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OBJECTIVE The aim of this study was to evaluate the utility and safety of "hybrid" stereo-electroencephalography (SEEG) in guiding epilepsy surgery and in providing information at single-neuron levels (i.e., single-unit recording) to further the understanding of the mechanisms of epilepsy and the neurocognitive processes unique to humans. METHODS The authors evaluated 218 consecutive patients undergoing SEEG procedures from 1993 through 2018 at a single academic medical center to assess the utility and safety of this technique in both guiding epilepsy surgery and providing single-unit recordings. The hybrid electrodes used in this study contained macrocontacts and microwires to simultaneously record intracranial EEG and single-unit activity (hybrid SEEG). The outcomes of SEEG-guided surgical interventions were examined, as well as the yield and scientific utility of single-unit recordings in 213 patients who participated in the research involving single-unit recordings. RESULTS All patients underwent SEEG implantation by a single surgeon and subsequent video-EEG monitoring (mean of 10.2 electrodes per patient and 12.0 monitored days). Epilepsy networks were localized in 191 (87.6%) patients. Two clinically significant procedural complications (one hemorrhage and one infection) were noted. Of 130 patients who underwent subsequent focal epilepsy surgery with a minimum 12-month follow-up, 102 (78.5%) underwent resective surgery and 28 (21.5%) underwent closed-loop responsive neurostimulation (RNS) with or without resection. Seizure freedom was achieved in 65 (63.7%) patients in the resective group. In the RNS group, 21 (75.0%) patients achieved 50% or greater seizure reduction. When the initial period of 1993 through 2013 before responsive neurostimulator implantation in 2014 was compared with the subsequent period of 2014 through 2018, the proportion of SEEG patients undergoing focal epilepsy surgery grew from 57.9% to 79.7% due to the advent of RNS, despite a decline in focal resective surgery from 55.3% to 35.6%. A total of 18,680 microwires were implanted in 213 patients, resulting in numerous significant scientific findings. Recent recordings from 35 patients showed a yield of 1813 neurons, with a mean yield of 51.8 neurons per patient. CONCLUSIONS Hybrid SEEG enables safe and effective localization of epileptogenic zones to guide epilepsy surgery and provides unique scientific opportunities to investigate neurons from various brain regions in conscious patients. This technique will be increasingly utilized due to the advent of RNS and may prove a useful approach to probe neuronal networks in other brain disorders.

Since life took its earliest footholds, organisms have been in a perpetual arms race. Evolutionary trial and error has produced increasingly complex organisms. All with a single purpose, to utilize available resources as efficiently as possible and reproduce. This progression has led to things like photosynthesis and respiration, phagocytosis, multicellularity, differentiated cell types, neural networks, and apparently consciousness. This dissertation presents one account of the history of the push-and-pull relationship between life and the environment as both evolved together, centered around two case studies that contributed to the knowledgebase on which the larger argument is founded.Because the net outcome of biological activity is the concentration of reduced material, the net outcome is also environmental oxidation, so long as some of that material still exists. Oxygenic photosynthesis was not necessarily the path of least resistance to ecological success, but once the machinery was assembled, the substrates were nearly limitless in many environments. This intuitively leads to the utilization of O2 in respiration—is by far the best candidate for the job, assuming it is ambiently present. That statement suggests implicitly that evolution will continually exploit its environment to gain a competitive advantage. This effectively frames one side of a long-standing debate concerning the role that environmental O2 concentrations played the evolution of the eukaryotic clade. The chapters herein elaborate on this argument. It begins with a case study of the 1.4-billion-year-old Xiamaling Formation, presenting iron speciation, sulfur isotope, trace metal, and molybdenum isotope data; concluding that while the Xiamaling Formation was likely deposited in a restricted setting, it still holds geochemical indications that global oceans could have been more well oxygenated at the time than many previously thought. The middle chapters explore these ideas further. The dissertation closes with another case study, Meiklejohn Peak. This study presents paired carbon isotope, sulfur isotope, and iodine concentration data, along with detailed sedimentology. The formation explored in this chapter was deposited during one of the largest pulses of diversification in the history of animal life, and multiple independent geochemical proxies suggest rising environmental O2 concentrations accompanied this event.

Nature employs protein aggregates when strong materials are needed to adhere surfaces in extreme environments, allowing organisms to survive conditions ranging from harsh intertidal coasts to open oceans. Amyloids and...

Carcinoma of Unknown Primary presenting primarily as hepatic metastases encompasses a dismal subgroup of tumors with a median survival of 5.9 months. Adenocarcinoma is the most common histological subtype identified upon biopsy and the primary tumor remains undetectable in the majority of cases despite extensive workup. It is important to have a validated and standardized algorithm to follow these tumors to avoid unnecessary tests, as the wishes and health status of the patient represent the principal concerns. The purpose of this paper is to briefly review the current literature on carcinoma of unknown primary with hepatic metastases and propose a standardized diagnostic approach.

The poultry industry in Tanzania has grown steadily over the past decade. We surveyed 121 chicken farming households along an intensification gradient from backyard to semi-intensive and intensive production systems based on rearing system and assumed purpose and poultry breed in the Iringa region. About 30% of households had more than one breed and/or rearing system combination. The subdivision of poultry systems was refined by adding the size of the flocks to highlight variation in scale of operations. On this basis we distinguished 3 main types: 1) subsistence small-scale free-range chicken production; 2) market-oriented small to medium scale semi-intensive and 3) small to medium-large scale intensive systems. ‘Intensification’ involves the transition from keeping indigenous chickens to improved dual-purpose and exotic breeds driven by greater productivity and potential for income generation. The more intensive the production system, the more the intensity and diversity of diseases identified by farmers as their main problem, which was partly attributed to the greater sensitivity of the improved breeds, poor veterinary measures, and the high chicken density facilitating disease spread. Based on the survey we constructed a problem tree to classify the underlying constraints and their interrelations, and to identify common root causes, based on which we propose practical solutions to improve chicken production. Development of medium-large scale systems is particularly constrained by a limited supply of 1-day-old chicks and theft. By contrast, intensification of small-scale systems is constrained by limited access to quality feed, vaccines and medicines, capital, and lack of a reliable market, partly due to the absence of farmer organization. These constraints can be addressed through formation of producer groups and promotion of outgrower and enterprise development models. Enterprise development appears to be the most promising business model for smallholder chicken farmers given that it allows farmers more freedom in decision-making and management while strengthening linkages with input suppliers and output markets to ensure a viable and profitable business.

Building effective state institutions before introducing democracy is widely presumed to improve different development outcomes. Conversely, proponents of this “stateness-first” argument anticipate that democratization before state building yields poor development outcomes. In this Element, we discuss several strong assumptions that (different versions of) this argument rests upon and critically evaluate the existing evidence base. In extension, we specify various observable implications. We then subject the stateness-first argument to multiple tests, focusing on economic growth as an outcome. First, we conduct historical case studies of two countries with different institutional sequencing histories, Denmark and Greece, and assess the stateness-first argument (e.g., by using a synthetic control approach). Thereafter, we draw on an extensive global sample of about 180 countries, measured across 1789–2019 and leverage panel regressions, preparametric matching, and sequence analysis to test a number of observable implications. Overall, we find little evidence to support the stateness-first argument.

Although scholars agree that ethnically divided societies are generally more prone to political violence, critics of consociationalism suggest that proportional representation and parliamentarism provide poor solutions for ethnically heterogeneous settings. I argue that extant findings about the impacts of powersharing institutions on conflict likelihood assume that institutions have a linear relationship with ethnic diversity, whereas in reality, the relationship is more complex. I demonstrate that proportional representation and parliamentarism are associated with an increased likelihood of civil conflict at mid-range levels of diversity but are associated with a decreased risk of conflict in more extremely divided settings, while federalism is independently associated with greater conflict risk at higher levels of ethnic heterogeneity. The results underscore that the peace-promoting effects of institutions may depend on how polarized societies are, encouraging scholars to think more seriously about the effectiveness of consociationalism for mitigating violence where there is greater ethnic diversity.

In research on authoritarian institutions, legislatures are portrayed as capable of resolving dilemmas between the leader and opposition members. Nevertheless, repeated interactions between a leader and their ruling coalition can lead to both contested dictatorships, in which institutions constrain the leader, and established dictatorships, in which the leader exercises near-complete control. To date, however, no one has examined the patterns by which powers vary across legislatures in different settings and over time. Using data from the Varieties of Democracy Project on legislative powers between 1900 and 2017, we conceptualize changes in the powers afforded to the national congress to characterize the development of regimes in either direction. The study expounds on the content of legislatures across regimes and the ways in which they change, encouraging scholars to further consider the relationship between regime dynamics and legislative institutionalization.