bluuebunny/crossref_metadata_2025 huggingface dataset:
The Indian Princely States and Their Rulers
Authors: Jhala Angma D.
Published: October 2019

Colonial South Asian history has focused on British India and the nationalists who later resisted and supplanted it. However, long before India’s independence from Britain, there were regions where neither the British nor the nationalists were primarily positioned. These were the approximately six hundred semi-autonomous kingdoms, or “princely states” (often referred to as “Indian India”), which spanned the breadth and length of the subcontinent. They comprised two-fifths of the landmass and one-third of the population, excluding Burma. Though their rulers were long marginalized in modern South Asian and imperial history as antiquated relics of the medieval era, oriental despots, or puppet princes, they were real forces in the governing of the subcontinent, not only during the precolonial era but also at the heyday of the British Empire and continue to play a part in modern South Asia. Native rulers introduced new systems of administration, taxation, law, religious and social reform, trade, education, public health, and technology, including railways, ginning factories, and telegraphs, to their states; served as patrons of architecture, the arts, culinary innovation, and sport; encouraged the introduction of representative forms of government; and, in certain cases, supported popular anticolonial movements. In some principalities, where ruling families practiced different faiths from the majority of their citizens, their policies would influence the political trajectories of their erstwhile states long after the end of colonialism. With India’s independence and Partition in 1947, the princely states merged with the new nations of South Asia, and in the 1970s former princes lost their economic entitlement of the Privy Purse. However, they continued to play a part in postcolonial South Asia, serving as diplomats, governors, patrons of educational and charitable institutions, local magnates, company directors, cabinet ministers and, perhaps most prominently, as elected politicians and leaders of heritage tourism.
Reproductive Health, Fertility Control, and Childbirth in Africa
Authors: Klausen Susanne M.
Published: October 2019

Fertility has long been highly prized in Africa, especially in societies where economic production depended mainly on human labor power. In addition to their role as future workers, children were crucial for, inter alia, securing lineages, providing social security, and ensuring spiritual safekeeping. Women were therefore expected to produce offspring. For them, bearing children was elemental to their social identity, security, and status; failing to reproduce could be calamitous. For both women and their husbands, infertility was often stigmatizing, but women usually bore the brunt of blame for involuntary childlessness and therefore could suffer especially devastating social consequences, such as divorce and ostracism. Managing fertility involved a wide range of reproductive practices. Africans believed infertility was caused by supernatural forces; consequently they sought assistance from spirit mediums and traditional healers to help women achieve or maintain fecundity. Postpartum women practiced birth spacing to ensure infants’ health, achieved through sexual abstinence and prolonged breastfeeding. Because premarital pregnancy was often a serious violation of social norms, youth were typically taught ways to avoid conception while engaging in premarital sex play. Women procured abortions using a variety of methods, including ingestion of plant-based concoctions and extreme manual pressure to kill the fetus. Childbirth, though feared for the risk involved, was typically a welcomed event although the social context for birth varied according to culture and social organization. In some societies, midwives attended women, whereas in others, solitary birth was the ideal. The reproductive politics and practices of precolonial societies informed those of the colonial era, which in turn helped shape postcolonial Africa. Western incursions into African societies had uneven effects on indigenous practices related to reproductive health, fertility control, and childbirth. While some indigenous ideas and practices persist, others, such as post-partum sexual abstinence, have been severely undermined.
The Legal and Political Framework for Archaeology and the Protection of Archaeological Resources in South Africa
Authors: Deacon Janette
Published: October 2019

It is no surprise that the legal framework that protects archaeological and other heritage resources in South Africa is firmly rooted in the country’s political history and latterly in internationally accepted guidelines. The British colonial system that was applied in many African colonies in the 20th century, for example Zimbabwe (Southern Rhodesia), Botswana (Bechuanaland), and Tanzania (Tanganyika), shaped the early legislation and, until the new millennium, was essentially reactive. Western-style government was firmly in charge, traditional managers were not consulted, and legal action could be taken (but seldom was) against those who ignored the protective measures and damaged the archaeological material or site. In South Africa, the National Heritage Resources Act (Act 25 of 1999), which was implemented by the new democratically elected government in 2000, six years after the fall of apartheid, broadened the range of definitions to identify mainly historical places of significance that had not been recorded before, such as sites of slavery and graves of victims of political conflict. Proactive measures were introduced to assess the impact of development on archaeological sites and their mitigation before development, and the assessment process guides management strategies to retain the significance. Some of these reforms were borrowed from legislation in former British colonies such as Australia, New Zealand, and Canada, and the framework was influenced by international guidelines such as the Burra Charter and the Operational Guidelines for the World Heritage Convention. The experience that has been gained since 2000, particularly through the involvement of the public at the local level, has highlighted issues for legislative review that will pay more attention to traditional management, skills development, monitoring, and local government responsibilities, than to policing. The aim is to enable the public to protect archaeological and other heritage resources because they are significant to them and not only because there is a law that prohibits their destruction without a permit. Successful implementation will continue to depend on the political value that these resources are perceived to have in a country where historical places of the 20th century generally have more heritage interest than archaeology.
Occupational Health Challenges for Immigrant Workers
Authors: Ahonen Emily Q.
Published: October 2019

Occupational health and safety concerns classically encompass conditions and hazards in workplaces which, with sufficient exposure, can lead to injury, distress, illness, or death. The ways in which work is organized and the arrangements under which people are employed have also been linked to worker health. Migrants are people who cross borders away from their usual place of residence, and about one in seven people worldwide is a migrant. Terms like “immigrant” and “emigrant” refer to the direction of that movement relative to the stance of the speaker. Any person who might be classified as a migrant and who works or seeks to work is an immigrant worker and may face challenges to safety, health, and well-being related to the work he or she does. The economic, legal, and social circumstances of migrant workers can place them into employment and working conditions that endanger their safety, health, or well-being. While action in support of migrant worker health must be based on systematic understanding of these individuals’ needs, full understanding the possible dangers to migrant worker health is limited by conceptual and practical challenges to public health surveillance and research about migrant workers. Furthermore, intervention in support of migrant worker health must balance tensions between high-risk and population-based approaches and need to address the broader, structural circumstances that pattern the health-related experiences of migrant workers. Considering the relationships between work and health that include but go beyond workplace hazards and occupational injury, and engaging with the ways in which structural influences act on health through work, are complex endeavors. Without more critically engaging with these issues, however, there is a risk of undermining the effectiveness of efforts to improve the lot of migrant workers by “othering” the workers or by failing to focus on what is causing the occupational safety and health concern in the first place—the characteristics of the work people do. Action in support of migrant workers should therefore aim to ameliorate structural factors that place migrants into disadvantageous conditions while working to improve conditions for all workers.
The Constitution of the United States and Foreign Relations
Authors: Flaherty Martin S.
Published: October 2019

Foreign relations under the US Constitution starts with the paradox, also seen in domestic matters, of relatively scant text providing guidance for the exercise of vast power. Founding understandings, structural inference, and ongoing constitutional custom and precedent have filled in much, though hardly all, of the framework over the course of two hundred years. As a result, two basic questions frame the relationship between the Constitution and US foreign policy: (1) which parts of the US government, alone or in combination, properly exercise authority in the making of foreign policy; and (2) once made, what is the status of the nation’s international legal obligations in the US domestic legal system.

The making of American foreign policy is framed by the Constitution’s commitment to separation of powers. Congress, the president, and the courts are all allocated discrete yet significant foreign affairs authority. Determining the exact borders and overlaps in areas such as the use of military force, emergency measures, and treaty termination continues to generate controversy. The status of international law in the US legal system in the first instance turns on whether resulting obligations derive from agreements or custom. The United States enters into international agreements in three ways: treaties, congressional-executive agreements, and sole executive agreements. Complex doctrine deals with the domestic applicability of treaties in particular. US courts primarily apply customary international law in two basic ways. They can exercise a version of their common lawmaking authority to fashion rules of decision based on international custom. They also apply customary international law when incorporated into domestic law by statute.
Vinaya Rules for Monks and Nuns
Authors: Heirman Ann
Published: October 2019

Vinaya rules are stipulations and advice that guide the Buddhist community (saṃgha) of monks and nuns. They are generally considered to be the basis of monastic life. Without these rules, there is no saṃgha; and without the saṃgha, so it is said, there is no dharma (doctrine). While the rules are attributed to the Buddha, it is clear that they developed over time, influenced by the continuous spread of the Buddhist community throughout the Indian subcontinent in the centuries following the Buddha’s demise. Different traditions gradually arose, each with its own set of vinaya rules. These rules display many similarities, but also differ in some significant respects.

With the spread of the Buddhist saṃgha in South, Southeast, and East Asia in the first centuries ce, new guidelines were added to the traditional Indian vinaya rules. Although these rules have their own identifying terms—such as “bodhisattva rules” or “rules of purity”—they are often also designated by the term “vinaya,” in modern times used as a concept that encompasses all monastic, and sometimes even lay, Buddhist guidelines. In addition, many manuals and commentaries were written, adding further guiding principles. When written by very inspirational masters, these commentaries sometimes superseded the original vinaya guidelines. This phenomenon led to greater regional interpretation of how vinaya ought to be understood.
The Abolition of Brazilian Slavery, 1864–1888
Authors: Salles Ricardo
Published: October 2019

Brazil was the last Western country to abolish slavery, which it did in 1888. As a colonial institution, slavery was present in all regions and in almost all free and freed strata of the population. Emancipation only became an issue in the political sphere when it was raised by the imperial government in the second half of the decade of the 1860s, after the defeat of the Confederacy in the US Civil War and during the war against Paraguay. In 1871, new legislation, despite the initial opposition from slave owners and their political representatives, set up a process of gradual emancipation. By the end of the century, slavery would have disappeared, or would have become residual, without major disruptions to the economy or the land property regime.

By the end of the 1870s, however, popular opposition to slavery, demanding its immediate abolition without any kind of compensation to former slave owners, grew in parliament and as a mass movement. Abolitionist organizations spread across the country during the first half of the 1880s. Stimulated by the direct actions of some of these abolitionist organizations, resistance to slavery intensified and became increasingly a struggle against slavery itself and not only for individual or collective freedom. Incapable of controlling the situation, the imperial government finally passed a law in parliament granting immediate and unconditional abolition on May 13, 1888.
José de San Martín and Indigenous Relations in the South Andean Borderlands
Authors: Zarley Jesse
Published: October 2019

Napoleon Bonaparte’s 1807 invasion of Spain and Portugal set in motion a transatlantic imperial crisis that, within two decades, resulted in Spain’s losing nearly all of its American possessions. Typically, the founding of most Spanish South American nations is attributed to the heroic leadership of the great liberators: Simón Bolívar and José de San Martín. While San Martín is most famous for organizing the Army of the Andes that carried out the liberation of Chile, parts of Peru, and eventually, in 1822, reunited with Bolívar in Ecuador, his time in western Río de la Plata building his army is less understood. From 1814 until 1817, General San Martín took up residence in the western Río de la Plata (Argentina) city of Mendoza to build an army capable of defeating Spanish rule in Chile and Peru. To receive permission to cross the Andes westward into Chile, San Martín needed more than soldiers well trained in European military style and horses: he needed to negotiate with the local Pehuenche people—part of the broader Mapuche peoples of southern Chile and western Río de la Plata—who had successfully resisted Spanish conquest for centuries.

Before San Martín could cross the Andes to invade Chile, he participated in two interethnic diplomatic rituals known as parlamentos in Spanish and koyang in Mapudungun, with the Pehuenche. Nearly forty recorded Spanish–Mapuche parlamentos had taken place in Chile and near Mendoza since 1593. In the two 1816 parlamentos, interpreters translated the negotiations between Pehuenche representatives and San Martín over the exchange of horses, the giving of gifts, the recognition of Pehuenche dominion, and permission for the Army of the Andes to cross the mountains west to Chile. While San Martín chose to spread news of this agreement to confuse the Spanish forces in Chile as to the location of their crossing, opting not to cross Pehuenche lands, these parlamentos nevertheless speak to the power and importance of Pehuenche political traditions during the Age of Revolution.
Tiçiyotl and Titiçih: Late Postclassic and Early Colonial Nahua Healing, Diagnosis, and Prognosis
Authors: Polanco Edward
Published: October 2019

Nahua peoples in central Mexico in the late postclassic period (1200–1521) and the early colonial period (1521–1650) had a sophisticated and complex system of healing known as tiçiyotl. Titiçih, the practitioners of tiçiyotl, were men and women that had specialized knowledge of rocks, plants, minerals, and animals. They used these materials to treat diseases and injuries. Furthermore, titiçih used tlapohualiztli (the interpretation of objects to obtain information from nonhuman forces) to ascertain the source of a person’s ailment. For this purpose, male and female titiçih interpreted cords, water, tossed corn kernels, and they measured body parts. Titiçih could also ingest entheogenic substances (materials that released the divinity within itself) to communicate with nonhuman forces and thus diagnose and prognosticate a patient’s condition. Once a tiçitl obtained the necessary information to understand his or her patient’s affliction, he or she created and provided the necessary pahtli (a concoction used to treat an injury, illness, or condition) for the infirm person. Finally, titiçih performed important ritual offerings before, during, and after healing that insured the compliance of nonhuman forces to restore and maintain their patients’ health.
Economy in Brazil in the 20th Century
Authors: Klein Herbert S. , Vidal Luna Francisco
Published: October 2019

The 20th century represents a crucial period in Brazil’s economic history, when an agrarian, rural-dominated society became an urban, industrialized country with a complex financial sector and a large service sector. This economic transformation fueled by coffee exports led to profound demographic and social changes as millions of European and Asian immigrants were integrated into Brazilian society, followed by a massive shift of native-born migrants from the northeast to the dynamic southeast of Brazil, particularly for the state of São Paulo, which became the richest, most industrialized, and most populous state of the nation. The second half of the 20th century saw the creation of a modern industrial sector and the modernization of national agriculture, which in the 21st century made Brazil one of the most important producers of grain and animal protein in the world.
Valuation of Wetlands Preservation
Authors: Dehnhardt Alexandra , Häfner Kati , Blankenbach Anna-Marie , Meyerhoff Jürgen
Published: October 2019

All types of wetlands around the world are heavily threatened. According to the Ramsar Convention on Wetlands, they comprise “areas of marsh, fen, peatland or water, whether natural or artificial, permanent or temporary, with water that is static or flowing, fresh, brackish, or salt.” While they are estimated still to cover 1,280 million hectares worldwide, large shares of wetlands were destroyed during the 20th century, mainly as a result of land use changes. According to the Millennium Ecosystem Assessment (MEA), this applies above all to North America, Europe, Australia, and New Zealand, but wetlands were also heavily degraded in other parts of the world. Moreover, degradation is expected to accelerate in the future due to global environmental change. These developments are alarming because wetlands deliver a broad range of ecosystem services to societies, contributing significantly to human well-being. Among those services are water supply and purification, flood regulation, climate regulation, and opportunities for recreation, to name only a few. The benefits humans derive from those services, however, often are not reflected in markets as they are public goods in nature. Thus, arguing in favor of the preservation of wetlands requires, inter alia, to make the non-marketed economic benefits more visible and comparable to those from alternative—generally private—uses of converted wetlands, which are often much smaller. The significance of the non-market value of wetland services has been demonstrated in the literature: the benefits derived from wetlands have been one of the most frequently investigated topics in environmental economics and are integrated in meta-analyses devoted to synthesizing the present knowledge about the value of wetlands. The meta-analyses that cover both different types of wetlands in different landscapes as well as different geographical regions are supplemented by recent primary studies on topics of increasing importance such as floodplains and peatlands, as they bear, for example, a large flood regulation and climate change mitigation potential, respectively. The results underpin that the conversion of wetlands is accompanied by significant losses in benefits. Moreover, wetland preservation is economically beneficial given the large number of ecosystem services provided by wetland ecosystems. Thus, decision-making that might affect the status and amount of wetlands directly or indirectly should consider the full range of benefits of wetland ecosystems.
Age and the distribution of major injury across a national trauma system
Authors: Dixon Jan Robert , Lecky Fiona , Bouamra Omar , Dixon Paul , Wilson Faye , Edwards Antoinette , Eardley Will
Published: October 2019

Background

Trauma places a significant burden on healthcare services, and its management impacts greatly on the injured patient. The demographic of major trauma is changing as the population ages, increasingly unveiling gaps in processes of managing older patients. Key to improving patient care is the ability to characterise current patient distribution.

Objectives

There is no contemporary evidence available to characterise how age impacts on trauma patient distribution at a national level. Through an analysis of the Trauma Audit Research Network (TARN) database, we describe the nature of Major Trauma in England since the configuration of regional trauma networks, with focus on injury distribution, ultimate treating institution and any transfer in-between.

Methods

The TARN database was analysed for all patients presenting from April 2012 to the end of October 2017 in NHS England.

Results

About 307,307 patients were included, of which 63.8% presented directly to a non-specialist hospital (trauma unit (TU)). Fall from standing height in older patients, presenting and largely remaining in TUs, dominates the English trauma caseload. Contrary to perception, major trauma patients currently are being cared for in both specialist (major trauma centres (MTCs)) and non-specialist (TU) hospitals. Paediatric trauma accounts for <5% of trauma cases and is focussed on paediatric MTCs.

Conclusions

Within adult major trauma patients in England, mechanism of injury is dominated by low level falls, particularly in older people. These patients are predominately cared for in TUs. This work illustrates the reality of current care pathways for major trauma patients in England in the recently configured regional trauma networks.
Decoding the relationship between ageing and amyotrophic lateral sclerosis: a cellular perspective
Authors: Pandya Virenkumar A , Patani Rickie
Published: October 2019

With an ageing population comes an inevitable increase in the prevalence of age-associated neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), a relentlessly progressive and universally fatal disease characterized by the degeneration of upper and lower motor neurons within the brain and spinal cord. Indeed, the physiological process of ageing causes a variety of molecular and cellular phenotypes. With dysfunction at the neuromuscular junction implicated as a key pathological mechanism in ALS, and each lower motor unit cell type vulnerable to its own set of age-related phenotypes, the effects of ageing might in fact prove a prerequisite to ALS, rendering the cells susceptible to disease-specific mechanisms. Moreover, we discuss evidence for overlap between age and ALS-associated hallmarks, potentially implicating cell type-specific ageing as a key contributor to this multifactorial and complex disease. With a dearth of disease-modifying therapy currently available for ALS patients and a substantial failure in bench to bedside translation of other potential therapies, the unification of research in ageing and ALS requires high fidelity models to better recapitulate age-related human disease and will ultimately yield more reliable candidate therapeutics for patients, with the aim of enhancing healthspan and life expectancy.
Multi-Item Discriminability Pattern to Faces in Developmental Prosopagnosia Reveals Distinct Mechanisms of Face Processing
Authors: Tian Xue , Wang Ruosi , Zhao Yuanfang , Zhen Zonglei , Song Yiying , Liu Jia
Published: October 2019

Previous studies have shown that individuals with developmental prosopagnosia (DP) show specific deficits in face processing. However, the mechanism underlying the deficits remains largely unknown. One hypothesis suggests that DP shares the same mechanism as normal population, though their faces processing is disproportionally impaired. An alternative hypothesis emphasizes a qualitatively different mechanism of DP processing faces. To test these hypotheses, we instructed DP and normal individuals to perceive faces and objects. Instead of calculating accuracy averaging across stimulus items, we used the discrimination accuracy for each item to construct a multi-item discriminability pattern. We found DP’s discriminability pattern was less similar to that of normal individuals when perceiving faces than perceiving objects, suggesting that DP has qualitatively different mechanism in representing faces. A functional magnetic resonance imaging study was conducted to reveal the neural basis and found that multi-voxel activation patterns for faces in the right fusiform face area and occipital face area of DP were deviated away from the mean activation pattern of normal individuals. Further, the face representation was more heterogeneous in DP, suggesting that deficits of DP may come from multiple sources. In short, our study provides the first direct evidence that DP processes faces qualitatively different from normal population.
Temporal Differences in Interneuron Invasion of Neocortex and Piriform Cortex during Mouse Cortical Development
Authors: Hsing Hsiang-Wei , Zhuang Zi-Hui , Niou Zhen-Xian , Chou Shen-Ju
Published: October 2019

Establishing a balance between excitation and inhibition is critical for brain functions. However, how inhibitory interneurons (INs) generated in the ventral telencephalon integrate with the excitatory neurons generated in the dorsal telencephalon remains elusive. Previous studies showed that INs migrating tangentially to enter the neocortex (NCx), remain in the migratory stream for days before invading the cortical plate during late corticogenesis. Here we show that in developing mouse cortices, INs in the piriform cortex (PCx; the major olfactory cortex) distribute differently from those in the NCx. We provide evidence that during development INs invade and mature earlier in PCx than in NCx, likely owing to the lack of CXCR4 expression in INs from PCx compared to those in NCx. We analyzed IN distribution patterns in Lhx2 cKO mice, where projection neurons in the lateral NCx are re-fated to generate an ectopic PCx (ePCx). The PCx-specific IN distribution patterns found in ePCx suggest that properties of PCx projection neurons regulate IN distribution. Collectively, our results show that the timing of IN invasion in the developing PCx fundamentally differs from what is known in the NCx. Further, our results suggest that projection neurons instruct the PCx-specific pattern of IN distribution.
A case report: metastasis of melanoma to the heart in an era of immunotherapy
Authors: Poulsen Christian B , Weile Kathrine S , Schmidt Henrik , Poulsen Steen H
Published: October 2019

Background

Cardiac metastasis of melanoma rarely causes heart failure symptoms and the recognition of cardiac involvement is in most cases first established post-mortem. Surgical removal might be considered in selected cases in patients with an inflow or outflow tract obstruction even though the survival remains poor. Frequently, the metastasis cannot be removed and therapeutic options include conventional chemotherapy or immunotherapy, which is currently recommended as first-line treatment. Since the introduction of immunotherapy survival in metastatic disease has significantly increased but data on patients treated for melanoma with cardiac involvement are scarce.

Case summary

A 65-year-old man presented with dyspnoea and fatigue. Computed tomography scan revealed tumour processes in the heart, which was confirmed on echocardiography. Biopsies taken from fluorodeoxyglucose positron emission tomography positive lymph nodes in the axilla and groin showed melanoma. Analyses did not reveal BRAF mutation and the PD-L1 expression in tumour cells was below 1%. Treatment with ipilimumab and nivolumab was initiated and cardiopulmonary symptoms subsided during the following months with significant reduction in cardiac metastasis on echocardiography. Unfortunately, the patient developed immune checkpoint inhibitor-induced colitis and could no longer continue on the therapy. Due to development of extra-cardiac and cerebral metastasis, he was referred to palliative care.

Discussion

This case demonstrates that timely treatment with immunotherapy could be a safe and effective option for melanoma with cardiac involvement. During treatment, the patient developed severe colitis, a known side effect to immunotherapy. Though this often can be managed with steroids it complicates further treatment.
Evolutionary Analysis of Bile Acid-Conjugating Enzymes Reveals a Complex Duplication and Reciprocal Loss History
Authors: Kirilenko Bogdan M , Hagey Lee R , Barnes Stephen , Falany Charles N , Hiller Michael
Published: October 2019

To fulfill their physiological functions, bile acids are conjugated with amino acids. In humans, conjugation is catalyzed by bile acid coenzyme A: amino acid N-acyltransferase (BAAT), an enzyme with a highly conserved catalytic triad in its active site. Interestingly, the conjugated amino acids are highly variable among mammals, with some species conjugating bile acids with both glycine and taurine, whereas others conjugate only taurine. The genetic origin of these bile acid conjugation differences is unknown. Here, we tested whether mutations in BAAT’s catalytic triad could explain bile acid conjugation differences. Our comparative analysis of 118 mammals first revealed that the ancestor of placental mammals and marsupials possessed two genes, BAAT and BAATP1, that arose by a tandem duplication. This duplication was followed by numerous gene losses, including BAATP1 in humans. Losses of either BAAT or BAATP1 largely happened in a reciprocal fashion, suggesting that a single conjugating enzyme is generally sufficient for mammals. In intact BAAT and BAATP1 genes, we observed multiple changes in the catalytic triad between Cys and Ser residues. Surprisingly, although mutagenesis experiments with the human enzyme have shown that replacing Cys for Ser greatly diminishes the glycine-conjugating ability, across mammals we found that this residue provides little power in predicting the experimentally measured amino acids that are conjugated with bile acids. This suggests that the mechanism of BAAT’s enzymatic function is incompletely understood, despite relying on a classic catalytic triad. More generally, our evolutionary analysis indicates that results of mutagenesis experiments may not easily be extrapolatable to other species.
δ-Related Biomarkers Attenuate Multiple Alzheimer’s Disease Conversion Risks and Offer Targets for Intervention
Authors: Royall Donald R , Palmer Raymond F
Published: October 2019

Background

We tested certain serum proteins’ ability to mediate the effects of demographic variables on prospective 5-year conversion to clinical “Alzheimer’s disease” from non-demented states (i.e. normal control and mild cognitive impairment). The proteins were rationally selected from previously published mediators of those same variables’ (plural posessive) association with the latent variable “δ,” a novel omnibus dementia severity metric.

Methods

Each protein’s attenuation of its risk factor’s independent association with conversion was performed using logistic regression, adjusted for education, ethnicity, self-reported diabetes mellitus, and hypertension, among initially non-demented Mexican American and non-Hispanic white (N = 772) participants in the Texas Alzheimer’s Research and Care Consortium.

Results

A total of 70 (9.1%) non-demented participants at baseline converted to “Alzheimer’s disease”, with a mean follow-up of 5.4 years. Age >80 years (odds ratio = 3.1), 30-item Geriatric Depression Scale >10/30 (odds ratio = 2.3), female gender (odds ratio = 2.2), and the presence of an apolipoprotein E ε4 allele (odds ratio = 2.4) were independently associated with prospective conversion. These effects were fully attenuated by five serum proteins: age: insulin-like growth factor-binding protein 2 and epidermal growth factor receptor 1; depression: resistin; gender: thrombopoietin; and apolipoprotein E: C-reactive protein.

Conclusion

Clinical dementia arises from the sum of independent δ-related processes. This analysis provides proof of concept for the rational selection of antidementia targets and offers a foundation for precision antidementia therapy.
Group velocity maps using subspace and Trans-dimensional inversions: ambient noise tomography in the Western part of Java, Indonesia
Authors: Rosalia Shindy , Cummins Phil , Widiyantoro Sri , Yudistira Tedi , Nugraha Andri Dian , Hawkins Rhys
Published: October 2019

In this paper, we compare two different methods for group velocity inversion: iterative, least-squares subspace optimization, and probabilistic sampling based on the Trans-dimensional Bayesian method with tree-based wavelet parameterization. The wavelet parameterization used a hierarchical prior for wavelet coefficients which could adapt to the data. We applied these inversion methods for ambient noise tomography of the western part of Java, Indonesia. This area is an area prone to multiple geological hazards due to its proximity to the subduction of the Australia Plate beneath Eurasia. It is therefore important to have a better understanding of upper crustal structure to support seismic hazard and disaster mitigation efforts in this area. We utilized a new waveform dataset collected from 85 temporary seismometers deployed during 2016–2018. Cross-correlation of the waveform data was applied to retrieve empirical Rayleigh wave Green's functions between station pairs, and the spatial distribution of group velocity was obtained by inverting dispersion curves. Our results show that, although computationally expensive, the Trans-dimensional Bayesian approach offered important advantages over optimization, including more effective explorative of the model space and more robust characterization of the spatial pattern of Rayleigh wave group velocity. Meanwhile, the iterative, least-square subspace optimization suffered from the subjectivity of choice for reference velocity model and regularization parameter values. Our Rayleigh wave group velocity results show that for short (1–10 s) periods group velocity correlates well with surface geology, and for longer periods (13–25 s) it correlates with centers of volcanic activity.
From peer-based to peer-led: redefining the role of peers across the hepatitis C care pathway: HepCare Europe
Authors: Surey Julian , Menezes Dee , Francis Marie , Gibbons John , Sultan Binta , Miah Ala , Abubakar Ibrahim , Story Alistair
Published: October 2019

Background

HCV infection disproportionately affects underserved populations such as homeless individuals, people who inject drugs and prison populations. Peer advocacy can enable active engagement with healthcare services and increase the likelihood of favourable treatment outcomes.

Objectives

This observational study aims to assess the burden of disease in these underserved populations and describe the role of peer support in linking these individuals to specialist treatment services.

Methods

Services were identified if they had a high proportion of individuals with risk factors for HCV, such as injecting drug use or homelessness. Individuals were screened for HCV using point-of-care tests and a portable FibroScan. All positive cases received peer support for linkage to specialist care. Information was gathered on risk factors, demographics and follow-up information regarding linkage to care and treatment outcomes.

Results

A total of 461 individuals were screened, of which 197 (42.7%) were chronically infected with HCV. Referral was made to secondary care for 176 (89.3%) and all received peer support, with 104 (52.8%) individuals engaged with treatment centres. Of these, 89 (85.6%) started treatment and 76 (85.4%) had a favourable outcome. Factors associated with not being approved for treatment were recent homelessness, younger age and current crack cocaine injecting.

Conclusions

Highly trained peer support workers working as part of a specialist outreach clinical team help to identify a high proportion of individuals exposed to HCV, achieve high rates of engagement with treatment services and maintain high rates of treatment success amongst a population with complex needs.
Identification of Metagenomics Structure and Function Associated With Temporal Changes in Rat (Rattus norvegicus) Skin Microbiome During Health and Cutaneous Burn
Authors: Sanjar Fatemeh , Weaver Alan J , Peacock Trent J , Nguyen Jesse Q , Brandenburg Kenneth S , Leung Kai P
Published: October 2019

The cutaneous skin microbiome is host to a vast ensemble of resident microbes that provide essential capabilities including protection of skin barrier integrity and modulation of the host immune response. Cutaneous burn-injury promotes alteration of cutaneous and systemic immune response that can affect both commensal and pathogenic microbes. A cross-sectional study of a limited number of burn patients revealed a difference in the bacteriome of burned versus control participants. Temporal changes of the skin microbiome during health and cutaneous burn-injury remains largely unknown. Furthermore, how this microbial shift relates to community function in the collective metagenome remain elusive. Due to cost considerations and reduced healing time, rodents are frequently used in burn research, despite inherent physiological differences between rodents and human skin. Using a rat burn model, a longitudinal study was conducted to characterize the rat skin bacterial residents and associated community functions in states of health (n = 30) (sham-burned) and when compromised by burn-injury (n = 24). To address the knowledge gap, traumatic thermal injury and disruption of cutaneous surface is associated with genus-level changes in the microbiota, reduced bacterial richness, and altered representation of bacterial genes and associated predicted functions across different skin microbial communities. These findings demonstrate that, upon burn-injury, there is a shift in diversity of the skin’s organismal assemblages, yielding a core microbiome that is distinct at the genome and functional level. Moreover, deviations from the core community correlate with temporal changes post-injury and community transition from the state of cutaneous health to disease (burn-injury).
Mapping User-Centric Internet Geographies: How Similar are Countries in Their Web Use Patterns?
Authors: Ng Yee Man Margaret , Taneja Harsh
Published: October 2019

With half the world now online, a handful of websites dominate globally. Yet little is known about the homogeneity or geographical distinctness of global web use patterns. Focusing beyond popular sites, we inquired into how and why countries are similar in their web use patterns, developing a framework drawing on the literatures on media globalization, as well as Internet geographies. To compute similarities in web use between countries, we utilized an algorithm that considered both ranking positions and overlap counts on ranked lists of the 100 most popular websites for 174 countries, totaling 6,252 unique websites. Findings from a network analysis and from regressions suggest that countries with similar languages and shared borders, as well as those vastly different in their Internet market sizes, tend to have similar web use patterns. Neither are countries particularly similar to the US in web use nor does the prevalence of English speakers have an influence.
Clinical Validity of the PROMIS Pediatric Sleep Measures across Populations of Children with Chronic Illnesses and Neurodevelopment Disorders
Authors: Meltzer Lisa J , Forrest Christopher B , de la Motte Anna , Bevans Katherine B
Published: October 2019

Objective

To examine the clinical validity of the Patient Reported Outcome Measurement Information System (PROMIS) Pediatric Sleep Disturbance (SD) and Sleep-Related Impairment (SRI) short forms.

Methods

Youth (8–17 years) from clinical populations with known SDs (sleep clinic n = 126, autism n = 276, asthma n = 82, asthma + eczema n = 68) and the general population (n = 902) completed the PROMIS Pediatric SD and SRI 8-item short forms, along with established measures of sleep (Children’s Report of Sleep Patterns, Sleep Habits Survey), PROMIS Pediatric Fatigue, and parent-reported clinical indicators (does child have sleep problem, use melatonin, use prescription sleep medication).

Results

Confirmatory factor analyses demonstrated factorial invariance for all clinical groups. Significant differences between the general population and clinical groups were found for SD and SRI (medium to large effect sizes). Convergent validity was demonstrated through separate hierarchical regression models that showed significant associations between parent-reported clinical indicators and SD and SRI, above and beyond clinical group, as well as moderate to strong correlations between the PROMIS sleep measures and both established measures of sleep and fatigue.

Conclusions

The PROMIS Pediatric SD and SRI short forms provide clinicians and researchers a brief, accurate, and valid way to measure patient-reported sleep outcomes in pediatric populations.
Combining Multiple Imputation and Hidden Markov Modeling to Obtain Consistent Estimates of Employment Status
Authors: Boeschoten Laura , Filipponi Danila , Varriale Roberta
Published: October 2019

Recently, a method was proposed that combines multiple imputation and latent class analysis (MILC) to correct for misclassification in combined data sets. A multiply imputed data set is generated which can be used to estimate different statistics of interest in a straightforward manner and can ensure that uncertainty due to misclassification is incorporated in the estimate of the total variance. In this article, MILC is extended by using hidden Markov modeling so that it can handle longitudinal data and correspondingly create multiple imputations for multiple time points. Recently, many researchers have investigated the use of hidden Markov modeling to estimate employment status rates using a combined data set consisting of data originating from the Labor Force Survey (LFS) and register data; this combined data set is used for the setup of the simulation study performed in this article. Furthermore, the proposed method is applied to an Italian combined LFS-register data set. We demonstrate how the MILC method can be extended to create imputations of scores for multiple time points and thereby show how the method can be adapted to practical situations.
Populus euphratica WRKY1 binds the promoter of H+-ATPase gene to enhance gene expression and salt tolerance
Authors: Yao Jun , Shen Zedan , Zhang Yanli , Wu Xia , Wang Jianhui , Sa Gang , Zhang Yuhong , Zhang Huilong , Deng Chen , Liu Jian , Hou Siyuan , Zhang Ying , Zhang Yinan , Zhao Nan , Deng Shurong , Lin Shanzhi , Zhao Rui , Chen Shaoliang
Published: October 2019

Plasma membrane proton pumps play a crucial role in maintaining ionic homeostasis in salt-resistant Populus euphratica under saline conditions. High levels of NaCl (200 mM) induced PeHA1 expression in P. euphratica roots and leaves. We isolated a 2022 bp promoter fragment upstream of the translational start of PeHA1 from P. euphratica. The promoter–reporter construct PeHA1-pro::GUS was transferred to tobacco plants, demonstrating that β-glucuronidase activities increased in root, leaf, and stem tissues under salt stress. DNA affinity purification sequencing revealed that PeWRKY1 protein targeted the PeHA1 gene. We assessed the salt-induced transcriptional response of PeWRKY1 and its interaction with PeHA1 in P. euphratica. PeWRKY1 binding to the PeHA1 W-box in the promoter region was verified by a yeast one-hybrid assay, EMSA, luciferase reporter assay, and virus-induced gene silencing. Transgenic tobacco plants overexpressing PeWRKY1 had improved expression of NtHA4, which has a cis-acting W-box in the regulatory region, and improved H+ pumping activity in both in vivo and in vitro assays. We conclude that salt stress up-regulated PeHA1 transcription due to the binding of PeWRKY1 to the W-box in the promoter region of PeHA1. Thus, we conclude that enhanced H+ pumping activity enabled salt-stressed plants to retain Na+ homeostasis.
The MOSDEF survey: direct-method metallicities and ISM conditions at z ∼ 1.5–3.5
Authors: Sanders Ryan L , Shapley Alice E , Reddy Naveen A , Kriek Mariska , Siana Brian , Coil Alison L , Mobasher Bahram , Shivaei Irene , Freeman William R , Azadi Mojegan , Price Sedona H , Leung Gene , Fetherolf Tara , de Groot Laura , Zick Tom , Fornasini Francesca M , Barro Guillermo
Published: October 2019

We present detections of [O iii] λ4363 and direct-method metallicities for star-forming galaxies at z = 1.7–3.6. We combine new measurements from the MOSFIRE Deep Evolution Field (MOSDEF) survey with literature sources to construct a sample of 18 galaxies with direct-method metallicities at z > 1, spanning 7.5 < 12+log(O/H) < 8.2 and log(M*/M⊙) = 7–10. We find that strong-line calibrations based on local analogues of high-redshift galaxies reliably reproduce the metallicity of the z > 1 sample on average. We construct the first mass–metallicity relation at z > 1 based purely on direct-method O/H, finding a slope that is consistent with strong-line results. Direct-method O/H evolves by ≲0.1 dex at fixed M* and star formation rate from z ∼ 0 to 2.2. We employ photoionization models to constrain the ionization parameter and ionizing spectrum in the high-redshift sample. Stellar models with supersolar O/Fe and binary evolution of massive stars are required to reproduce the observed strong-line ratios. We find that the z > 1 sample falls on the z ∼ 0 relation between ionization parameter and O/H, suggesting no evolution of this relation from z ∼ 0 to z ∼ 2. These results suggest that the offset of the strong-line ratios of this sample from local excitation sequences is driven primarily by a harder ionizing spectrum at fixed nebular metallicity compared to what is typical at z ∼ 0, naturally explained by supersolar O/Fe at high redshift caused by rapid formation time-scales. Given the extreme nature of our z > 1 sample, the implications for representative z ∼ 2 galaxy samples at ∼1010 M⊙ are unclear, but similarities to z > 6 galaxies suggest that these conclusions can be extended to galaxies in the epoch of reionization.