Multidisciplinary surgical considerations for en bloc resection of sacral chordoma: review of recent advances and a contemporary single-center series.

OBJECTIVE: Contemporary management of sacral chordomas requires maximizing the potential for recurrence-free and overall survival while minimizing treatment morbidity. En bloc resection can be performed at various levels of the sacrum, with tumor location and volume ultimately dictating the necessary extent of resection and subsequent tissue reconstruction. Because tumor resection involving the upper sacrum may be quite destabilizing, other pertinent considerations relate to instrumentation and subsequent tissue reconstruction. The primary aim of this study was to survey the surgical approaches used for managing primary sacral chordoma according to location of lumbosacral spine involvement, including a narrative review of the literature and examination of the authors' institutional case series. METHODS: The authors performed a narrative review of pertinent literature regarding reconstruction and complication avoidance techniques following en bloc resection of primary sacral tumors, supplemented by a contemporary series of 11 cases from their cohort. Relevant surgical anatomy, advances in instrumentation and reconstruction techniques, intraoperative imaging and navigation, soft-tissue reconstruction, and wound complication avoidance are also discussed. RESULTS: The review of the literature identified several surgical approaches used for management of primary sacral chordoma localized to low sacral levels (mid-S2 and below), high sacral levels (involving upper S2 and above), and high sacral levels with lumbar involvement. In the contemporary case series, the majority of cases (8/11) presented as low sacral tumors that did not require instrumentation. A minority required more extensive instrumentation and reconstruction, with 2 tumors involving upper S2 and/or S1 levels and 1 tumor extending into the lower lumbar spine. En bloc resection was successfully achieved in 10 of 11 cases, with a colostomy required in 2 cases due to rectal involvement. All 11 cases underwent musculocutaneous flap wound closure by plastic surgery, with none experiencing wound complications requiring revision. CONCLUSIONS: The modern management of sacral chordoma involves a multidisciplinary team of surgeons and intraoperative technologies to minimize surgical morbidity while optimizing oncological outcomes through en bloc resection. Most cases present with lower sacral tumors not requiring instrumentation, but stabilizing instrumentation and lumbosacral reconstruction are often required in upper sacral and lumbosacral cases. Among efforts to minimize wound-related complications, musculocutaneous flap closure stands out as an evidence-based measure that may mitigate risk.

Multimodal decoding of human liver regeneration.

The liver has a unique ability to regenerate1,2; however, in the setting of acute liver failure (ALF), this regenerative capacity is often overwhelmed, leaving emergency liver transplantation as the only curative option3-5. Here, to advance understanding of human liver regeneration, we use paired single-nucleus RNA sequencing combined with spatial profiling of healthy and ALF explant human livers to generate a single-cell, pan-lineage atlas of human liver regeneration. We uncover a novel ANXA2+ migratory hepatocyte subpopulation, which emerges during human liver regeneration, and a corollary subpopulation in a mouse model of acetaminophen (APAP)-induced liver regeneration. Interrogation of necrotic wound closure and hepatocyte proliferation across multiple timepoints following APAP-induced liver injury in mice demonstrates that wound closure precedes hepatocyte proliferation. Four-dimensional intravital imaging of APAP-induced mouse liver injury identifies motile hepatocytes at the edge of the necrotic area, enabling collective migration of the hepatocyte sheet to effect wound closure. Depletion of hepatocyte ANXA2 reduces hepatocyte growth factor-induced human and mouse hepatocyte migration in vitro, and abrogates necrotic wound closure following APAP-induced mouse liver injury. Together, our work dissects unanticipated aspects of liver regeneration, demonstrating an uncoupling of wound closure and hepatocyte proliferation and uncovering a novel migratory hepatocyte subpopulation that mediates wound closure following liver injury. Therapies designed to promote rapid reconstitution of normal hepatic microarchitecture and reparation of the gut-liver barrier may advance new areas of therapeutic discovery in regenerative medicine.

US homicide rates increase when resources are scarce and unequally distributed.

As homicide rates spike across the United States, researchers nominate diverse causes such as temperature, city greenness, structural racism, inequality, poverty and more. While variation in homicide rates clearly results from multiple causes, many correlation studies lack the systematic theory needed to identify the underlying factors that structure individual motivations. Building on pioneering work in evolutionary human sciences, we propose that when resources are unequally distributed, individuals may have incentives to undertake high-risk activities, including lethal violence, in order to secure material and social capital. Here we evaluate this theory by analysing federal data on homicide rates, poverty and income inequality across all 50 US states for the years 1990, 2000 and 2005-2020. Supporting predictions derived from evolutionary social sciences, we find that the interaction of poverty (scarcity) and inequality (unequal distribution) best explains variation in US homicide rates. Results suggest that the increase in homicide rates during the height of the COVID-19 pandemic are driven in part by these same underlying causes that structure homicide rates across the US over the last 30 years. We suggest that these results provide compelling evidence to expand strategies for reducing homicide rates by dismantling structures that generate and concentrate sustained poverty and economic inequality.

Repeat testing of mpox specimens with late CTs improves detection of potential false positive cases.

The mpox pandemic necessitated the rapid development of clinical assays for monkeypox virus detection. While the majority of mpox specimens have high viral loads with corresponding early cycle threshold (CT) values, reports have indicated some specimens with late CT values can represent false positive results. To mitigate this risk, the Centers for Disease Control and Prevention (CDC) published an advisory recommending repeat testing of all specimens with CT values ≥34. However, limited experimental data were available to support this specific cutoff. In this study, we examine whether a more conservative approach in which all specimens with CT values ≥29 are repeated would improve the detection of potential false positive results. Compared to the CDC algorithm, our approach identified an additional 20% (5/25) of potential false positive results. To assess the impact of this cutoff on laboratory workload, we modeled the expected increase in test volume and turnaround time (TAT) relative to the CDC method. Using a lower repeat threshold, test volume increased by 0.7% while mean TAT increased by less than 15 minutes. Overall, a lower threshold than recommended by the CDC for repeating late CT mpox specimens may reduce the number of false positives reported while minimally impacting testing volume and TAT.

Development and validation of a next-generation sequencing assay with open-access analysis software for detecting resistance-associated mutations in CMV.

Cytomegalovirus (CMV) resistance testing by targeted next-generation sequencing (NGS) allows for the simultaneous analysis of multiple genes. We developed and validated an amplicon-based Ion Torrent NGS assay to detect CMV resistance mutations in UL27, UL54, UL56, and UL97 and compared the results to standard Sanger sequencing. NGS primers were designed to generate 83 overlapping amplicons of four CMV genes (~10 kb encompassing 138 mutation sites). An open-access software plugin was developed to perform read alignment, call variants, and interpret drug resistance. Plasmids were tested to determine NGS error rate and minor variant limit of detection. NGS limit of detection was determined using the CMV WHO International Standard and quantified clinical specimens. Reproducibility was also assessed. After establishing quality control metrics, 185 patient specimens previously tested using Sanger were reanalyzed by NGS. The NGS assay had a low error rate (<0.05%) and high accuracy (95%) for detecting CMV-associated resistance mutations present at ≥5% in contrived mixed populations. Mutation sites were reproducibly sequenced with 40× coverage when plasma viral loads were ≥2.6 log IU/mL. NGS detected the same resistance-associated mutations identified by Sanger in 68/69 (98.6%) specimens. In 16 specimens, NGS detected 18 resistance mutations that Sanger failed to detect; 14 were low-frequency variants (<20%), and six would have changed the drug resistance interpretation. The NGS assay showed excellent agreement with Sanger and generated high-quality sequence from low viral load specimens. Additionally, the higher resolution and analytic sensitivity of NGS potentially enables earlier detection of antiviral resistance.

Evaluation of Viral Inactivation on Dry Surface by High Peak Power Microwave (HPPM) Exposure.

Previous research has shown that virus infectivity can be dramatically reduced by radio frequency exposure in the gigahertz (GHz) frequency range. Given the worldwide SARS-CoV-2 pandemic, which has caused over 1 million deaths and has had a profound global economic impact, there is a need for a noninvasive technology that can reduce the transmission of virus among humans. RF is a potential wide area-of-effect viral decontamination technology that could be used in hospital rooms where patients are expelling virus, in grocery and convenience stores where local populations mix, and in first responder settings where rapid medical response spans many potentially infected locations within hours. In this study, we used bovine coronavirus (BCoV) as a surrogate of SARS-CoV-2 and exposed it to high peak power microwave (HPPM) pulses at four narrowband frequencies: 2.8, 5.6, 8.5, and 9.3 GHz. Exposures consisted of 2 µs pulses delivered at 500 Hz, with pulse counts varied by decades between 1 and 10,000. The peak field intensities (i.e. the instantaneous power density of each pulse) ranged between 0.6 and 6.5 MW/m2 , depending on the microwave frequency. The HPPM exposures were delivered to plastic coverslips containing BCoV dried on the surface. Hemagglutination (HA) and cytopathic effect analyses were performed 6 days after inoculation of host cells to assess viral infectivity. No change in viral infectivity was seen with increasing dose (pulse number) across the tested frequencies. Under all conditions tested, exposure did not reduce infectivity more than 1.0 log10. For the conditions studied, high peak power pulsed RF exposures in the 2-10 GHz range appear ineffective as a virucidal approach for hard surface decontamination. © 2023 Bioelectromagnetics Society.

Enantioselective Total Synthesis of (+)-Alterbrassicicene C.

Herein, the first total synthesis of (+)-alterbrassicicene C (2) is described. Key features of the synthesis include an oxiranium mediated ether ring expansion, an oxa-Michael/retro-oxa-Michael cascade, and installation of a vinyl methoxy ether moiety via Stille coupling.

Tolerability and efficacy of duloxetine for the prevention of persistent musculoskeletal pain after trauma and injury: a pilot three-group randomized controlled trial.

ABSTRACT: This study investigated the tolerability and preliminary efficacy of duloxetine as an alternative nonopioid therapeutic option for the prevention of persistent musculoskeletal pain (MSP) among adults presenting to the emergency department with acute MSP after trauma or injury. In this randomized, double-blind, placebo-controlled study, eligible participants (n = 78) were randomized to 2 weeks of a daily dose of one of the following: placebo (n = 27), 30 mg duloxetine (n = 24), or 60 mg duloxetine (n = 27). Tolerability, the primary outcome, was measured by dropout rate and adverse effects. Secondary outcomes assessed drug efficacy as measured by (1) the proportion of participants with moderate to severe pain (numerical rating scale ≥ 4) at 6 weeks (pain persistence); and (2) average pain by group over the six-week study period. We also explored treatment effects by type of trauma (motor vehicle collision [MVC] vs non-MVC). In both intervention groups, duloxetine was well tolerated and there were no serious adverse events. There was a statistically significant difference in pain over time for the 60 mg vs placebo group ( P = 0.03) but not for the 30 mg vs placebo group ( P = 0.51). In both types of analyses, the size of the effect of duloxetine was larger in MVC vs non-MVC injury. Consistent with the role of stress systems in the development of chronic pain after traumatic stress, our data indicate duloxetine may be a treatment option for reducing the transition from acute to persistent MSP. Larger randomized controlled trials are needed to confirm these promising results.

Mathematical modeling of the dynamics of COVID-19 variants of concern: Asymptotic and finite-time perspectives.

The COVID-19 pandemic has seen multiple waves, in part due to the implementation and relaxation of social distancing measures by the public health authorities around the world, and also caused by the emergence of new variants of concern (VOCs) of the SARS-Cov-2 virus. As the COVID-19 pandemic is expected to transition into an endemic state, how to manage outbreaks caused by newly emerging VOCs has become one of the primary public health issues. Using mathematical modeling tools, we investigated the dynamics of VOCs, both in a general theoretical framework and based on observations from public health data of past COVID-19 waves, with the objective of understanding key factors that determine the dominance and coexistence of VOCs. Our results show that the transmissibility advantage of a new VOC is a main factor for it to become dominant. Additionally, our modeling study indicates that the initial number of people infected with the new VOC plays an important role in determining the size of the epidemic. Our results also support the evidence that public health measures targeting the newly emerging VOC taken in the early phase of its spread can limit the size of the epidemic caused by the new VOC (Wu et al., 2139Wu, Scarabel, Majeed, Bragazzi, & Orbinski, ; Wu et al., 2021).

Drought-Induced Civil Conflict Among the Ancient Maya.

The influence of climate change on civil conflict and societal instability in the premodern world is a subject of much debate, in part because of the limited temporal or disciplinary scope of case studies. We present a transdisciplinary case study that combines archeological, historical, and paleoclimate datasets to explore the dynamic, shifting relationships among climate change, civil conflict, and political collapse at Mayapan, the largest Postclassic Maya capital of the Yucatán Peninsula in the thirteenth and fourteenth centuries CE. Multiple data sources indicate that civil conflict increased significantly and generalized linear modeling correlates strife in the city with drought conditions between 1400 and 1450 cal. CE. We argue that prolonged drought escalated rival factional tensions, but subsequent adaptations reveal regional-scale resiliency, ensuring that Maya political and economic structures endured until European contact in the early sixteenth century CE.

HIV-1 Drug Resistance Assay Using Ion Torrent Next Generation Sequencing and On-Instrument End-to-End Analysis Software.

HIV-1 antiretroviral therapy management requires sequencing the protease, reverse transcriptase, and integrase portions of the HIV-1 pol gene. Most resistance testing is performed with Sanger sequencing, which has limited ability to detect minor variants. Next generation sequencing (NGS) platforms enable variant detection at frequencies as low as 1% allowing for earlier detection of resistance and modification of therapy. Implementation of NGS assays in the clinical laboratory is hindered by complicated assay design, cumbersome wet bench procedures, and the complexity of data analysis and bioinformatics. We developed a complete NGS protocol and companion analysis and reporting pipeline using AmpliSeq multiplex PCR, Ion Torrent S5 XL sequencing, and Stanford's HIVdb resistance algorithm. Implemented as a Torrent Suite software plugin, the pipeline runs automatically after sequencing. An optimum variant frequency threshold of 10% was determined by comparing Sanger sequences of archived samples from ViroSeq testing, resulting in a sensitivity of 98.2% and specificity of 99.0%. The majority (91%) of drug resistance mutations were detected by both Sanger and NGS, with 1.7% only by Sanger and 7.3% only by NGS. Variant calls were highly reproducible and there was no cross-reactivity to VZV, HBV, CMV, EBV, and HCV. The limit of detection was 500 copies/mL. The NGS assay performance was comparable to ViroSeq Sanger sequencing and has several advantages, including a publicly available end-to-end analysis and reporting plugin. The assay provides a straightforward path for implementation of NGS for HIV drug resistance testing in the laboratory setting without additional investment in bioinformatics infrastructure and resources.

Subsistence strategy mediates ecological drivers of human violence.

Inter-personal violence (whether intra- or inter-group) is a pervasive yet highly variable human behavior. Evolutionary anthropologists suggest that the abundance and distribution of resources play an important role in influencing differences in rates of violence, with implications for how resource conditions structure adaptive payoffs. Here, we assess whether differences in large-scale ecological conditions explain variability in levels of inter-personal human violence. Model results reveal a significant relationship between resource conditions and violence that is mediated by subsistence economy. Specifically, we find that interpersonal violence is highest: (1) among foragers and mixed forager/farmers (horticulturalists) in productive, homogeneous environments, and (2) among agriculturalists in unproductive, heterogeneous environments. We argue that the trend reversal between foragers and agriculturalists represents differing competitive pathways to enhanced reproductive success. These alternative pathways may be driven by features of subsistence (i.e., surplus, storage, mobility, privatization), in which foragers use violence to directly acquire fitness-linked social payoffs (i.e., status, mating opportunities, alliances), and agriculturalists use violence to acquire material resources that can be transformed into social payoffs. We suggest that as societies transition from immediate return economies (e.g., foragers) to delayed return economies (e.g., agriculturalists) material resources become an increasingly important adaptive payoff for inter-personal, especially inter-group, violence.

Climate change-induced population pressure drives high rates of lethal violence in the Prehispanic central Andes.

Understanding the influence of climate change and population pressure on human conflict remains a critically important topic in the social sciences. Long-term records that evaluate these dynamics across multiple centuries and outside the range of modern climatic variation are especially capable of elucidating the relative effect of­and the interaction between­climate and demography. This is crucial given that climate change may structure population growth and carrying capacity, while both climate and population influence per capita resource availability. This study couples paleoclimatic and demographic data with osteological evaluations of lethal trauma from 149 directly accelerator mass spectrometry 14C-dated individuals from the Nasca highland region of Peru. Multiple local and supraregional precipitation proxies are combined with a summed probability distribution of 149 14C dates to estimate population dynamics during a 700-y study window. Counter to previous findings, our analysis reveals a precipitous increase in violent deaths associated with a period of productive and stable climate, but volatile population dynamics. We conclude that favorable local climate conditions fostered population growth that put pressure on the marginal and highly circumscribed resource base, resulting in violent resource competition that manifested in over 450 y of internecine warfare. These findings help support a general theory of intergroup violence, indicating that relative resource scarcity­whether driven by reduced resource abundance or increased competition­can lead to violence in subsistence societies when the outcome is lower per capita resource availability.

Climate and demography drive 7000 years of dietary change in the Central Andes.

Explaining the factors that influence past dietary variation is critically important for understanding changes in subsistence, health, and status in past societies; yet systematic studies comparing possible driving factors remain scarce. Here we compile the largest dataset of past diet derived from stable isotope δ13C‰ and δ15N‰ values in the Americas to quantitatively evaluate the impact of 7000 years of climatic and demographic change on dietary variation in the Central Andes. Specifically, we couple paleoclimatic data from a general circulation model with estimates of relative past population inferred from archaeologically derived radiocarbon dates to assess the influence of climate and population on spatiotemporal dietary variation using an ensemble machine learning model capable of accounting for interactions among predictors. Results reveal that climate and population strongly predict diet (80% of δ15N‰ and 66% of Î´13C‰) and that Central Andean diets correlate much more strongly with local climatic conditions than regional population size, indicating that the past 7000 years of dietary change was influenced more by climatic than socio-demographic processes. Visually, the temporal pattern suggests decreasing dietary variation across elevation zones during the Late Horizon, raising the possibility that sociopolitical factors overrode the influence of local climatic conditions on diet during that time. The overall findings and approach establish a general framework for understanding the influence of local climate and demography on dietary change across human history.

SNAPSHOT USA 2019: a coordinated national camera trap survey of the United States.

With the accelerating pace of global change, it is imperative that we obtain rapid inventories of the status and distribution of wildlife for ecological inferences and conservation planning. To address this challenge, we launched the SNAPSHOT USA project, a collaborative survey of terrestrial wildlife populations using camera traps across the United States. For our first annual survey, we compiled data across all 50 states during a 14-week period (17 August-24 November of 2019). We sampled wildlife at 1,509 camera trap sites from 110 camera trap arrays covering 12 different ecoregions across four development zones. This effort resulted in 166,036 unique detections of 83 species of mammals and 17 species of birds. All images were processed through the Smithsonian's eMammal camera trap data repository and included an expert review phase to ensure taxonomic accuracy of data, resulting in each picture being reviewed at least twice. The results represent a timely and standardized camera trap survey of the United States. All of the 2019 survey data are made available herein. We are currently repeating surveys in fall 2020, opening up the opportunity to other institutions and cooperators to expand coverage of all the urban-wild gradients and ecophysiographic regions of the country. Future data will be available as the database is updated at eMammal.si.edu/snapshot-usa, as will future data paper submissions. These data will be useful for local and macroecological research including the examination of community assembly, effects of environmental and anthropogenic landscape variables, effects of fragmentation and extinction debt dynamics, as well as species-specific population dynamics and conservation action plans. There are no copyright restrictions; please cite this paper when using the data for publication.

Using a multimethod life history approach to navigate the osteological paradox: A case study from Prehispanic Nasca, Peru.

OBJECTIVES: We leverage recent bioarchaeological approaches and life history theory to address the implications of the osteological paradox in a study population. The goal of this article is to evaluate morbidity and mortality patterns as well as variability in the risk of disease and death during the Late Intermediate period (LIP; 950-1450 C.E.) in the Nasca highlands of Peru. We demonstrate how the concurrent use of multiple analytical techniques and life history theory can engage the osteological paradox and provide salient insights into the study of stress, frailty, and resilience in past populations. MATERIALS AND METHODS: Crania from LIP burial contexts in the Nasca highlands were examined for cribra orbitalia (n = 325) and porotic hyperostosis (n = 270). All age groups and both sexes are represented in the sample. Survivor/nonsurvivor analysis assessed demographic differences in lesion frequency and severity. Hazard models were generated to assess differences in survivorship. The relationship between dietary diversity and heterogeneity in morbidity was assessed using stable δ15 N and δ13 C isotope values for bone collagen and carbonate. One hundred and twenty-four crania were directly AMS radiocarbon dated, allowing for a diachronic analysis of morbidity and mortality. RESULTS: The frequency and expression of both orbital and vault lesions increases significantly during the LIP. Survivor/nonsurvivor analysis indicates cranial lesions co-vary with frailty rather than robusticity or longevity. Hazard models show (1) decreasing survivorship with the transition into the LIP, (2) significantly lower adult life expectancy for females compared to males, and (3) individuals with cranial lesions have lower survivorship across the life course. Stable isotope results show very little dietary diversity. Mortality risk and frequency of pathological skeletal lesions were highest during Phase III (1300-1450 C.E.) of the LIP. CONCLUSION: Results provide compelling evidence of increasing physiological stress and mortality in the Nasca highlands during the LIP, but also reveal substantial heterogeneity in frailty and the risk of death. Certain members of society experienced a heavier disease burden and higher mortality compared to their contemporaries. Elevated levels of disease and lethal trauma among females account for some of the sex differences in survivorship but cannot explain the large degree of female-biased mortality. We hypothesize that parental investment in males or increased female fertility rates may explain these differences.

Modeling the Effects of Latency Reversing Drugs During HIV-1 and SIV Brain Infection with Implications for the "Shock and Kill" Strategy.

Combination antiretroviral therapy (cART) has greatly increased life expectancy for human immunodeficiency virus-1 (HIV-1)-infected patients. Even given the remarkable success of cART, the virus persists in many different cells and tissues. The presence of viral reservoirs represents a major obstacle to HIV-1 eradication. These viral reservoirs contain latently infected long-lived cells. The "Shock and Kill" therapeutic strategy aims to reactivate latently infected cells by latency reversing agents (LRAs) and kill these reactivated cells by strategies involving the host immune system. The brain is a natural anatomical reservoir for HIV-1 infection. Brain macrophages, including microglia and perivascular macrophages, display productive HIV-1 infection. A mathematical model was used to analyze the dynamics of latently and productively infected brain macrophages during viral infection and this mathematical model enabled prediction of the effects of LRAs applied to the "Shock and Kill" strategy in the brain. The model was calibrated using reported data from simian immunodeficiency virus (SIV) studies. Our model produces the overarching observation that effective cART can suppress productively infected brain macrophages but leaves a residual latent viral reservoir in brain macrophages. In addition, our model demonstrates that there exists a parameter regime wherein the "Shock and Kill" strategy can be safe and effective for SIV infection in the brain. The results indicate that the "Shock and Kill" strategy can restrict brain viral RNA burden associated with severe neuroinflammation and can lead to the eradication of the latent reservoir of brain macrophages.

A genetic history of the pre-contact Caribbean.

Humans settled the Caribbean about 6,000 years ago, and ceramic use and intensified agriculture mark a shift from the Archaic to the Ceramic Age at around 2,500 years ago1-3. Here we report genome-wide data from 174 ancient individuals from The Bahamas, Haiti and the Dominican Republic (collectively, Hispaniola), Puerto Rico, Curaçao and Venezuela, which we co-analysed with 89 previously published ancient individuals. Stone-tool-using Caribbean people, who first entered the Caribbean during the Archaic Age, derive from a deeply divergent population that is closest to Central and northern South American individuals; contrary to previous work4, we find no support for ancestry contributed by a population related to North American individuals. Archaic-related lineages were >98% replaced by a genetically homogeneous ceramic-using population related to speakers of languages in the Arawak family from northeast South America; these people moved through the Lesser Antilles and into the Greater Antilles at least 1,700 years ago, introducing ancestry that is still present. Ancient Caribbean people avoided close kin unions despite limited mate pools that reflect small effective population sizes, which we estimate to be a minimum of 500-1,500 and a maximum of 1,530-8,150 individuals on the combined islands of Puerto Rico and Hispaniola in the dozens of generations before the individuals who we analysed lived. Census sizes are unlikely to be more than tenfold larger than effective population sizes, so previous pan-Caribbean estimates of hundreds of thousands of people are too large5,6. Confirming a small and interconnected Ceramic Age population7, we detect 19 pairs of cross-island cousins, close relatives buried around 75 km apart in Hispaniola and low genetic differentiation across islands. Genetic continuity across transitions in pottery styles reveals that cultural changes during the Ceramic Age were not driven by migration of genetically differentiated groups from the mainland, but instead reflected interactions within an interconnected Caribbean world1,8.

The character of conflict: A bioarchaeological study of violence in the Nasca highlands of Peru during the Late Intermediate Period (950-1450 C.E.).

OBJECTIVES: This study uses osteological and radiocarbon datasets combined with formal quantitative analyses to test hypotheses concerning the character of conflict in the Nasca highlands during the Late Intermediate Period (LIP, 950-1450 C.E.). We develop and test osteological expectations regarding what patterns should be observed if violence was characterized by intragroup violence, ritual conflict, intermittent raiding, or internecine warfare. MATERIALS AND METHODS: Crania (n = 267) were examined for antemortem and perimortem, overkill, and critical trauma. All age groups and both sexes are represented in the sample. One hundred twenty-four crania were AMS dated, allowing a detailed analysis of diachronic patterns in violence among various demographic groups. RESULTS: Thirty-eight percent (102/267) of crania exhibit some form of cranial trauma, a significant increase from the preceding Middle Horizon era. There are distinct trauma frequencies within the three subphases of the LIP, but Phase III (1300-1450 C.E.) exhibits the highest frequencies of all trauma types. Males exhibit significantly more antemortem trauma than females, but both exhibit similar perimortem trauma rates. DISCUSSION: There was chronic, internecine warfare throughout the Late Intermediate Period with important variations in violence throughout the three temporal phases. Evidence for heterogeneity in violent mortality shows a pattern consistent with social substitutability, whereby any and all members of the Nasca highland population were appropriate targets for lethal and sublethal violence. We argue that by testing hypotheses regarding the targets and types of conflict we are better able to explain the causes and consequences of human conflict.

Utilization of the Thorpe-Ingold Effect in the Synthesis of Cyclooctanoid Ring Systems via Anionic 6-exo-dig Cyclization/Claisen Rearrangement Sequence.

We demonstrate a facile approach for the synthesis of gem-disubstituted cyclooctanoids, a motif found in several biologically active compounds. Appropriately substituted 1-alkenyl-5-pentyn-1-ols bearing gem-dialkyl substituents at either the C2, C3, or C4 position serve as useful precursors to a number of cyclooct-4-enone derivatives via a tandem, microwave-assisted oxyanionic 6-exo-dig cyclization/Claisen rearrangement reaction. gem-Dialkyl activation is necessary for these reactions to occur, as unactivated 1-alkenyl-5-pentyn-1-ols fail to undergo 6-exo-dig cyclization under the conditions employed. Further application of the methodology to the corresponding gem-dialkoxy system was also explored to facilitate access to more complex carbocycles.