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In recent decades, popular sovereignty has come under increasing pressure. The rise of populism, often illiberal or authoritarian, has undermined minority rights, individual autonomy, and rule of law. The expansion of international institutions and greater reliance on market and non-governmental organizations have gradually insulated large areas of policymaking from public control. In turn, these developments cast doubt on the viability and desirability of liberal democracy itself. When the People Rule argues that comprehending and responding to the political crises of our time requires a radical refocusing on popular sovereignty. Each chapter offers a fresh perspective and opens new avenues of inquiry into popular sovereignty, advancing debate over the very heart of this principle - what it means for the people to rule. Thorough and timely, this volume is also available as Open Access on Cambridge Core.
Thirty years after the discovery of an Early Neolithic timber hall at Balbridie in Scotland was reported in Antiquity, new analysis of the site's archaeobotanical assemblage, featuring 20 000 cereal grains preserved when the building burnt down in the early fourth millennium BC, provide new insights into early farming practices. The results of stable isotope analyses of cereals from Balbridie, alongside archaeobotanical and stable isotope results from three other sites, indicate that while cereals were successfully cultivated in well-established plots without manuring at Balbridie, a variety of manuring strategies was implemented at the other sites. These differences reinforce the picture of variability in cultivation practices across Neolithic North-west Europe.
This paper demonstrates experimentally that imposed periodic forcing can significantly alter the global flow characteristics of the flow over a double backward-facing step. The geometry consists of two equal height steps spaced up to eight step heights apart. A periodic zero-mass flux jet located at the first step's top corner was issued at frequencies ranging from below the step-mode instability frequency up to approximately five times the shear-layer instability frequency. Reattachment of the flow onto the first step was achieved for step separations as low as three single-step heights with imposed forcing; significantly shorter than the five single-step heights that occurred without forcing. A significant reduction in mean base pressure on the first step, and increase on the second step, occurred for low forcing frequencies. Even for large step separations, the effect of forcing on the flow persisted sufficiently far downstream to appreciably influence the development of the second recirculation zone. Importantly, previous forced single and unforced double backward-facing step flows provide reference cases to examine and discuss similarities and differences. This study offers insight into possibilities and potential outcomes of flow control for applications ranging from the drag reduction of ground vehicles such as pickup trucks, to enhanced mixing in industrial processes.
This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.
To identify important risk factors for carbapenem-resistant Enterobacterales (CRE) infections among hospitalized patients.
We utilized a case–case–control design that compared patients with CRE infections to patients with carbapenem-susceptible Enterobacterales (CSE) infections and randomly selected controls during the period from January 2011 through December 2016.
The study population was selected from patients at a large metropolitan tertiary-care and instructional medical center.
Cases of CRE were defined as initial admission of adults diagnosed with a bacterial infection of an Enterobacterales species resistant clinically or through sensitivity testing to carbapenems 48 hours or more after admission. Cases of CSE were selected from the same patient population as the CRE cases within a 30-day window for admission, with diagnostic pathogens identified as susceptible to carbapenems. Controls were defined as adult patients admitted to any service within a 30-day window from a CRE case for >48 hours who did not meet either of the above case definitions during that admission.
Antibiotic exposure within 90 days prior to admission and length of hospital stay were both associated with increased odds of CRE and CSE infections compared to controls. Patients with CRE infections had >18 times greater odds of prior antibiotic exposure compared to patients with CSE infections.
Antibiotic exposure and increased length of hospital stay may result in increased patient risk of developing an infection resistant to carbapenems and other β-lactams.
Childbirth may be a traumatic experience and vulnerability to posttraumatic stress disorder (PTSD) may increase the risk of postpartum depression (PPD). We investigated whether genetic vulnerability to PTSD as measured by polygenic score (PGS) increases the risk of PPD and whether a predisposition to PTSD in PPD cases exceeds that of major depressive disorder (MDD) outside the postpartum period.
This case-control study included participants from the iPSYCH2015, a case-cohort of all singletons born in Denmark between 1981 and 2008. Restricting to women born between 1981 and 1997 and excluding women with a first diagnosis other than depression (N = 22 613), 333 were identified with PPD. For each PPD case, 999 representing the background population and 993 with MDD outside the postpartum were matched by calendar year at birth, cohort selection, and age. PTSD PGS was calculated from summary statistics from the Psychiatric Genomics Consortium with LDpred2-auto. Odds ratios (ORs) were estimated using conditional logistic regression adjusted for parental psychiatric history and country of origin, PGS for MDD and age at first birth, and the first 10 principal components.
The PTSD PGS was significantly associated with PPD (OR 1.42, 95% CI 1.20–1.68 per standard deviation increase in PTSD PGS) compared to healthy female controls. Genetic PTSD vulnerability in PPD cases did not exceed that of matched female depression cases outside the postpartum period (OR 1.10, 95% CI 0.94–1.30 per standard deviation increase).
Genetic vulnerability to PTSD increased the risk of PPD but did not differ between PPD cases and women with depression at other times.
The COVID-19 pandemic resulted in millions of deaths worldwide and is considered a significant mass-casualty disaster (MCD). The surge of patients and scarcity of resources negatively impacted hospitals, patients and medical practice. We hypothesized ICUs during this MCD had a higher acuity of illness, and subsequently had increased lengths of stay (LOS), complication rates, death rates and costs of care. The purpose of this study was to investigate those outcomes.
This was a multicenter, retrospective study that compared intensive care admissions in 2020 to those in 2019 to evaluate patient outcomes and cost of care. Data were obtained from the Vizient Clinical Data Base/Resource Manager (Vizient Inc., Irvine, Texas, USA).
Data included the number of ICU admissions, patient outcomes, case mix index and summary of cost reports. Quality outcomes were also collected, and a total of 1304981 patients from 333 hospitals were included. For all medical centers, there was a significant increase in LOS index, ICU LOS, complication rate, case mix index, total cost, and direct cost index.
The MCD caused by COVID-19 was associated with increased adverse outcomes and cost-of-care for ICU patients.
The Homa Peninsula has been known to science since 1911, and fossil specimens from the area comprise many type specimens for common African mammalian paleospecies. Here we discuss the fauna and the paleoenvironmental information from the Homa Peninsula. The Homa Peninsula is a 200 km2 area in Homa Bay County, situated on the southern margin of the Winam Gulf of Lake Victoria in Kenya (Figure 29.1). Lake Victoria is estimated to be the third largest lake in the world, with a surface area of 68,900 km2 and a maximum length of approximately 616 km. Although its catchment is extensive, it is relatively shallow compared to any other lake of similar size, with a maximum depth of 84 m. Lake Victoria is located in a depression formed by the western and eastern branches of the East African Rift System (EARS), and is at an average elevation of 1135 m a.s.l. (Database for Hydrological Time Series of Inland Waters, 2017).
The dating of pollen grains is emerging as the method of choice for lacustrine climate archives that contain few datable macrofossils. Due to the need for high-purity pollen concentrates, new methods are constantly being developed to precisely separate pollen grains. Flow cytometry represents a promising alternative to conventional approaches, enabling the identification of pollen grains through fluorescence and rapid separation for radiocarbon analysis using accelerator mass spectrometry, which has so far been limited to sediments with a high proportion of conifer pollen. We present a revised method for processing large sediment samples, resulting in high-purity pollen and spore concentrates. Using this approach small- to medium-sized pollen and bryophyte spores were isolated from Lake Van sediment samples (Eastern Anatolia, Turkey) in sufficient purity for radiocarbon dating. However, a systematic age discrepancy between pollen and bryophyte spore concentrates was noted. By adapting the chemical and cytometric methods, pure pollen concentrates can be created for sediments with low organic content enabling age determination of climate archives with a low proportion of large pollen or low pollen concentration.
The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.
Background: Povidone-iodine and chlorhexidine gluconate are commonly used antiseptics that have broad antiviral properties, including against SARS-CoV-2. Nasal and oral antisepsis is a possible option to reduce viral transmission; however, effectiveness data are limited. The acceptability of this method for adjunct infection control is also unknown. We are conducting a clinical randomized controlled trial (NCT04478019) to evaluate the effectiveness and feasibility of nasal and oral antisepsis to prevent COVID-19. Methods: Healthcare and other essential workers with in-person job duties were recruited into a 10-week clinical trial. Participation did not require in-person activities: all communication was web- or telephone-based, supplies were shipped directly to the participant, and participants self-collected specimens. Participants completed a 3-week intervention and 3-week control phases and were randomized to the timing of these phases (Fig. 1). During the 3-week intervention phase, participants applied povidone-iodine nasal swabs 2 times per day and chlorhexidine gluconate oral rinse 4 times per day following the manufacturers’ instructions for use. Participants continued all usual infection control measures (eg, face masks, eye protection, gowns, hand hygiene) as required by their workplace. To measure effectiveness against viral transmission, participants collected midturbinate nasal swabs 3 times per week to measure SARS-CoV-2 viral load. Participants also self-reported COVID-19 tests they received and why (eg, symptoms or exposure). To assess acceptability, participants completed pre- and post-surveys about their perceived and actual experience with the interventions. Participants also self-reported adverse effects due to the intervention. Results: As of December 3, 2021, 221 participants (148 healthcare workers and 73 non–healthcare essential workers) had enrolled. Moreover, 20 adverse effects have been reported, including skin irritation, epistaxis, and mouth discoloration; 9 participants withdrew due to side effects. Laboratory analyses are ongoing to measure effectiveness in reducing SARS-CoV-2 viral load. We performed an interim analysis of intervention acceptability. Survey responses were given on a Likert scale of 1 (not at all) to 5 (extremely). Although 36% of respondents (n = 74) reported on the postsurvey that the intervention was less acceptable than they had expected on the presurvey, the overall acceptability measure was still relatively high (3.76) (Fig. 2). In addition, 76% of respondents reported that they would use the intervention in the future (n = 56). Conclusions: Participant recruitment is ongoing, and data continue to be collected to analyze effectiveness and feasibility. Preliminary data suggest that participants find the nasal and oral antisepsis intervention to be an acceptable option to complement standard infection control methods to prevent COVID-19.
Funding: Professional Disposables International, Healthcare Division (PDIHC)
Background: The estimated economic cost of Clostridioides difficile infection (CDI) is $5.4 billion annually, primarily attributed to acute-care costs. We previously reported data from ECOSPOR III that SER-109, an investigational oral microbiome therapeutic, was superior to placebo in reducing recurrent CDI (rCDI) in adults at 8 weeks after treatment, with a 68% relative risk reduction. Adults with rCDI have more hospitalizations and emergency room (ER) visits (defined herein as healthcare resource utilization, HRU) compared to those without recurrence. Thus, we evaluated incidence of HRU. Methods: Adults with rCDI (≥3 episodes in 12 months) were screened at 56 US and Canadian sites and were randomized 1:1 to SER-109 (4 capsules × 3 days) or placebo following resolution of CDI with standard-of-care CDI antibiotics. The primary end point was rCDI at 8 weeks. Exploratory end points included cumulative incidence of hospitalizations through 24 weeks after treatment. Here, we report cumulative incidence of all-cause HRU through 8 weeks after treatment. Results: In total, 281 patients were screened and 182 were randomized (59.9% female; mean age 65.5 years; 98.9% outpatient). Overall, 31 patients (17%) had 38 hospitalizations or ER visits through week 8 (11 events in 10 SER-109 patients and 27 events in 21 placebo patients) (Table 1). The cumulative incidence of HRU was lower in SER-109–treated patients compared to placebo at both weeks 4 and 8 with most events (65.8%) recorded within 4 weeks after treatment. The adjusted HRU incidence rate (by person time, age, sex, and antibiotic use) was also lower in SER-109–treated patients compared to placebo at weeks 4 and 8 (0.256 [95% CI, 0.096–0.683] versus 0.417 [95% CI, 0.199–0.873], respectively). Conclusions: SER-109–treated patients had less HRU compared to placebo patients through 8 weeks after treatment in this mostly outpatient population. These data suggest a potential benefit of SER-109 in reducing HRU, thus lowering the healthcare burden of rCDI.
Automated virtual reality therapies are being developed to increase access to psychological interventions. We assessed the experience with one such therapy of patients diagnosed with psychosis, including satisfaction, side effects, and positive experiences of access to the technology. We tested whether side effects affected therapy.
In a clinical trial 122 patients diagnosed with psychosis completed baseline measures of psychiatric symptoms, received gameChange VR therapy, and then completed a satisfaction questionnaire, the Oxford-VR Side Effects Checklist, and outcome measures.
79 (65.8%) patients were very satisfied with VR therapy, 37 (30.8%) were mostly satisfied, 3 (2.5%) were indifferent/mildly dissatisfied, and 1 (0.8%) person was quite dissatisfied. The most common side effects were: difficulties concentrating because of thinking about what might be happening in the room (n = 17, 14.2%); lasting headache (n = 10, 8.3%); and the headset causing feelings of panic (n = 9, 7.4%). Side effects formed three factors: difficulties concentrating when wearing a headset, feelings of panic using VR, and worries following VR. The occurrence of side effects was not associated with number of VR sessions, therapy outcomes, or psychiatric symptoms. Difficulties concentrating in VR were associated with slightly lower satisfaction. VR therapy provision and engagement made patients feel: proud (n = 99, 81.8%); valued (n = 97, 80.2%); and optimistic (n = 96, 79.3%).
Patients with psychosis were generally very positive towards the VR therapy, valued having the opportunity to try the technology, and experienced few adverse effects. Side effects did not significantly impact VR therapy. Patient experience of VR is likely to facilitate widespread adoption.
Disruptive behavior disorders (DBD) are heterogeneous at the clinical and the biological level. Therefore, the aims were to dissect the heterogeneous neurodevelopmental deviations of the affective brain circuitry and provide an integration of these differences across modalities.
We combined two novel approaches. First, normative modeling to map deviations from the typical age-related pattern at the level of the individual of (i) activity during emotion matching and (ii) of anatomical images derived from DBD cases (n = 77) and controls (n = 52) aged 8–18 years from the EU-funded Aggressotype and MATRICS consortia. Second, linked independent component analysis to integrate subject-specific deviations from both modalities.
While cases exhibited on average a higher activity than would be expected for their age during face processing in regions such as the amygdala when compared to controls these positive deviations were widespread at the individual level. A multimodal integration of all functional and anatomical deviations explained 23% of the variance in the clinical DBD phenotype. Most notably, the top marker, encompassing the default mode network (DMN) and subcortical regions such as the amygdala and the striatum, was related to aggression across the whole sample.
Overall increased age-related deviations in the amygdala in DBD suggest a maturational delay, which has to be further validated in future studies. Further, the integration of individual deviation patterns from multiple imaging modalities allowed to dissect some of the heterogeneity of DBD and identified the DMN, the striatum and the amygdala as neural signatures that were associated with aggression.
The storming of the US Capitol building in January 2021 was a presidential attempt at a self-coup. To make the case, this article reviews elements of the Capitol assault and the events leading up to it, in light of the key conceptual components of a self-coup, and how those compare to attributes of other kinds of attacks on governments. The Trump self-coup will then be compared and contrasted empirically to other self-coups perpetrated by leaders. It is found that what separates successful self-coups from those that fail is whether the military backs the undertaking. Thus, a section is included on US military behaviour in response to Trump's attempts to gain military adherence for his political actions.