documented (11% of records reviewed), and concordance between documented and self-reported substance use was also rare. CONCLUSIONS: In this study of hospitalized adolescents, the most commonly reported substances used were alcohol, marijuana, and electronic cigarettes. Positive substance use documentation was rare and often discordant with self-reported substance use. Efforts to improve systematic screening for substance use and interventions for prevention and cessation in hospitalized adolescents are critically needed.

Conservation scientists are increasingly recognizing the need to evaluate the effectiveness of interventions to improve human–wildlife coexistence across different contexts. Here we assessed the long-term efficacy of the Long Shields Community Guardians programme in Zimbabwe. This community-based programme seeks to protect livestock and prevent depredation by lions Panthera leo through non-lethal means, with the ultimate aim of promoting human–lion coexistence. Using a quasi-experimental approach, we measured temporal trends in livestock depredation by lions and the prevalence of retaliatory killing of lions by farmers and wildlife managers. Farmers that were part of the Long Shields programme experienced a significant reduction in livestock loss to lions, and the annual number of lions subject to retaliatory killing by farmers dropped by 41% since the start of the programme in 2013, compared to 2008–2012, before the programme was initiated. Our findings demonstrate the Long Shields programme can be a potential model for limiting livestock depredation by lions. More broadly, our study demonstrates the effectiveness of community-based interventions to engage community members, improve livestock protection and ameliorate levels of retaliatory killing, thereby reducing human–lion conflict.

Trade-driven killing for body parts has long been a major cause of population decline for a number of big cat species. There are now worrying suggestions that commercialised illegal trade in body parts might become a threat for wild lions in Africa, and recent concerns have been raised that trade in captive-bred lion skeletons from South Africa may have stimulated demand for lion bones, claws, and teeth and thus incentivised commercially-driven, targeted poaching of wild lions for illegal trade. However, analysis of the prevalence of commercially-driven, targeted killing of lions for body parts is currently lacking for most major lion populations. In this study we make use of detailed, long-term records of mortality and body part removal from field sites in two of Africa’s lion population strongholds, the Hwange National Park and surrounds, Zimbabwe, within the Kavango Zambezi (KAZA) Transfrontier Conservation Area and the Ruaha landscape in Tanzania, to evaluate potential cases of commercially-driven part removal and targeted killings. We find no evidence of systemic targeted killing of lions for commercial trade at either site and suggest that the majority of part removals are opportunistic and culturally-driven. Nevertheless, we stress the requirement for vigilance around the issue of lion trade and support the development of further range-wide capacity to record wild lion mortality and body part removal data.

1. Environmental variations can influence the extent to which individuals interact with other individuals by changing the value of grouping. It is well known that many species can form and disband groups, often in response to the distribution and abundance of resources.2. While previous studies showed that resources influence the broad‐scale structure of animal groups, knowledge gaps remain on whether they affect fine‐scale patterns of association among individuals within groups.3. We quantify association patterns in African lions while simultaneously monitoring the abundance and distribution of prey. We test how social and ecological factors, including individual trait (age, sex, reproductive state) similarity and prey availability (prey abundance, dispersion, herd size and body size) affect within‐pride social structure in African lions.4. We found that individual decisions about associates depended on resource availability with individuals associating equally across all members of the pride when prey herds were scarce, aggregated or large bodied, and associating more exclusively (in subgroups of preferred associates) when prey herds were abundant, dispersed or small bodied. Individuals within lion prides seemed to be buffering against changes in prey availability by modulating their strength and density of connections with conspecifics when prides split into subgroups. The strength and density of connections among individuals within subgroups was greater when prey herds were large and lower when prey herds were dispersed or are large bodied.5. Our findings suggest that individual lions are making social decisions at both the subgroup level and the pride level, with decisions representing putatively fitness‐enhancing strategies. Individuals were typically shifting between having few strong connections and having many weaker connections depending on prevailing ecological conditions, with prey abundance, dispersion and body size having the greatest impact on decisions about splitting into subgroups. The maintenance of connections within prides and subgroups in the face of ecological change suggests that the fission–fusion nature of lion prides might be essential for the long‐term maintenance of social connections even when short‐term conditions do not allow them. More broadly, our study reveals how fission–fusion dynamics and ecological factors can simultaneously have an effect on animals across multiple levels of sociality. published

Transfrontier conservation areas (TFCAs) have the potential to provide havens for large carnivores while preserving connectivity across wider mixed-use landscapes. However, information on the status of species in such landscapes is lacking, despite being a prerequisite for effective conservation planning. We contribute information to this gap for leopard (Panthera pardus) in Africa, where the species is facing severe range contractions, using data from transect surveys of a 30,000km2 area across Botswana and Zimbabwe in the Kavango-Zambezi (KAZA) TFCA. We used occupancy models to assess how biotic, anthropogenic, and management variables influence leopard habitat use, and N-mixture models to identify variables influencing the species' relative abundance. Leopard were detected in 184 out of 413 sampling units of 64km2; accounting for imperfect detection resulted in mean detection probability p ¯ = 0.24 (SD = 0.06) and mean probability of site use ψ ¯ = 0.89 (SD = 0.20). Habitat use was positively influenced by prey availability and high protection. Relative abundance was best predicted by trophy hunting, which had a negative influence, while abundance was positively associated with high protection and availability of steenbok. Our findings suggest that securing prey populations should be a priority in conservation planning for leopard in Africa, and underline the necessity of preserving highly-protected areas within mixed-use landscapes as strongholds for large carnivores. Our findings also support calls for better assessment of leopard population density in trophy hunting areas, and illustrate the value of N-mixture models to identify factors influencing relative abundance of large carnivores.

We explored the perceptions held by subsistence farmers (living in communal lands within the CAMPFIRE programme area in northwestern Zimbabwe) towards the African lion (Panthera leo) and related conservation interventions undertaken by management authorities. Conceptually guided by the cognitive hierarchy, we used a semi-structured, face-to-face interview format to collect data across three different farming communities bordering Hwange and Zambezi National Parks. Ordinal regression models were used to analyse the data. Our results illustrate that farmers' perceptions towards lions were strongly negative and appeared to be associated with the geographic location in which the farmer lived, as well as the farmer's ethnic group. We also found that perceptions towards lions were not associated with specific livestock losses or to the potential benefits farmers received from wildlife conservation, e.g. school classroom blocks or road improvements. Instead, we suggest that fear of lions and perceived risk to livestock or human wellbeing may play a stronger role in shaping farmers' perceptions compared to actual livestock losses. Moreover, we suggest that sharing information across farmer social networks within a community area, along with the potential for media attention over sensational events, may also influence perceptions towards lions. Our results contribute a baseline dataset for future applied research in this area, and provide insight into developing locally-meaningful conservation interventions, including the type of information to be shared, channels for communication, and the benefits derived from participating in wildlife conservation.

Trophy hunting plays a significant role in wildlife conservation in some contexts in various parts of the world. Yet excessive hunting is contributing to species declines, especially for large carnivores. Simulation models suggest that sustainable hunting of African lions may be achieved by restricting offtakes to males old enough to have reared a cohort of offspring. We tested and expanded criteria for an age-based approach for sustainably regulating lion hunting. Using photos of 228 known-age males from ten sites across Africa, we measured change in ten phenotypic traits with age and found four age classes with distinct characteristics: 1-2.9 years, 3-4.9 years, 5-6.9 years, and ≥7 years. We tested the aging accuracy of professional hunters and inexperienced observers before and after training on aging. Before training, hunters accurately aged more lion photos (63%) than inexperienced observers (48%); after training, both groups improved (67-69%). Hunters overestimated 22% of lions

A central question in the study of predator-prey relationships is to what extent prey behaviour is determined by avoidance of predators. Here, we test whether the long-term risk of encountering lions and the presence of lions in the vicinity influence the behaviour of large African herbivores at waterholes through avoidance of high-risk areas, increases in group size, changes in temporal niche or changes in the time spent in waterhole areas. In Hwange National Park, Zimbabwe, we monitored waterholes to study the behaviour of nine herbivore species under different risks of encountering lions. We radio-collared 26 lions in the study area which provided the opportunity to monitor whether lions were present during observation sessions and to map longer-term seasonal landscapes of risk of encountering lions. Our results show that the preferred prey species for lions (buffalo, kudu and giraffe) avoided risky waterholes. Group size increased as encounter risk increased for only two species (wildebeest and zebra), but this effect was not strong. Interestingly, buffalo avoided the hours of the day which are dangerous when the long-term and short-term risks of encountering lions were high, and all species showed avoidance of waterhole use at night times when lions were in the vicinity. This illustrates well how prey can make temporal adjustments to avoid dangerous periods coinciding with predator hunting. Additionally, many herbivores spent more time accessing water to drink when the long- and short-term risks of encountering lions were high, and they showed longer potential drinking time when the long-term risk of encountering lions was high, suggesting higher levels of vigilance. This study illustrates the diversity of behavioural adjustments to the risk of encountering a predator and how prey respond differently to temporal variations in this risk. © Springer-Verlag 2009.

© 2015 Elsevier B.V. Livestock depredation frequently results in retaliatory killing of carnivores by people. An understanding of the ecological and sociological factors that precipitate this conflict is essential to mitigation. We investigated the seasonality of lion (Panthera leo) depredation incidents in relation to cattle (Bos primigenius) herding patterns in Tsholotsho Communal Land and Ngamo Forest adjacent to Hwange National Park, Zimbabwe. Cattle from 14 villages along the protected area (PA) boundaries were fitted with GPS data loggers (2010-2012), and depredation incidents systematically recorded (2008-2012). More cattle were killed by lions during the wet season (October to May) than during the dry months (June to September). In the wetter months, corresponding to the growing season and the need to protect crops, cattle were herded further from their home enclosures, closer to PA boundaries and into more wooded habitats. By contrast, cattle remained closer to home, further from PAs and were left to graze in fallow fields close to villages in the dry months. Seasonal use of wooded areas distant to villages and close to PA boundaries during the growing season increases vulnerability of cattle to lion depredation. In the dry months, cattle grazing close to villages benefit from the close proximity of people, resulting in a lower incidence of depredation. Approaches to mitigate livestock depredation should focus on improving herd protection during the wet season when cattle graze far from villages. Strategies such as communal herding, more intensive livestock guarding and, where possible, avoidance of heavily wooded habitats close to PAs should be encouraged.

Scale influences habitat selection. We used data from 30 global positioning system radiocollared lions (Panthera leo) collected between 2003 and 2007 in Hwange National Park, Zimbabwe, and information from 227 locations where lions had made kills, to assess how lions select habitat at 3rd-order habitat selection (selection of habitats within home ranges) and 4th-order habitat selection (selection of kill sites within the habitats used). Within home range, lions preferentially selected bushed grasslands and sites close to water holes, which are both characterized by high prey abundance. However, lions preferentially killed in thickets, where prey abundance was not the highest but where prey catchability may be higher because of dense vegetation. Our results support the suggestion that there are different determinants of habitat selection at different scales with prey abundance being the main driver of habitat selection at 3rd-order and prey catchability the main driver at 4rth-order habitat selection. © 2012 American Society of Mammalogists.

Technology usability, especially electronic health record (EHR) usability, is a global concern for clinicians. Despite critical user experience (UX) issues, nurses are not vocal about interactions with health IT. The purpose of this project was to identify nurses’ health IT UX issues and propose solutions for them. Using a snowball sampling technique, 25 experts were interviewed using a semi-structured format. Three themes emerged from content analysis (1) The Burdens of Health IT, (2) The Voice of Nursing, and (3) We Need a New Vision. Lack of cognitive support underscores the burden theme. The voice of nursing is missing throughout the systems life cycle, and a need exists for new visions of EHRs and training delivery. Solutions include the need for national leadership, modular redesign of EHRs to support the way nurses think and do work, and a concerted effort to incorporate UX methods into health IT design in the future.

CYP2E1 is widely accepted as the sole form of cytochrome P450 responsible for alcohol-mediated increases in acetaminophen (APAP) hepatotoxicity. However, we previously found that alcohol [ethanol and isopentanol (EIP)] causes increases in APAP hepatotoxicity in Cyp2e1(-/-) mice, indicating that CYP2E1 is not essential. Here, using wild-type and Cyp2e1(-/-) mice, we investigated the relative roles of CYP2E1 and CYP3A in EIP-mediated increases in APAP hepatotoxicity. We found that EIP-mediated increases in APAP hepatotoxicity occurred at lower APAP doses in wild-type mice (300 mg/kg) than in Cyp2e1(-/-) mice (600 mg/kg). Although this result suggests that CYP2E1 has a role in the different susceptibilities of these mouse lines, our findings that EIP-mediated increases in CYP3A activities were greater in wild-type mice compared with Cyp2e1(-/-) mice raises the possibility that differential increases in CYP3A may also contribute to the greater APAP sensitivity in EIP-pretreated wild-type mice. At the time of APAP administration, which followed an 11 h withdrawal from the alcohols, alcohol-induced levels of CYP3A were sustained in both mouse lines, whereas CYP2E1 was decreased to constitutive levels in wild-type mice. The CYP3A inhibitor triacetyloleandomycin (TAO) decreased APAP hepatotoxicity in EIP-pretreated wild-type and Cyp2e1(-/-) mice. TAO treatment in vivo resulted in inhibition of microsomal CYP3A-catalyzed activity, measured in vitro, with no inhibition of CYP1A2 and CYP2E1 activities. In conclusion, these findings suggest that both CYP3A and CYP2E1 contribute to APAP hepatotoxicity in alcohol-treated mice.

Data were collected on species killed by lions Panthera leo in Hwange National Park, Zimbabwe between 1998 and 2004. Lions killed predominantly large to medium-sized herbivores, concentrating on buffalo Syncerus caffer, elephant Loxodonta africana, giraffe Giraffa camelopardalis, wildebeest Connochaetes taurinus and zebra Equus burchelli. These species made up 83% of all lion kills found and 94% of the biomass of kills actually observed. Elephant calves made up an unusually large proportion of lion prey during the study period (23% of kills recorded). All elephants killed were dependent juveniles. Elephant calves appear more vulnerable during the dry months of the year, particularly in years of below average rainfall. Elephant calves are usually well protected. However, high-density aggregations of elephants around limited water sources during the dry season may deplete local food resources, forcing elephant herds to travel large distances between water and forage. Under these circumstances, elephant calves may become lost or separated from family groups, accounting for their high incidence in lion diet. © 2006 The Authors.

The objective of this study was to determine whether Toll-like receptor 4 (TLR4) has a role in alcohol-mediated acetaminophen (APAP) hepatotoxicity. TLR4 is involved in the inflammatory response to endotoxin. Others have found that ethanol-mediated liver disease is decreased in C3H/HeJ mice, which have a mutated TLR4 resulting in a decreased response to endotoxin compared with endotoxin-responsive mice. In the present study, short-term (1 wk) pretreatment with ethanol plus isopentanol, the predominant alcohols in alcoholic beverages, caused no histologically observed liver damage in either C3H/HeJ mice or endotoxin-responsive C3H/HeN mice, despite an increase in nitrotyrosine levels in the livers of C3H/HeN mice. In C3H/HeN mice pretreated with the alcohols, subsequent exposure to APAP caused a transient decrease in liver nitrotyrosine formation, possibly due to competitive interaction of peroxynitrite with APAP producing 3-nitroacetaminophen. Treatment with APAP alone resulted in steatosis in addition to congestion and necrosis in both C3H/HeN and C3H/HeJ mice, but the effects were more severe in endotoxin-responsive C3H/HeN mice. In alcohol-pretreated endotoxin-responsive C3H/HeN mice, subsequent exposure to APAP resulted in further increases in liver damage, including severe steatosis, associated with elevated plasma levels of TNF-α. In contrast, alcohol pretreatment of C3H/HeJ mice caused little to no increase in APAP hepatotoxicity and no increase in plasma TNF-α. Portal blood endotoxin levels were very low and were not detectably elevated by any of the treatments. In conclusion, this study implicates a role of TLR4 in APAP-mediated hepatotoxicity.

The lymphotoxin axis is important for the maintenance of several specialized lymphoid microenvironments in secondary lymphoid tissue. Lymphoid-tissue architecture is highly plastic and requires continual homeostatic signaling to maintain its basal functional state. The cellularity of lymph nodes in adult mice was reduced by systemic blockade of lymphotoxin-beta receptor (LTbeta R) signaling with a soluble decoy receptor both in resting and reactive settings. This reduction in cellularity resulted from greatly impaired lymphocyte entry into lymph nodes due to decreased levels of peripheral lymph node addressing (PNAd) and MAdCAM on high endothelial venules (HEV). LTbeta R signaling was required to maintain normal levels of RNA expression of MAdCAM, and also of PNAd by regulating the expression of key enzymes and scaffold proteins required for its assembly. Thus, the homeostatic maintenance of functional HEV status in adult mice relies largely on LTbeta R signaling.

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent form of human hepatic disease and feeding mice a high-fat, high-caloric (HFHC) diet is a standard model of NAFLD. To better understand the genetic basis of NAFLD, we conducted an expression quantitative trait locus (eQTL) analysis of mice fed a HFHC diet. Two-hundred sixty-five (A/J × C57BL/6J) F2 male mice were fed a HFHC diet for 8 wk. eQTL analysis was utilized to identify genomic regions that regulate hepatic gene expression of Xbp1s and Socs3. We identified two overlapping loci for Xbp1s and Socs3 on Chr 1 (164.0–185.4 Mb and 174.4–190.5 Mb, respectively) and Chr 11 (41.1–73.1 Mb and 44.0–68.6 Mb, respectively), and an additional locus for Socs3 on Chr 12 (109.9–117.4 Mb). C57BL/6J-Chr 11A/J/ NaJ mice fed a HFHC diet manifested the A/J phenotype of increased Xbp1s and Socs3 gene expression (P < 0.05), whereas C57BL/6J-Chr 1A/J/ NaJ mice retained the C57BL/6J phenotype. In addition, we replicated the eQTLs on Chr 1 and Chr 12 (LOD scores ≥3.5) using mice from the BXD murine reference panel challenged with CCl4 to induce chronic liver injury and fibrosis. We have identified overlapping eQTLs for Xbp1 and Socs3 on Chr 1 and Chr 11, and consomic mice confirmed that replacing the C57BL/6J Chr 11 with the A/J Chr 11 resulted in an A/J phenotype for Xbp1 and Socs3 gene expression. Identification of the genes for these eQTLs will lead to a better understanding of the genetic factors responsible for NAFLD and potentially other hepatic diseases.

When was the last time that parents told you they enjoyed their children's homework assignment because it gave them a chance to communicate with their children? That is exactly what happened in one middle-grades classroom. Jane Hunt, a seventh-grade mathematics teacher, used a number-line activity based on students' individual timelines to help her students understand the concepts of integers and rational numbers. These personal lifelines connected mathematics with language arts and other subjects. The project allowed for concept development through real-life experiences, with the added bonus that many parents became enthusiastic about opportunities to share family history with their children.

The effects of radioactive contamination from Chernobyl on decomposition of plant material still remain unknown. We predicted that decomposition rate would be reduced in the most contaminated sites due to an absence or reduced densities of soil invertebrates. If microorganisms were the main agents responsible for decomposition, exclusion of large soil invertebrates should not affect decomposition. In September 2007 we deposited 572 bags with uncontaminated dry leaf litter from four species of trees in the leaf litter layer at 20 forest sites around Chernobyl that varied in background radiation by more than a factor 2,600. Approximately one quarter of these bags were made of a fine mesh that prevented access to litter by soil invertebrates. These bags were retrieved in June 2008, dried and weighed to estimate litter mass loss. Litter mass loss was 40 % lower in the most contaminated sites relative to sites with a normal background radiation level for Ukraine. Similar reductions in litter mass loss were estimated for individual litter bags, litter bags at different sites, and differences between litter bags at pairs of neighboring sites differing in level of radioactive contamination. Litter mass loss was slightly greater in the presence of large soil invertebrates than in their absence. The thickness of the forest floor increased with the level of radiation and decreased with proportional loss of mass from all litter bags. These findings suggest that radioactive contamination has reduced the rate of litter mass loss, increased accumulation of litter, and affected growth conditions for plants.

Large carnivores inhabiting ecosystems with heterogeneously distributed environmental resources with strong seasonal variations frequently employ opportunistic foraging strategies, often typified by seasonal switches in diet. In semi-arid ecosystems, herbivore distribution is generally more homogeneous in the wet season, when surface water is abundant, than in the dry season when only permanent sources remain. Here, we investigate the seasonal contribution of the different herbivore species, prey preference and distribution of kills (i.e. feeding locations) of African lions in Hwange National Park, Zimbabwe, a semi-arid African savanna structured by artificial waterholes. We used data from 245 kills and 74 faecal samples. Buffalo consistently emerged as the most frequently utilised prey in all seasons by both male (56%) and female (33%) lions, contributing the most to lion dietary biomass. Jacobs' index also revealed that buffalo was the most intensively selected species throughout the year. For female lions, kudu and to a lesser extent the group "medium Bovidae" are the most important secondary prey. This study revealed seasonal patterns in secondary prey consumption by female lions partly based on prey ecology with browsers, such as giraffe and kudu, mainly consumed in the early dry season, and grazers, such as zebra and suids, contributing more to female diet in the late dry season. Further, it revealed the opportunistic hunting behaviour of lions for prey as diverse as elephants and mice, with elephants taken mostly as juveniles at the end of the dry season during droughts. Jacobs' index finally revealed a very strong preference for kills within 2 km from a waterhole for all prey species, except small antelopes, in all seasons. This suggested that surface-water resources form passive traps and contribute to the structuring of lion foraging behaviour.

We test two hypotheses that could account for patch departure by large mammalian carnivores. One hypothesis is the unsuccessful-hunt hypothesis, where carnivores leave an area after an unsuccessful hunt but continue hunting in the same area after a successful hunt. The second hypothesis is the patch-disturbance hypothesis, where carnivores depart the area after a successful hunt because of behavioral responses of prey to predator presence. We used global positioning system collars to monitor the movements of African lions (Panthera leo) and identified their kill sites to distinguish between these two hypotheses. Lions moved to a different area (≥5 km away) after 87% of the kills, which supports the patch-disturbance hypothesis for patch-departure behavior of large mammalian carnivores.

Immunohistochemical techniques were applied to rheumatoid synovium in order to detect components of coagulation and fibrinolysis pathways within these tissues. These techniques revealed an intact coagulation pathway and plasminogen activator inhibitor-2 associated with macrophagelike cells that were present throughout these tissues, especially in subsurface areas. Cell-associated thrombin generation appeared to account for conversion of abundant fibrinogen to fibrin. Occasional macrophage-like cells also stained for urokinase but tissue-type plasminogen activator and plasminogen activator inhibitor-1 were restricted to vascular endothelium. Intense synovial fibrin deposition (with the limited evidence for associated fibrinolysis) may contribute to local inflammation and explain certain clinical features of rheumatoid arthritis. These findings suggest novel treatment hypotheses for this disease.

The purpose of this study was to purify and characterize the forms of cytochrome P-450 induced in chicken liver by acetone or ethanol. Using high performance liquid ion-exchange chromatography, we were able to isolate at least four different forms of cytochrome P-450 which were induced by acetone in chicken liver. All four forms of cytochrome P-450 proved to be distinct proteins, as indicated by their N-terminal amino acid sequences and their reconstituted catalytic activities. Two of these forms, also induced by glutethimide in chicken embryo liver, appeared to be cytochromes P450IIH1 and P450IIH2. Both of these cytochromes P-450 have identical catalytic activities towards benzphetamine demethylation. However, they differ in their abilities to hydroxylate p-nitrophenol and to convert acetaminophen into a metabolite that forms a covalent adduct with glutathione at the 3-position. Another form of cytochrome P-450 induced by acetone is highly active in the hydroxylation of p-nitrophenol and in the conversion of acetaminophen to a reactive metabolite, similar to reactions catalysed by mammalian cytochrome P450IIE. Yet the N-terminal amino acid sequence of this form has only 30-33% similarity with cytochrome P450IIE purified from rat, rabbit and human livers. A fourth form of cytochrome P-450 was identified whose N-terminal amino acid sequence and enzymic activities do not correspond to any mammalian cytochromes P-450 reported to be induced by acetone or ethanol.

The pregnane X receptor (PXR) is a transcriptional regulator of xenobiotic metabolizing enzymes, including cytochrome P450 3A (CYP3A), and transporters. Pretreatment of mice and rats with inducers of CYP3A increases acetaminophen (APAP) hepatotoxicity. In untreated mice, the amount of hepatic CYP3A11 mRNA is 4-fold greater in PXR(-/-) mice compared to wild-type mice (Guo et al., 2003), a finding anticipated to increase APAP hepatotoxicity in PXR(-/-) mice. We investigated APAP hepatotoxicity in wild-type and PXR(-/-) mice in a C57BL/6 background, with APAP administered by gavage. Despite a 2.5-fold higher level of total hepatic CYP3A protein and a 3.6-fold higher level of CYP3A activity compared to wild-type mice, PXR(-/-) mice were less sensitive to APAP hepatotoxicity. Hepatic levels of CYP2E1 were identical in the two mouse lines, but hepatic CYP1A2 levels were 3-fold greater in wild-type mice compared to PXR(-/-) mice. Caffeine, an inhibitor of CYP1A2 activity and an enhancer of CYP3A activity, decreased APAP hepatotoxicity in wild-type mice. APAP uptake was 1.5-fold greater in wild-type mice compared to PXR(-/-) mice. No significant differences in the formation of APAP glucuronide and sulfate-conjugated metabolites were observed between wild-type and PXR(-/-) mice. Glutathione levels were similar in the two mouse lines and were transiently decreased to similar amounts after APAP administration. Our finding that APAP hepatotoxicity was decreased in PXR(-/-) mice indicates that PXR is an important modulator of APAP hepatotoxicity, through positive modulation of constitutive CYP1A2 expression and possibly through increased APAP absorption.

The pregnane X receptor (PXR) is a transcriptional regulator of xenobiotic metabolizing enzymes, including cytochrome P450 3A (CYP3A), and transporters. Pretreatment of mice and rats with inducers of CYP3A increases acetaminophen (APAP) hepatotoxicity. In untreated mice, the amount of hepatic CYP3A11 mRNA is 4-fold greater in PXR(-/-) mice compared to wild-type mice (Guo et al., 2003), a finding anticipated to increase APAP hepatotoxicity in PXR(-/-) mice. We investigated APAP hepatotoxicity in wild-type and PXR(-/-) mice in a C57BL/6 background, with APAP administered by gavage. Despite a 2.5-fold higher level of total hepatic CYP3A protein and a 3.6-fold higher level of CYP3A activity compared to wild-type mice, PXR(-/-) mice were less sensitive to APAP hepatotoxicity. Hepatic levels of CYP2E1 were identical in the two mouse lines, but hepatic CYP1A2 levels were 3-fold greater in wild-type mice compared to PXR(-/-) mice. Caffeine, an inhibitor of CYP1A2 activity and an enhancer of CYP3A activity, decreased APAP hepatotoxicity in wild-type mice. APAP uptake was 1.5-fold greater in wild-type mice compared to PXR(-/-) mice. No significant differences in the formation of APAP glucuronide and sulfate-conjugated metabolites were observed between wild-type and PXR(-/-) mice. Glutathione levels were similar in the two mouse lines and were transiently decreased to similar amounts after APAP administration. Our finding that APAP hepatotoxicity was decreased in PXR(-/-) mice indicates that PXR is an important modulator of APAP hepatotoxicity, through positive modulation of constitutive CYP1A2 expression and possibly through increased APAP absorption.

A lymphotoxin-β (LTβ) receptor-Ig fusion protein (LTβR-Ig) was used to evaluate the importance of the lymphotoxin/LIGHT axis in the development and perpetuation of arthritis. Prophylactic treatment with the inhibitor protein LTβR-Ig blocked the induction of collagen-induced arthritis in mice and adjuvant arthritis in Lewis rats. Treatment of mice with established collagen-induced arthritis reduced the severity of arthritic symptoms and joint tissue damage. However, in a passive model of anti-collagen Ab-triggered arthritis, joint inflammation was not affected by LTβR-Ig treatment precluding LT/LIGHT involvement in the very terminal immune complex/complement/FcR-mediated effector phase. Collagen-II and Mycobacterium-specific T cell responses were not impaired, yet there was evidence that the overall response to the mycobacterium was blunted. Serum titers of anti-collagen-II Abs were reduced especially during the late phase of disease. Treatment with LTβR-Ig ablated follicular dendritic cell networks in the draining lymph nodes, suggesting that impaired class switching and affinity maturation may have led to a decreased level of pathological autoantibodies. These data are consistent with a model in which the LT/LIGHT axis controls microenvironments in the draining lymph nodes. These environments are critical in shaping the adjuvant-driven initiating events that impact the subsequent quality of the anti-collagen response in the later phases. Consequently, blockade of the LT/LIGHT axis may represent a novel approach to the treatment of autoimmune diseases such as rheumatoid arthritis that involve both T cell and Ab components.

Quick games, puzzles, activities, or instructional strategies are accompanied by suggestions for how an idea can be used by teachers of different grade bands (K–1, 2–3, 4–6). This month's suggestion is to leave the numbers out of a word problem to move students from responding with quick solutions to deeply examining the problem's context.

The intellectual and educational status of 108 children with very low birth weight (≤1,500 g), born from 1965 to 1978, was evaluated and tested on standard tests (eight children with severe handicaps were excluded) at 8 years of age. Fifty-seven were further evaluated at 11 years of age. Six categorical outcomes were defined a priori, based on the Wechsler Intelligence Scale for Children-Revised IQ and discrepancies between Verbal and Performance scores and Bender Gestalt Test score. Proportions at 8 years of age were: 4.6% very low IQ (below 70), 13.9% low IQ (70 to 84), and, for those with IQ greater than 84, 12.0% language disability, 12.0% performance disability, 21.4% visual-motor disability, and 36.1% normal. Learning disabilities, determined by discrepancies between IQ and Wide Range Achievement Test scores, included 16.7% of all children. Outcome proportions at 11 years of age were essentially comparable to those at 8 years of age; outcome constancy was present in 52.6%. Ratings of neonatal illness and parent education level strongly influenced the likelihood of outcome at 8 years of age. When ratings were dichotomized (ie, low v high neonatal illness and low v high parent education), the level of neonatal illness primarily influenced the likelihood of normal outcome, whereas the level of parent education influenced the degree of severity of the disability.

Eighteen- to 60-month-old iron-deficient anemic children given iron therapy (n = 25) and a control group matched for mother's educational level showed no significant difference in mean mental development score at baseline. The control group's mean score was increased significantly over baseline score at 3 and 6 months and was significantly higher than the experimental group's mean score at 3 months. Although the experimental group demonstrated hematologic correction over 6 months, mean mental development score showed no significant improvement. Scores for an iron deficient not anemic group given iron (n = 22), despite complete hematologic correction over the six months of observation, and for its control group, did not change significantly. Baseline scores for an iron-deficient not anemic placebo group (n = 23) and for its control group were not significantly different. At 3 months the control group score had increased significantly, whereas that for the experimental group had not. When experimental and control subjects were matched on baseline mental development score, the control subjects experienced increases in scores over time, further confirming an impaired ability to improve scores with repeated testing in the experimental groups. Behavioral rating data (responsiveness to examiner, responsiveness to environment, and emotional tone) revealed significant differences between the iron-deficient anemic group and its control group at 3 and 6 months, with the control group rated more responsive, suggesting that iron deficiency, alone or in association with anemia, may have some lasting effect on behavior and development. Group differences were also found between the mean number of occurrences of multiple stressful events. Failure to show improvement in scores in the iron-deficient anemic group may reflect the fact that those children were less testable than were children in the control group, despite repeated testings, a theory supported by the infant behavior rating data. This may be related to some irreversible behavioral deficit or to an adverse environmental milieu (e.g., stress).

The infant who is at risk for intellectual impairment because of environmental events in fetal or neonatal life is the special concern of this chapter. Investigators who study the underlying causes of impairment approach the question from varied perspectives. Both medical and social science research will be reviewed here to provide the reader with some synthesis, examine what is known, and consider research methods that offer promise for investigating unresolved questions.

The fetus and neonate may be exposed to a variety of exogenous influences that are potentially damaging to the brain during the time that brain growth and differentiation are most rapid. The major categories of insult are the introduction of neurotoxins into the body, the withholding of essential nutrients, and the disruption of the mechanisms of oxygen and carbon dioxide exchange. These are environmental to the extent that they are caused or controlled by environmental manipulation. At the level of cell metabolism these environmental influences may not be mutually exclusive and may be interdependent. Brain systems undergoing active organization are most vulnerable to damage from adverse conditions such as malnutrition (McKhann et al.,1973) and anoxia (Sumi et al.,1973), suggesting not only that the effects of an insult may be more intense when it is encountered in early life but also that the specific time of encounter may influence the precise nature of these effects.

Washed human platelets were found to enhance phytohemagglutinin (PHA)-stimulated tissue factor (TF) synthesis when incubated with autologous mononuclear cell cultures. Furthermore, platelets increased TF synthesis even when no other stimulator was present during the incubation. Experiments utilizing similar cultures derived from blood of patients with Glanzmann's disease, von Willebrand's disease, and platelet storage pool disease indicated that platelets with each of these genetic defects possessed the capacity to enhance the synthesis of this initiator of coagulation by unstimulated cells as did normal platelets. The degree of platelet enhancement varied between individuals, but for any given donor, the extent of the effect depended on the concentration of platelets used. The effect was demonstrable at platelet/monocyte ratios ranging from a low of approximately 15 to the highest ratio used, about 300. For comparison the ratio of these two cellular elements in normal human blood is estimated to be approximately 1,000. These findings may reflect a relationship between these two cell types that can occur in vivo.

A 66-year-old man with homozygous deficiency of factor VII (less activity than 4 percent of normal) had a minimal hemorrhagic tendency and severe coronary atherosclerosis, and underwent aortocoronary saphenous vein bypass surgery. Although plasma factor VII coagulant activity and cross-reacting material were markedly reduced, comparable amounts of factor VII antigen were detected in peripheral blood mononuclear cells of both the patient and of a normal subject by Western blotting techniques. Accelerated coagulation was observed following brief exposure of the patient's phytohemagglutinin-stimulated peripheral blood mononuclear cells to low concentrations of ambient factor VII in vitro. Evidence indicates that factor VII plays a role in vivo in both hemostasis and atherogenesis and it might be assumed that factor VII deficiency would both predispose to excessive bleeding and forestall atherosclerosis. However, these observations suggest that factor VII-mediated thrombin generation may proceed by partitioning of small amounts of factor VII on tissue factor-expressing cells and that factor VII contained within monocytes may facilitate tissue factor-induced coagulation by these cells. These features may provide efficient coagulation activation despite a deficiency of the plasma coagulant protein. The current results may explain, at least in part, the minimal bleeding tendency, and also the occurrence of thrombosis and atherosclerosis in certain persons with factor VII deficiency.