bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Clofazimine Dosing on Treatment Shortening of the First-Line Regimen in a Mouse Model of Tuberculosis
Authors: Ammerman Nicole C. , Swanson Rosemary V. , Bautista Elaine M. , Almeida Deepak V. , Saini Vikram , Omansen Till F. , Guo Haidan , Chang Yong Seok , Li Si-Yang , Tapley Asa , Tasneen Rokeya , Tyagi Sandeep , Betoudji Fabrice , Moodley Chivonne , Ngcobo Bongani , Pillay Logan , Bester Linda A. , Singh Sanil D. , Chaisson Richard E. , Nuermberger Eric , Grosset Jacques H. 
Published: May 2018

ABSTRACT
The antileprosy drug clofazimine was recently repurposed as part of a newly endorsed short-course regimen for multidrug-resistant tuberculosis. It also enables significant treatment shortening when added to the first-line regimen for drug-susceptible tuberculosis in a mouse model. However, clofazimine causes dose- and duration-dependent skin discoloration in patients, and the optimal clofazimine dosing strategy in the context of the first-line regimen is unknown. We utilized a well-established mouse model to systematically address the impacts of duration, dose, and companion drugs on the treatment-shortening activity of clofazimine in the first-line regimen. In all studies, the primary outcome was relapse-free cure (culture-negative lungs) 6 months after stopping treatment, and the secondary outcome was bactericidal activity, i.e., the decline in the lung bacterial burden during treatment. Our findings indicate that clofazimine activity is most potent when coadministered with first-line drugs continuously throughout treatment and that equivalent treatment-shortening results are obtained with half the dose commonly used in mice. However, our studies also suggest that clofazimine at low exposures may have negative impacts on treatment outcomes, an effect that was evident only after the first 3 months of treatment. These data provide a sound evidence base to inform clofazimine dosing strategies to optimize the antituberculosis effect while minimizing skin discoloration. The results also underscore the importance of conducting long-term studies to allow the full evaluation of drugs administered in combination over long durations.
Hepcidin Protects against Lethal Escherichia coli Sepsis in Mice Inoculated with Isolates from Septic Patients
Authors: Stefanova Deborah , Raychev Antoan , Deville Jaime , Humphries Romney , Campeau Shelley , Ruchala Piotr , Nemeth Elizabeta , Ganz Tomas , Bulut Yonca 
Published: May 2018

ABSTRACT

Iron is an essential micronutrient for most microbes and their hosts. Mammalian hosts respond to infection by inducing the iron-regulatory hormone hepcidin, which causes iron sequestration and a rapid decrease in the plasma and extracellular iron concentration (hypoferremia). Previous studies showed that hepcidin regulation of iron is essential for protection from infection-associated mortality with the siderophilic pathogens
Yersinia enterocolitica
and
Vibrio vulnificus
. However, the evolutionary conservation of the hypoferremic response to infection suggests that not only rare siderophilic bacteria but also common pathogens may be targeted by this mechanism. We tested 10 clinical isolates of
Escherichia coli
from children with sepsis and found that both genetic iron overload (by hepcidin-1 knockout [HKO]) and iatrogenic iron overload (by intravenous iron) potentiated infection with 8 out of the 10 studied isolates: after peritoneal injection of
E. coli
, iron-loaded mice developed sepsis with 60% to 100% mortality within 24 h, while control wild-type mice suffered 0% mortality. Using one strain for more detailed study, we show that iron overload allows rapid bacterial multiplication and dissemination. We further found that the presence of non-transferrin-bound iron (NTBI) in the circulation is more important than total plasma or tissue iron in rendering mice susceptible to infection and mortality. Postinfection treatment of HKO mice with just two doses of the hepcidin agonist PR73 abolished NTBI and completely prevented sepsis-associated mortality. We demonstrate that the siderophilic phenotype extends to clinically common pathogens. The use of hepcidin agonists promises to be an effective early intervention in patients with infections and dysregulated iron metabolism.
The Complement System Contributes to Functional Antibody-Mediated Responses Induced by Immunization with Plasmodium falciparum Malaria Sporozoites
Authors: Behet Marije C. , Kurtovic Liriye , van Gemert Geert-Jan , Haukes Celine M. , Siebelink-Stoter Rianne , Graumans Wouter , van de Vegte-Bolmer Marga G. , Scholzen Anja , Langereis Jeroen D. , Diavatopoulos Dimitri A. , Beeson James G. , Sauerwein Robert W. 
Published: May 2018

ABSTRACT

Long-lasting and sterile homologous protection against malaria can be achieved by the exposure of malaria-naive volunteers under chemoprophylaxis to
Plasmodium falciparum
-infected mosquitoes (chemoprophylaxis and sporozoite [CPS] immunization). While CPS-induced antibodies neutralize sporozoite infectivity
in vitro
and
in vivo
, antibody-mediated effector mechanisms are still poorly understood. Here, we investigated whether complement contributes to CPS-induced preerythrocytic immunity. Sera collected before and after CPS immunization in the presence of active or inactive complement were assessed for the recognition of homologous NF54 and heterologous NF135.C10 sporozoites, complement fixation, sporozoite lysis, and possible subsequent effects on
in vitro
sporozoite infectivity in human hepatocytes. CPS immunization induced sporozoite-specific IgM (
P
< 0.0001) and IgG (
P
= 0.001) antibodies with complement-fixing capacities (
P
< 0.0001). Sporozoite lysis (
P
= 0.017), traversal (
P
< 0.0001), and hepatocyte invasion inhibition (
P
< 0.0001) by CPS-induced antibodies were strongly enhanced in the presence of active complement. Complement-mediated invasion inhibition in the presence of CPS-induced antibodies negatively correlated with cumulative parasitemia during CPS immunizations (
P
= 0.013). While IgG antibodies similarly recognized homologous and heterologous sporozoites, IgM binding to heterologous sporozoites was reduced (
P
= 0.023). Although CPS-induced antibodies did not differ in their abilities to fix complement, lyse sporozoites, or inhibit the traversal of homologous and heterologous sporozoites, heterologous sporozoite invasion was more strongly inhibited in the presence of active complement (
P
= 0.008). These findings demonstrate that CPS-induced antibodies have complement-fixing activity, thereby significantly further enhancing the functional inhibition of homologous and heterologous sporozoite infectivity
in vitro
. The combined data highlight the importance of complement as an additional immune effector mechanism in preerythrocytic immunity after whole-parasite immunization against
Plasmodium falciparum
malaria.
What is the normal haemodynamic response to passive leg raise? A study of healthy volunteers
Authors: Elwan Mohammed H , Roshdy Ashraf , Reynolds Joseph A , Elsharkawy Eman M , Eltahan Salah M , Coats Timothy J 
Published: May 2018

ObjectivePassive leg raise (PLR) is used as self-fluid challenge to optimise fluid therapy by predicting preload responsiveness. However, there remains uncertainty around the normal haemodynamic response to PLR with resulting difficulties in application and interpretation in emergency care. We aim to define the haemodynamic responses to PLR in spontaneously breathing volunteers using a non-invasive cardiac output monitor, thoracic electrical bioimpedance, TEB (PLR-TEB).MethodsWe recruited healthy volunteers aged 18 or above. Subjects were monitored using TEB in a semirecumbent position, followed by PLR for 3 min. The procedure was repeated after 6 min at the starting position. Correlation between the two PLRs was assessed using Spearman’s r (rs). Agreement between the two PLRs was evaluated using Cohen Kappa with responsiveness defined as ≥10% increase in stroke volume. Parametric and non-parametric tests were used as appropriate to evaluate statistical significance of baseline variables between responders and non-responders.ResultsWe enrolled 50 volunteers, all haemodynamically stable at baseline, of whom 49 completed the study procedure. About half of our subjects were preload responsive. The ∆SV in the two PLRs was correlated (rs=0.68, 95% CI 0.49 to 0.8) with 85% positive concordance. Good agreement was observed with Cohen Kappa of 0.67 (95% CI 0.45 to 0.88). Responders were older and had significantly lower baseline stroke volume and cardiac output.ConclusionOur results suggest that the PLR-TEB is a feasible method in spontaneously breathing volunteers with reasonable reproducibility. The age and baseline stroke volume effect suggests a more complex underlying physiology than commonly appreciated. The fact that half of the volunteers had a positive preload response, against the 10% threshold, leads to questions about how this measurement should be used in emergency care and will help shape future patient studies.
Effect of harvest date and frequency on aspen ricegrass (Oryzopsis asperifolia) and cream-coloured vetchling (Lathyrus ochroleucus) in the boreal transition ecoregion of Saskatchewan
Authors: Foster Allan , Biligetu Bill 
Published: May 2018

Aspen forest communities of Saskatchewan, Canada, support a significant cattle population. The objectives of this study were to determine seasonal forage dry matter (DM) accumulation and evaluate repeated annual defoliation on DM yield (DMY) of aspen ricegrass (Oryzopsis asperifolia) and cream-coloured vetchling (Lathyrus ochroleucus) in the boreal transition ecoregion of east–central Saskatchewan. The experimental design was a randomized completed block with five replicates. Seasonal DMY of aspen ricegrass (p < 0.0001) was lowest in June, intermediate in July, and highest in August to October, with DMY ranging from 2.9–15.3 g m−2. Cream-coloured vetchling (p < 0.0001) had the highest DMY in July and August (5.5, 4.8 g m−2) than other months (1.2–2.3 g m−2). Single repeated defoliation, regardless of clipping date, reduced (P = 0.0098) the overall production of aspen ricegrass (Oryzopsis asperifolia) and cream-coloured vetchling (Lathyrus ochroleucus) in this study.
Petroleum geology of the Black Sea: introduction
Authors: Simmons M. D. , Tari G. C. , Okay A. I. 
Published: May 2018

Abstract
The exploration for petroleum in the Black Sea is still in its infancy. Notwithstanding the technical challenges in drilling in its deep-water regions, several geological risks require better understanding. These challenges include reservoir presence and quality (partly related to sediment provenance), and the timing and migration of hydrocarbons from source rocks relative to trap formation. In turn, these risks can only be better understood by an appreciation of the geological history of the Black Sea basins and the surrounding orogens. This history is not without ongoing controversy. The timing of basin formation, uplift of the margins and facies distribution remain issues for robust debate. This Special Publication presents the results of 15 studies that relate to the tectonostratigraphy and petroleum geology of the Black Sea. The methodologies of these studies encompass crustal structure, geodynamic evolution, stratigraphy and its regional correlation, petroleum systems, source to sink, hydrocarbon habitat and play concepts, and reviews of past exploration. They provide insight into the many ongoing controversies regarding the geological history of the Black Sea region and provide a better understanding of the geological risks that must be considered for future hydrocarbon exploration. The Black Sea remains one of the largest underexplored rift basins in the world. Although significant biogenic gas discoveries have been made within the last decade, thermogenic petroleum systems must be proven through the systematic exploration of a wide variety of play concepts.
Dose response of somatosensory cortex repeated anodal transcranial direct current stimulation on vibrotactile detection: a randomized sham-controlled trial
Authors: Folmli Brookes , Turman Bulent , Johnson Peter , Abbott Allan 
Published: May 2018

This randomized sham-controlled trial investigated anodal transcranial direct current stimulation (tDCS) over the somatosensory cortex contralateral to hand dominance for dose-response (1 mA, 20 min × 5 days) effects on vibrotactile detection thresholds (VDT). VDT was measured before and after tDCS on days 1, 3, and 5 for low- (30 Hz) and high-frequency (200 Hz) vibrations on the dominant and nondominant hands in 29 healthy adults (mean age = 22.86 yr; 15 men, 14 women). Only the dominant-hand 200-Hz VDT displayed statistically significant medium effect size improvement for mixed-model analysis of variance time-by-group interaction for active tDCS compared with sham. Post hoc contrasts were statistically significant for dominant-hand 200-Hz VDT on day 5 after tDCS compared with day 1 before tDCS, day 1 after tDCS, and day 3 before tDCS. There was a linear dose-response improvement with dominant-hand 200-Hz VDT mean difference decreasing from day 1 before tDCS peaking at −15.5% (SD = 34.9%) on day 5 after tDCS. Both groups showed learning effect trends over time for all VDT test conditions, but only the nondominant-hand 30-Hz VDT was statistically significant ( P = 0.03), although post hoc contrasts were nonsignificant after Šidák adjustment. No adverse effects for tDCS were reported. In conclusion, anodal tDCS at 1 mA, 20 min × 5 days on the dominant sensory cortex can modulate a linear improvement of dominant-hand high-frequency VDT but not low-frequency or nondominant-hand VDT. NEW & NOTEWORTHY Repeated weak anodal transcranial direct current stimulation (1 mA, 20 min) on the dominant sensory cortex provides linear improvement in dominant-hand high-frequency vibration detection thresholds. No effects were observed for low-frequency or nondominant-hand vibration detection thresholds.
U.S.-China Rivalry in Southeast Asia: Power Shift or Competitive
Coexistence?
Authors: Shambaugh David 
Published: May 2018

Abstract
U.S.-China comprehensive competition is currently playing out on an increasingly global scale. The competition's primary locus is the vast Indo-Asia-Pacific region, and it is centered in Southeast Asia. The United States and China each possess comparative advantages in the region. Beijing's advantages are predominantly economic and diplomatic, whereas Washington's are more multifaceted. Although the Barack Obama administration's “pivot” significantly raised the U.S profile in Southeast Asia, China has also expanded its presence and influence. The two powers are increasingly locked in a classic strategic competition, but the pervasive media narrative in the region holds that China is gaining the upper hand. While this gravitation toward Beijing has become a popular meme, it is not empirically accurate—as the United States still possesses substantial overall advantages. Still, the regional balance is dynamic, and the United States needs to remain comprehensively engaged—or else the balance of influence will default to China. At present, the Sino-American competition in Southeast Asia is not (yet) acute and zero-sum. Therefore, the two powers should be able to manage their tensions, limit their rivalry, and practice competitive coexistence.
The Effects of Disease on the London Missionary Society’s South Seas Missions between 1797 and 1860
Authors: Alden Jonny 
Published: May 2018

Abstract
European missionary activity enabled not only the communication of the Christian message, but facilitated the dissemination of a mélange of diseases amongst epidemiologically disparate cultural groupings. This paper explores the influence of disease upon the London Missionary Society’s South Seas missions between 1797 and 1860. I argue that disease shaped missionary activity in three central ways: Firstly, through shaping missionaries’ primary experiences; secondly, through moulding the ways in which native peoples conceptualised and responded to the Christian message; and finally, through contributing profoundly towards missionary conceptions of European superiority and the Polynesian ‘other’.
Drudges, Shrews, and Unfit Mothers
Authors: Barker John 
Published: May 2018

Abstract
Among the first Europeans to encounter and settle on the southeastern coast of New Guinea, members of the London Missionary Society contributed a large corpus of publications concerning indigenous peoples from the mid-1870s until the rise of professional anthropology in the 1920s. While these works focus mainly on the activities and concerns of men, women provide a key index of “civilization” relative to the working British middle class from which most missionaries came. This essay provides a survey of the portrayal of women in this literature over three partly overlapping periods, demonstrating a shift from racialist to moral discourses on the status of Papuan women – a shift that reflects transitions in both missionary and anthropological assumptions during this period.
Continental Philosophy and Theology
Authors: Dickinson Colby 
Published: May 2018

AbstractContinental philosophy underwent a ‘return to religion’ or a ‘theological turn’ in the late 20th Century. And yet any conversation between continental philosophy and theology must begin by addressing the perceived distance between them: that one is concerned with destroying all normative, metaphysical order (continental philosophy’s task) and the other with preserving religious identity and community in the face of an increasingly secular society (theology’s task). Colby Dickinson argues inContinental Philosophy and Theologyrather that perhaps such a tension is constitutive of the nature of order, thinking and representation which typically take dualistic forms and which might be rethought, though not necessarily abolished. Such a shift in perspective even allows one to contemplate this distance as not opting for one side over the other or by striking a middle ground, but as calling for a nondualistic theology that measures the complexity and inherently comparative nature of theological inquiry in order to realign theology’s relationship to continental philosophy entirely.
‘Solidarity not alms’: Civil rights movements contesting the evictions and denial of social rights from vulnerable European Union citizens in Sweden
Authors: Morell Ildikó Asztalos 
Published: May 2018

The chief aims of the Swedish municipality-based Facebook network SEM, ‘Solidarity with EU migrants’ [Solidaritet med EU migranter!] are to fight for better conditions and humane treatment of migrants primarily from Romania, who came to Sweden in hope of finding work and the ability to provide for their families. The site is to transmit relevant news, actions, organise money collections, political actions and alike. Those volunteers active in the group believe that ‘righteousness and solidarity’ should apply, even those who are in the grip of European Union bureaucracy. 1 Using theories of civil movements in the IT age, I elaborate on how the activists on the site respond to the challenges of the criminalisation of vulnerable European Union citizens, by balancing their engagement between the dimensions of ‘pragmatic voluntarism’ versus ‘subversive humanitarianism’. Furthermore, I explore how the site counteracts hegemonic master narratives on Roma as both idle and victims, who need to be saved from begging, by providing alternative narratives of subjectivities and identities to the Roma men and women they work with and for, seeing them as agents struggling to improve the lives of their families.
Midterm Outcomes and Return to Sports Among Athletes Undergoing Hip Arthroscopy
Authors: Perets Itay , Craig Matthew J. , Mu Brian H. , Maldonado David R. , Litrenta Jody M. , Domb Benjamin G. 
Published: May 2018

Background: Hip arthroscopy is an established surgical treatment for pathologic hip conditions in athletes. There is a paucity in the literature regarding outcomes and return to sport for athletes in the midterm. Purpose: To report minimum 5-year outcomes, return to sport, and level of sport among athletic patients who underwent hip arthroscopy. In addition, we compared 2- and 5-year outcomes to evaluate whether there is a deterioration in functional status. Study Design: Case series; Level of evidence, 4. Methods: Data were prospectively collected on all patients who underwent hip arthroscopy between February 2009 and November 2011 at 1 institution. Athletes at the high school, collegiate, or professional level who underwent hip arthroscopy and had preoperative patient-reported outcome (PRO) scores were considered for inclusion. Exclusion criteria were preoperative Tönnis grade >1 or prior ipsilateral hip conditions or surgery. Data on sports participation, competition level, and ability were collected. At a minimum of 5 years postoperatively, PROs, visual analog scale (VAS), iHOT-12 (short version of International Hip Outcome Tool), satisfaction, and postoperative complication data were collected. Results: Seventy-seven hips met all criteria, among which 66 (85.7%) had a minimum 5-year follow-up and were included. There were 37 high school, 20 collegiate, and 9 professional athletes. Mean ± SD improvements at a minimum of 5 years were as follows: modified Harris Hip Score, 66.8 ± 16.3 to 87.0 ± 14.8 ( P < .001); nonarthritic hip score, 66.2 ± 19.9 to 87.2 ± 15.2 ( P < .001); Hip Outcome Score–Sports Specific Subscale, 47.0 ± 22.4 to 79.1 ± 23.0 ( P < .001); and VAS, 5.4 ± 2.5 to 1.8 ± 2.1 ( P < .001). At latest follow-up, mean iHOT-12 was 78.8 ± 22.7, and satisfaction was 8.2. A total of 50 athletes (53 hips, 80.3%) reported that they returned to sports; 71.2% reported “same” or “higher” sport ability as compared with a year before surgery. Postoperative complications included 3 cases (4.5%) of numbness and 1 case (1.5%) of pulmonary embolism. Ten hips (15.2%) required secondary arthroscopies, and no hips were converted to total hip arthroplasty. There were no significant differences between 2- and 5-year PROs, VAS, or satisfaction. Conclusion: Midterm results of hip arthroscopy in athletes are shown to be safe and favorable. Most athletes return to sports and continue to play after 5 years with the same or higher ability.
Relationship Between Expectation of Death and Location of Death Varies by Race/Ethnicity
Authors: Romo Rafael D. , Cenzer Irena S. , Williams Brie A. , Smith Alexander K. 
Published: May 2018

Background: Older black and Latino Americans are more likely than white Americans to die in the hospital. Whether ethnic differences in expectation of death account for this disparity is unknown. Objectives: To determine whether surviving family members’ expectation of death has a differential association with site of death according to race or ethnicity. Methods: We conducted an analysis of decedents from the Health and Retirement Study, a nationally representative study of US older adults. Telephone surveys were conducted with family members for 5979 decedents (decedents were 55% were women, 85% white, 9% black, and 6% Latino). The outcome of interest was death in the hospital; the predictor variable was race/ethnicity, and the intervening variable was expectation of death. Covariates included sociodemographics (gender, age, household net worth, educational attainment level, religion) and health factors (chronic conditions, symptoms, health-care utilization). Results: Decedents’ race/ethnicity was statistically related to the expectation of death and death in the hospital. When death was not expected, whites and Latinos were more likely to die in the hospital than when death was expected (49% vs 29% for whites and 55% vs 37% for Latinos; P < .001). There was no difference in site of death according to family’s expectation of death among blacks. Conclusion: Expectation of death did not fully account for site of death and played a greater role among whites and Latinos than among black Americans. Discussing prognosis by itself is unlikely to address ethnic disparities. Other factors appear to play an important role as well.