bluuebunny/crossref_metadata_2025 huggingface dataset:
Crohn’s and Parkinson’s Disease-Associated LRRK2 Mutations Alter Type II Interferon Responses in Human CD14+ Blood Monocytes Ex Vivo
Authors: Ikezu Tsuneya , Koro Lacin , Wolozin Benjamin , Farraye Francis A. , Strongosky Audrey J. , Wszolek Zbigniew K.
Published: March 2020

The Leucine Rich Repeat Kinase 2 (LRRK2) is one of causative genes of familial Parkinson’s disease (PD). The M2397T polymorphism inLRRK2is genetically associated with sporadic Crohn’s disease (CD). LRRK2 is expressed in human CD14+monocytes, induced by interferon-γ (IFN-γ) and suppresses inflammatory activation. We hypothesize that IFN-γ-induced LRRK2 and inflammatory gene expression is altered byLRRK2genetic polymorphism found in CD and PD cases. A total of 46 CD and 51 control cases, and 16 PD cases and 16 PD-linkedLRRK2mutation cases were recruited. Live human CD14+monocytes were isolated from donors for ex vivo IFN-γ stimulation and gene expression analysis. IFN-γ potently enhancedTNFA, IL12, HLADRA1 and LRRK2expression, which was suppressed by FK506, a calcineurin-specific inhibitor, but further enhanced by LRRK2-specific kinase inhibitor (GSK2578215A). The 2397-M/M CD risk allele enhanced IFN-γ responses of CD14+cells in CD but not in control group. CD14+monocytes from G2019S and R1441CLRRK2mutated PD cases and carriers show no changes in IFN-γ responses forTNFAorIL12, reduced response forHLADRA1,and enhanced responses forLRRK2in FK506-sensitive manner. These data demonstrate that CD-associatedLRRK2mutations are significant modifiers of innate immune response in CD14+monocytes, and PD-associatedLRRK2mutation may contribute to reduced antigen presentation response.
Stabilization of the ζ-Cu10Sn3 Phase by Ni at Soldering-Relevant Temperatures
Authors: Wieser C. , Hügel W. , Martin S. , Freudenberger J. , Leineweber A.
Published: March 2020

A current issue in electrical engineering is the enhancement of the quality of solder joints. This is mainly associated with the ongoing electrification of transportation as well as the miniaturization of (power) electronics. For the reliability of solder joints, intermetallic phases in the microstructure of the solder are of great importance. The formation of the intermetallic phases in the Cu-Sn solder system was investigated for different annealing temperatures between 472 K and 623 K using pure Cu as well as Cu-1at.%Ni and Cu-3at.%Ni substrate materials. These are relevant for lead frame materials in electronic components. The Cu and Cu-Ni alloys were in contact to galvanic plated Sn. This work is focused on the unexpected formation of the hexagonal ζ-(Cu,Ni)10Sn3phase at annealing temperatures of 523–623 K, which is far below the eutectoid decomposition temperature of binary ζ-Cu10Sn3of about 855 K. By using scanning electron microscopy, energy dispersive X-ray spectroscopy, electron backscatter diffraction and X-ray diffraction the presence of the ζ phase was confirmed and its structural properties were analyzed.
Anglican Cathedrals in a Secular Society: David Martin and the Sociology of English Religion
Authors: Percy Martyn
Published: March 2020

One of the puzzles in our secular age is the resurgence in attendance at English Cathedrals. Whilst it is commonplace for sociologists and media - and sometimes church leaders - to draw attention to burgeoning membership in evangelical and charismatic churches, the Cathedrals of the Church of England represent a different kind of growth. A considerable number of attendees come to cathedral worship and significant commemorative events (e.g., Christmas, Remembrance) because the very particular ecclesial ecology of a cathedral does not normally require membership, intense fellowship or frequency in attendance. Cathedrals, therefore, are now more prominent exponents of 'low-threshold-high-reward' patterns of worship, and point to a form of ecclesial polity that was once much more common in English Anglicanism. Namely, the church serving its community as a support-based institution rather than as a member-based organisation. The sensibility of cathedral worship may now chime more deeply with those latent patterns of spirituality that remain textured and strong within the weave contemporary culture, embodying spiritual-spatial inclusion. To understand the resilience of cathedrals, and their relative growth in attendees, requires developed ecologies of English church-going that comprehend the value of the church continuing to hold its vocation as the social skin of a city, region and the nation, and a patterning of polity that continually renews the values underpinning civic society.
Lesion Size- and Location-Dependent Recruitment of Contralesional Thalamus and Motor Cortex Facilitates Recovery after Stroke in Mice
Authors: Aswendt Markus , Pallast Niklas , Wieters Frederique , Baues Mayan , Hoehn Mathias , Fink Gereon R
Published: March 2020

Brain lesions caused by cerebral ischemia or hemorrhage lead to a local breakdown of energy homeostasis followed by irreversible cell death and long-term impairment. Importantly, local brain lesions also generate remote functional and structural disturbances, which contribute to the behavioral deficit but also impact the recovery of function. While spontaneous recovery has been associated with endogenous repair mechanisms at the vascular, neural, and immune cell levels, the impact of structural plasticity on sensory-motor dysfunction and recovery thereof remains to be elucidated by longitudinal imaging in a mouse model. Here, we applied behavioral assessments, in vivo fiber tracking, and histological validation in a photothrombotic stroke mouse model. Atlas-based whole-brain structural connectivity analysis and ex vivo histology revealed secondary neurodegeneration in the ipsilesional brain areas, mostly in the dorsal sensorimotor area of the thalamus. Furthermore, we describe for the first time a lesion size-dependent increase in structural connectivity between the contralesional primary motor cortex and thalamus with the ipsilesional cortex. The involvement of the contralesional hemisphere was associated with improved functional recovery relative to lesion size. This study highlights the importance of in vivo fiber tracking and the role of the contralesional hemisphere during spontaneous functional improvement as a potential novel stroke biomarker and therapeutic targets.
Challenges in nanomedicine clinical translation
Authors: Metselaar Josbert M. , Lammers Twan
Published: March 2020

New nanomedicine formulations and novel applications of nanomedicinal drugs are reported on an almost daily basis. While academic progress and societal promise continue to shoot for the stars, industrial acceptance and clinical translation are being looked at increasingly critically. We here discuss five key challenges that need to be considered when aiming to promote the clinical translation of nanomedicines. We take the perspective of the end-stage users and consequently address the developmental path in a top-down manner. We start off by addressing central and more general issues related to practical and clinical feasibility, followed by more specific preclinical, clinical, and pharmaceutical aspects that nanomedicinal product development entails. We believe that being more aware of the end user’s perspective already early on in the nanomedicine development path will help to better oversee the efforts and investments needed, and to take optimally informed decisions with regard to market opportunities, target disease indication, clinical trial design, therapeutic endpoints, preclinical models, and formulation specifications. Critical reflections on and careful route planning in nanomedicine translation will help to promote the success of nanomedicinal drugs.
Characterization of proliferation, differentiation potential, and gene expression among clonal cultures of human dental pulp cells
Authors: Kobayashi Tomoko , Torii Daisuke , Iwata Takanori , Izumi Yuichi , Nasu Masanori , Tsutsui Takeo W.
Published: March 2020

Mesenchymal stem cells are a highly promising source of cells for regeneration therapy because of their multilineage differentiation potential. However, distinct markers for mesenchymal stem cells are not well-established. To identify new candidate marker genes for multipotent human dental pulp stem cells, we analyzed the characteristics and gene expression profiles of cell clones obtained from a single dental pulp specimen derived from an 11-year-old female patient. Fifty colony-forming single cell-derived clones were separately cultured until the cessation of growth. These clones varied in their proliferation abilities and surface marker (STRO-1 and CD146) expression patterns, as well as their odontogenic, adipogenic, and chondrogenic differentiation potentials. Four clones maintained their original differentiation potentials during long-term culture. Gene expression profile by DNA microarray analysis of five representative clones identified 1227 genes that were related to multipotency. Ninety of these 1227 genes overlapped with genes reportedly involved in ‘stemness or differentiation’. Based on the predicted locations of expressed protein products and large changes in expression levels, 14 of the 90 genes were selected as candidate dental pulp stem cell markers, particularly in relation to their multipotency characteristics. This characterization of cell clones obtained from a single specimen of human dental pulp provided information regarding new candidate marker genes for multipotent dental pulp stem cells, which could facilitate efficient analysis or enrichment of multipotent stem cells.
Impact of the quality of food sources on the wing beating of honey bee dancers
Authors: Łopuch Sylwia , Tofilski Adam
Published: March 2020

The waggle dances of honey bees provide information about the location of food sources and their quality. This study aimed to investigate how the quality of food sources affects different components of the dance. For the first time, we analysed in detail both the waggle phase and the return phase of the dance using a high-speed camera. The frequency of wing beats in the waggle phase and the frequency of wing-beating pulses in the return phase were significantly higher in foragers collecting more concentrated honey compared with foragers collecting less-concentrated honey, whereas the duration of the return phase was significantly shorter. Discriminant function analysis allowed correct classification of 88.1% of dances as referring to 60 or 40% honey concentration. In conclusion, information about the quality of food sources can be contained both in the waggle phase and in the return phase; however, the return phase appears to transfer more information about the quality of food sources.
Using a Mixed Methods Approach to Examine the Effectiveness of Inpatient Rehabilitation Services Following a Programme of Planned Bed Closures
Authors: Mutale Gabriella J. , de Motte Claire , Bailey Di
Published: March 2020

This study examined inpatient rehabilitations service in one area in England following a programme of planned bed closures in parts of the service. The study examined changes to admission rates and length of stay in the parts of the service that existed prior to and after the bed closure programme. A mixed method evaluation design was used. Quantitative data relating to admissions and length of inpatients stays bed days was compared for the 3 years up to the bed closures and for the 3 years afterwards. Similarly use of mental health sections for service users being admitted, and contacts with community mental health teams were also compared for the same 3-year pre and post period. Qualitative data from service users, carers of service users, and staff were analyzed thematically to provide an insight into any changes in rehabilitation service usage as a result of the closure programme. In the rehabilitation services that existed before and after bed closures in other parts of the service quantitative findings showed a significant reduction post-rehabilitation stay in all measures except contact with community teams. Qualitative analysis revealed that this is because rehabilitation enables a successful transition into the community and allows for effective relationships to be built between staff and service user. The reduction seen in service utilization suggests rehabilitation has the potential to reduce the revolving door to inpatient metal health care.
Haploidentical bone marrow transplant with posttransplant cyclophosphamide for sickle cell disease
Authors: Patel Dilan A. , Akinsete Adeseye M. , Fuente Josu de la , Kassim Adetola A.
Published: March 2020

Hematopoietic cell transplant (HCT) can cure both children and adults with sickle cell disease. Outcomes have historically been poor for the vast majority of patients who lack a matched sibling donor. However, the development of haploidentical HCT (haplo-HCT) with high doses of posttransplant cyclophosphamide (PTCy) has allowed for curative long-term potential with favorable transplant-related outcomes, though this has not obviated the potential for graft rejection from human leukocyte antigen mismatch and repeated red blood cell transfusions. Accordingly, multiple strategies have been developed to improve outcomes, the majority of which are based on the Johns Hopkins platform from 2012. Presently, we aim to discuss results from pertinent studies and compare outcomes with the two most recent approaches involving either thiotepa plus 200-cGy total body irradiation or 400-cGy total body irradiation. Direct comparisons are required to determine the optimized curative potential. Transplant-eligible patients must be referred to tertiary medical centers for consideration of haplo-HCT.
Comparing Provider-Led Sexual Health Counseling of Male and Female Patients Undergoing Radical Cystectomy
Authors: Gupta Natasha , Kucirka Lauren M. , Semerjian Alice , Wainger Julia , Pierorazio Phillip M. , Herati Amin S. , Bivalacqua Trinity J.
Published: March 2020

Background

Sexual dysfunction is a common quality-of-life issue among patients undergoing radical cystectomy (RC) for bladder cancer, but patients report deficiencies in sexual health counseling.

Aim

We sought to characterize provider-led sexual health counseling of patients undergoing RC and whether provider practice differs by patient gender.

Methods

We conducted a cross-sectional survey of members of the Society of Urologic Oncology to assess topics included in provider-led sexual health counseling and barriers to counseling.

Outcomes

Nonroutine counseling regarding each sexual health topic was compared for female vs male patients using chi-squared tests. Modified Poisson regression was used to examine associations between provider characteristics and nonroutine counseling of female patients.

Results

Among 140 urologists, the majority did not routinely counsel patients about sexual orientation, partner sexual dysfunction, or referral options to sexual health services. Providers were significantly more likely to not provide routine counseling to female patients compared to male patients about the following topics: baseline sexual activity (20.6% vs 9.7%, respectively, P = 0.04), baseline sexual dysfunction (60.8% vs 20.2%, respectively, P < 0.05), the risk of sexual dysfunction after RC (20.0% vs 6.5%, respectively, P = 0.006), the potential for nerve-sparing RC (70.8% vs 35.5%, respectively, P = 0.002), and postoperative sexual health and dysfunction (42.6% vs 21.1%, respectively, P = 0.01). Overall, 41.2% of providers did not routinely discuss the potential for pelvic organ-preserving RC with sexually active female patients. Provider sex, age, practice type, urologic oncology fellowship training, years in practice, or female RC volume were not predictive of nonroutine or disparate counseling of female patients. The most common barriers to counseling female patients were older patient age (50.7%), inadequate time (47.1%), and uncertainty about baseline sexual function (37.1%).

Clinical Implications

Urologists acknowledge key deficiencies and gender disparities in sexual health counseling of patients undergoing RC.

Strengths and Limitations

Although cross-sectional, to our knowledge, this is the first study to examine provider practice patterns regarding sexual health counseling of patients undergoing RC.

Conclusion

Future efforts should be directed towards reducing barriers to sexual health counseling of patients undergoing RC to improve deficiencies and gender disparities.
Endoscopic endonasal approaches to the craniovertebral junction: The Otolaryngologist's perspective
Authors: Husain Qasim , Kim Matthew H. , Hussain Ibrahim , Anand Vijay K. , Greenfield Jeffrey P. , Schwartz Theodore H. , Kacker Ashutosh
Published: March 2020

Objective

To review indications and techniques for the endoscopic endonasal approach to the craniovertebral junction (CVJ), analyze postoperative outcomes, and discuss important technical considerations.

Methods

A retrospective analysis was performed on all patients undergoing endonasal endoscopic approaches to the CVJ from May 2007 to June 2017. Demographic information, presenting symptoms, imaging results, treatment course, postoperative functional status, and follow‐up were recorded.

Results

There was a total of 30 patients in this series, with a mean follow‐up of 11.7 months. The average age was 33.6 years (range, 5–75 years), with 18 females and 12 males. The majority of patients (n = 22, 73.3%) had Chiari malformation type 1 with basilar invagination and symptomatic cervicomedullary compression as the indication for surgery. Intraoperative cerebrospinal fluid leak (CSF) was noted in 3 cases of odontoid resection and a single case of skull base resection. There were no postoperative CSF leaks. Overall, 81% of patients resumed regular diet by post‐operative day 2 (range, 0–8 days). Severe postoperative dysphagia occurred in two cases with one requiring gastrostomy tube placement and another utilizing total parenteral nutrition for support prior to eventual gastrostomy. On average, patients were extubated by postoperative day 0.93 (range 0–3 days), with 85% extubated by postoperative day 1. A tracheotomy was required in one patient.

Conclusion

The endonasal endoscopic approach is a valuable technique for access to the CVJ with minimal disruption of respiratory and alimentary function.
Converging on Truth
Authors: Stimson James A. , Wager Emily
Published: March 2020

Much of the science of public opinion focuses on individuals, asking if they perceive or misperceive and why. Often this science will emphasize misperceptions and the psychological processes that produce them. But political debates have outcomes in the aggregate. This Element turns to a more systematic approach, emphasizing whole electorates and examining facts through a dynamic lens. It argues public opinion will converge toward truth over time and frequently finds correct views of facts grow stronger under information flow, while misperception recedes.
A single-blind clustered randomised controlled trial of daily record-keeping for reducing smoking tobacco expenditure among adult male household heads in rural Bangladesh
Authors: Fakir Adnan M. S. , Karim Afraim , Mubde Mutasim Billah , Aziz Mustahsin , Ahmad Azraf Uddin
Published: March 2020

Introduction

This study aims to assess the impact of a behavioural intervention, in the form of a self-monitoring record-keeping logbook, in reducing smoking tobacco expenditure amongst adult male household heads in rural Bangladesh.

Method

The experiment was designed as a single-blind clustered randomised controlled trial utilising two-stage random sampling. A total of 650 adult male household heads were sampled from 16 chars (riverine islands) from Gaibandha, Northern Bangladesh, with eight chars in treatment and control groups each, between November 2018 and January 2019. The intervention consisted of a logbook to record daily smoking tobacco intake for 4 weeks provided only to participants in treatment chars (n = 332) while households in control chars received nothing (n = 318).

Results

Final analysis was conducted using 222 and 210 households in the treatment and control chars respectively. The logbook intervention had a significant impact (P-value = 0.040) on reducing daily tobacco expenditure by 14% (α = 95%; CI: −0.273, −0.008) for the treatment group relative to the control group based on a difference-in-difference estimator. This is equivalent to a reduction of 20 cigarettes or 140 bidis smoked in a month.

Conclusion

Our minimal contact intervention successfully induced a reduction in smoking tobacco expenditure, which could effectively be incorporated with existing programs in the char regions of Bangladesh.
Glacial events during the last glacial termination in the Pagele valley, Qiongmu Gangri peak, southern Tibetan Plateau, and their links to oceanic and atmospheric circulation
Authors: Xu Xiangke , Yao Tandong , Xu Baiqing , Yi Chaolu , Sun Yong , Zeng Xuezhen , Dong Guocheng , Pan Baolin
Published: March 2020

During the last glacial termination, a warming trend was generally interrupted by rapid millennium-scale cold reversals, such as the Greenland (Isotope) Stadial 1 (GS-1) and GS-2a events. To understand how glaciers on the Tibetan Plateau (TP) responded to these rapid climate events, this study constrained the timing and extent of three glacial events during the late-glacial period. Specifically, using a cosmogenic 10Be exposure dating method, we dated three prominent glacial moraines (PM1, PM2, PM3) back to 15,850 ± 980, 14,140 ± 880, and 12,430 ± 790 yr in the Pagele valley, southern TP, corresponding to GS-2a, Greenland Interstadial 1 (GI-1), and GS-1, respectively. By simulating glacial extents forced by different climate scenarios, the study constrained the temperature decreases relative to present to be 2.6°C–2.9°C, ~1.6°C, and 1.4°C–1.5°C during the GS-2a, GI-1, and GS-1 periods in the region, with precipitation values of 60%–80%, ~100%, and 80%–90% of present value, respectively. Considering information from oceanic and atmospheric circulation, the study suggested that on the TP, the glacial events during the last glacial termination were well connected with the millennium-scale climate events in the North Atlantic region through the westerlies, while the Indian summer monsoon played a positive role in sustaining the glaciers under the warming climate trend.
Integrated Dating of the Construction and Restoration of the Modena Cathedral Vaults (Northern Italy): Preliminary Results
Authors: Tirelli G , Lugli S , Galli A , Hajdas I , Lindroos A , Martini M , Maspero F , Olsen J , Ringbom Å , Sibilia E , Caroselli M , Silvestri E , Panzeri L
Published: March 2020

After the last damaging earthquake in 2012, an anti-seismic reinforcement project of the cathedral of Modena was designed giving us the opportunity to investigate and date the building materials. Radiocarbon (14C), optically stimulated luminescence (OSL), and thermoluminescence (TL) dating techniques were performed on the vaults with the aim to (1) clarify the construction timing, (2) define the history of the restorations, and (3) explore the possible correlation of the main restoration works to the earthquake chronology deduced from the historic catalog. Preliminary results show that medieval older bricks were reused for most of the original construction. Only lime and non-gypsum mortar was used for the original construction in the 15th century and for later repair of damage caused by earthquakes in the 16th and 17th centuries. Gypsum mortar was used for later repair in the 18th century. The results show much stronger damage due to earthquakes than previously thought.
Exile and Linguistic Encounter: Early Modern English Convents in the Low Countries and France
Authors: Murphy Emilie K. M.
Published: March 2020

The history of religious migration and experience of exile in the early modern period has received a great deal of attention in recent years. Neglected within this scholarship, however, is sustained discussion of linguistic encounter within these often fraught transcultural and transnational interactions. This article breaks new ground by exploring the linguistic experiences of religious exiles in English convents founded in the Low Countries. Most women within English communities in exile were linguistically challenged; focusing on the creative ways these women subsequently negotiated language barriers sheds new light on female language acquisition and encounter during this period.
Tragedy at Wittenberg: Sophocles in Reformation Europe
Authors: Lazarus Micha
Published: March 2020

Amid the devastation of the Schmalkaldic War (1546–47), Philip Melanchthon and his colleagues at Wittenberg hastily compiled a Latin edition of Sophocles from fifteen years of teaching materials and sent it to Edward VI of England within weeks of his coronation. Wittenberg tragedy reconciled Aristotelian technology, Reformation politics, and Lutheran theology, offering consolation in the face of events that themselves seemed to be unfolding on a tragic stage. A crucial but neglected source of English and Continental literary thought, the Wittenberg Sophocles shaped the reception of Greek tragedy, tragic poetics, and Neo-Latin and vernacular composition throughout the sixteenth century.
(WEAK) INCIDENCE BIALGEBRAS OF MONOIDAL CATEGORIES
Authors: KRÄHMER ULRICH , ROTHERAY LUCIA
Published: March 2020

Incidence coalgebras of categories in the sense of Joni and Rota are studied, specifically cases where a monoidal product on the category turns these into (weak) bialgebras. The overlap with the theory of combinatorial Hopf algebras and that of Hopf quivers is discussed, and examples including trees, skew shapes, Milner’s bigraphs and crossed modules are considered.
The effect of iron on Trichomonas vaginalis TvCP2: a cysteine proteinase found in vaginal secretions of trichomoniasis patients
Authors: Rivera-Rivas Luis Alberto , Lorenzo-Benito Sebastián , Sánchez-Rodríguez Diana Belén , Miranda-Ozuna Jesús FT , Euceda-Padilla Esly Alejandra , Ortega-López Jaime , Chávez-Munguía Bibiana , Lagunes-Guillén Anel , Velázquez-Valassi Beatriz , Jasso-Villazul Lidia , Arroyo Rossana
Published: March 2020

Trichomonas vaginalis (Tv) induces host cell damage through cysteine proteinases (CPs) modulated by iron. An immunoproteomic analysis showed that trichomoniasis patient sera recognize various CPs, also some of them are present in vaginal washes (VWs). Thus, the goal of this work was to determine whether TvCP2 is expressed during infection and to assess the effect of iron on TvCP2 expression, localization and contribution to in vitro cellular damage. Western-blotting (WB) assays using TvCP2r and vaginitis patient serum samples showed that 6/9 Tv (+) but none of the Tv (−) patient sera recognized TvCP2r. WB using an anti-TvCP2r antibody and VWs from the same patients showed that in all of the Tv (+) but none of the Tv (−) VWs, the anti-TvCP2r antibody detected a 27 kDa protein band that corresponded to the mature TvCP2, which was confirmed by mass spectrometry analysis. Iron decreased the amount of TvCP2 mRNA and the protein localized on the parasite surface and cytoplasmic vesicles concomitant with the cytotoxic effect of TvCP2 on HeLa cells. Parasites pretreated with the anti-TvCP2r antibody also showed reduced levels of cytotoxicity and apoptosis induction in HeLa cell monolayers. In conclusion, these results show that TvCP2 is expressed during trichomonal infection and plays an important role in the in vitro HeLa cell cytotoxic damage under iron-restricted conditions.
The jumping to conclusions reasoning bias as a cognitive factor contributing to psychosis progression and persistence: findings from NEMESIS-2
Authors: Rauschenberg Christian , Reininghaus Ulrich , ten Have Margreet , de Graaf Ron , van Dorsselaer Saskia , Simons Claudia J. P. , Gunther Nicole , Henquet Cécile , Pries Lotta-Katrin , Guloksuz Sinan , Bak Maarten , van Os Jim
Published: March 2020

Background

Contemporary models of psychosis implicate the importance of affective dysregulation and cognitive factors (e.g. biases and schemas) in the development and maintenance of psychotic symptoms, but studies testing proposed mechanisms remain limited. This study, uniquely using a prospective design, investigated whether the jumping to conclusions (JTC) reasoning bias contributes to psychosis progression and persistence.

Methods

Data were derived from the second Netherlands Mental Health Survey and Incidence Study (NEMESIS-2). The Composite International Diagnostic Interview and an add-on instrument were used to assess affective dysregulation (i.e. depression, anxiety and mania) and psychotic experiences (PEs), respectively. The beads task was used to assess JTC bias. Time series analyses were conducted using data from T1 and T2 (N = 8666), excluding individuals who reported high psychosis levels at T0.

Results

Although the prospective design resulted in low statistical power, the findings suggest that, compared to those without symptoms, individuals with lifetime affective dysregulation were more likely to progress from low/moderate psychosis levels (state of ‘aberrant salience’, one or two PEs) at T1 to high psychosis levels (‘frank psychosis’, three or more PEs or psychosis-related help-seeking behaviour) at T2 if the JTC bias was present [adj. relative risk ratio (RRR): 3.8, 95% confidence interval (CI) 0.8–18.6, p = 0.101]. Similarly, the JTC bias contributed to the persistence of high psychosis levels (adj. RRR: 12.7, 95% CI 0.7–239.6, p = 0.091).

Conclusions

We found some evidence that the JTC bias may contribute to psychosis progression and persistence in individuals with affective dysregulation. However, well-powered prospective studies are needed to replicate these findings.
Sustained benefit of cognitive behaviour therapy for health anxiety in medical patients (CHAMP) over 8 years: a randomised-controlled trial
Authors: Tyrer P. , Wang D. , Crawford M. , Dupont S. , Cooper S. , Nourmand S. , Lazarevic V. , Philip A. , Tyrer H.
Published: March 2020

Background

Health anxiety is an under-recognised but a frequent cause of distress. It is particularly common in general hospitals.

Methods

We carried out an 8-year follow-up of medical out-patients with health anxiety (hypochondriasis) enrolled in a randomised-controlled trial in five general hospitals in London, Middlesex and Nottinghamshire. Randomisation was to a mean of six sessions of cognitive behaviour therapy adapted for health anxiety (CBT-HA) or to standard care in the clinics. The primary outcome was a change in score on the Short Health Anxiety Inventory, with generalised anxiety and depression as secondary outcomes. Of 444 patients aged 16–75 years seen in cardiology, endocrinology, gastroenterology, neurology and respiratory medicine clinics, 306 (68.9%) were followed-up 8 years after randomisation, including 36 who had died. The study is registered with controlled-trials.com, ISRCTN14565822.

Results

There was a significant difference in the HAI score in favour of CBT-HA over standard care after 8 years [1.83, 95% confidence interval (CI) 0.25–3.40, p = 0.023], between group differences in generalised anxiety were less (0.54, 95% CI −0.29 to 1.36), p = 0.20, ns), but those for depression were greater at 8 years (1.22, 95% CI 0.42–2.01, p < 0.003) in CBT-HA than in standard care, most in standard care satisfying the criteria for clinical depression. Those seen by nurse therapists and in cardiology and gastrointestinal clinics achieved the greatest gains with CBT-HA, with greater improvement in both symptoms and social function.

Conclusions

CBT-HA is a highly long-term effective treatment for pathological health anxiety with long-term benefits. Standard care for health anxiety in medical clinics promotes depression. Nurse therapists are effective practitioners.
Double elevation: Autonomous weapons and the search for an irreducible law of war
Authors: Kalpouzos Ioannis
Published: March 2020

What should be the role of law in response to the spread of artificial intelligence in war? Fuelled by both public and private investment, military technology is accelerating towards increasingly autonomous weapons, as well as the merging of humans and machines. Contrary to much of the contemporary debate, this is not a paradigm change; it is the intensification of a central feature in the relationship between technology and war: double elevation, above one’s enemy and above oneself. Elevation above one’s enemy aspires to spatial, moral, and civilizational distance. Elevation above oneself reflects a belief in rational improvement that sees humanity as the cause of inhumanity and de-humanization as our best chance for humanization. The distance of double elevation is served by the mechanization of judgement. To the extent that judgement is seen as reducible to algorithm, law becomes the handmaiden of mechanization. In response, neither a focus on questions of compatibility nor a call for a ‘ban on killer robots’ help in articulating a meaningful role for law. Instead, I argue that we should turn to a long-standing philosophical critique of artificial intelligence, which highlights not the threat of omniscience, but that of impoverished intelligence. Therefore, if there is to be a meaningful role for law in resisting double elevation, it should be law encompassing subjectivity, emotion and imagination, law irreducible to algorithm, a law of war that appreciates situated judgement in the wielding of violence for the collective.
Animal agriculture exposures among Minnesota residents with zoonotic enteric infections, 2012–2016
Authors: Klumb CA , Scheftel JM , Smith KE
Published: March 2020

Prospective, population-based surveillance to systematically ascertain exposures to food production animals or their environments among Minnesota residents with sporadic, domestically acquired, laboratory-confirmed enteric zoonotic pathogen infections was conducted from 2012 through 2016. Twenty-three percent (n = 1708) of the 7560 enteric disease cases in the study reported an animal agriculture exposure in their incubation period, including 60% (344/571) of Cryptosporidium parvum cases, 28% (934/3391) of Campylobacter cases, 22% (85/383) of Shiga toxin-producing Escherichia coli (STEC) O157 cases, 16% (83/521) of non-O157 STEC cases, 10% (253/2575) of non-typhoidal Salmonella enterica cases and 8% (9/119) of Yersinia enterocolitica cases. Living and/or working on a farm accounted for 61% of cases with an agricultural exposure, followed by visiting a private farm (29% of cases) and visiting a public animal agriculture venue (10% of cases). Cattle were the most common animal type in agricultural exposures, reported by 72% of cases. The estimated cumulative incidence of zoonotic enteric infections for people who live and/or work on farms with food production animals in Minnesota during 2012–2016 was 147 per 10 000 population, vs. 18.5 per 10 000 for other Minnesotans. The burden of enteric zoonoses among people with animal agriculture exposures appears to be far greater than previously appreciated.
Effect handlers via generalised continuations
Authors: HILLERSTRÖM DANIEL , LINDLEY SAM , ATKEY ROBERT
Published: March 2020

Plotkin and Pretnar’s effect handlers offer a versatile abstraction for modular programming with user-defined effects. This paper focuses on foundations for implementing effect handlers, for the three different kinds of effect handlers that have been proposed in the literature: deep, shallow, and parameterised. Traditional deep handlers are defined by folds over computation trees and are the original construct proposed by Plotkin and Pretnar. Shallow handlers are defined by case splits (rather than folds) over computation trees. Parameterised handlers are deep handlers extended with a state value that is threaded through the folds over computation trees. We formulate the extensions both directly and via encodings in terms of deep handlers and illustrate how the direct implementations avoid the generation of unnecessary closures. We give two distinct foundational implementations of all the kinds of handlers we consider: a continuation-passing style (CPS) transformation and a CEK-style abstract machine. In both cases, the key ingredient is a generalisation of the notion of continuation to accommodate stacks of effect handlers. We obtain our CPS translation through a series of refinements as follows. We begin with a first-order CPS translation into untyped lambda calculus which manages a stack of continuations and handlers as a curried sequence of arguments. We then refine the initial CPS translation by uncurrying it to yield a properly tail-recursive translation and then moving towards more and more intensional representations of continuations in order to support different kinds of effect handlers. Finally, we make the translation higher order in order to contract administrative redexes at translation time. Our abstract machine design then uses the same generalised continuation representation as the CPS translation. We have implemented both the abstract machine and the CPS transformation (plus extensions) as backends for the Links web programming language.
What Will the Weather Do? Forecasting Flood Losses Based on Oscillation Indices
Authors: Guimarães Nobre Gabriela , de Moel Hans , Giuliani Matteo , Bischiniotis Konstantinos , Aerts Jeroen C. J. H. , Ward Philip J.
Published: March 2020

Atmospheric oscillations are known to drive the large‐scale variability of hydrometeorological extremes in Europe, which can trigger flood events and losses. However, to date there are no studies that have assessed the combined influence of different large‐scale atmospheric oscillations on the probabilities of flood losses occurring. Therefore, in this study we examine the relationship between five indices of atmospheric oscillation and four classes of flood losses probabilities at subregional European scales. In doing so, we examine different combinations of atmospheric oscillations, both synchronous and seasonally lagged. By applying logistic regressions, we aim to identify regions and seasons where probabilities of flood losses occurring can be estimated by indices of atmospheric oscillation with higher skill than historical probabilities. We show that classes of flood losses can be predicted by synchronous indices of atmospheric oscillation and that in some seasons and regions lagged relationships may exist between the indices of atmospheric oscillation and the probability of flood losses. Furthermore, we find that some models generate increased (or decreased) probability of flood losses occurring when the indices are at their extreme positive or negative phases. A better understanding of the effects of atmospheric oscillations on the likelihood of flood losses occurring represents a step forward in achieving flood resilience in Europe. For instance, improved early predictions of the indices that represent such atmospheric oscillations, or the evidence of a lagged relationship between their teleconnections and floods, can significantly contribute to mitigating the socioeconomic burden of floods.
Using Multiple Signatures to Improve Accuracy of Substorm Identification
Authors: Haiducek John D. , Welling Daniel T. , Morley Steven K. , Ganushkina Natalia Yu , Chu Xiangning
Published: March 2020

We have developed a new procedure for combining lists of substorm onset times from multiple sources. We apply this procedure to observational data and to magnetohydrodynamic (MHD) model output from 1–31 January 2005. We show that this procedure is capable of rejecting false positive identifications and filling data gaps that appear in individual lists. The resulting combined onset lists produce a waiting time distribution that is comparable to previously published results, and superposed epoch analyses of the solar wind driving conditions and magnetospheric response during the resulting onset times are also comparable to previous results. Comparison of the substorm onset list from the MHD model to that obtained from observational data reveals that the MHD model reproduces many of the characteristic features of the observed substorms, in terms of solar wind driving, magnetospheric response, and waiting time distribution. Heidke skill scores show that the MHD model has statistically significant skill in predicting substorm onset times.
An Exoplanet with Evolving Clouds of Salts
Authors: Redd Nola
Published: March 2020

Clouds form and dissipate on a gas giant orbiting a Sun-like star.
New England Forests Were Historically Shaped by Climate, Not People
Authors: Fritts Rachel
Published: March 2020

A first-of-its-kind study combining paleoecology and archeology indicates that the New England landscape was not actively managed with fire prior to European arrival.
Hot White Dwarfs May Reveal Cold Gas Giants
Authors: Redd Nola
Published: March 2020

The gaseous atmospheres of giant planets may evaporate and accrete onto the dense surfaces of white dwarfs, providing astronomers a new way to detect hidden exoplanets.
Combining AI and Analog Forecasting to Predict Extreme Weather
Authors: Sima Richard
Published: March 2020

New deep learning technique brings an obsolete forecasting method “back to life” to predict extreme weather events.
Could Wildfire Ash Feed the Ocean’s Tiniest Life-Forms?
Authors: Duncombe Jenessa
Published: March 2020

Ash falling on the ocean after a wildfire could fuel plankton growth.
Nuclear War Would Spawn a “Nuclear” El Ni�o
Authors: Duncombe Jenessa
Published: March 2020

A jolt to the climate system provided by nuclear war could spur an El Ni�o like we’ve never seen before.
Snapping Shrimp Pump Up the Volume in Warmer Water
Authors: Kornei Katherine
Published: March 2020

As the ocean warms because of climate change, the louder din could mask other marine animals’ calls used to navigate, forage, and find mates.
Patterns and Drivers of Carbon Dioxide Concentrations in Aquatic Ecosystems of the Arctic Coastal Tundra
Authors: Lougheed V. L. , Tweedie C. E. , Andresen C. G. , Armendariz A. M. , Escarzaga S. M. , Tarin G.
Published: March 2020

Multiple aquatic ecosystems (pond, lake, river, lagoon, and ocean) on the Arctic Coastal Plain near Utqiaġvik, Alaska, USA, were visited to determine their relative atmospheric CO2 flux and how this may have changed over time. The nearshore coastal waters and large freshwater lakes were small sources of atmospheric CO2, whereas smaller waterbodies were substantial sources. pCO2 was linked to dissolved organic carbon concentrations across broad spatial and temporal scales, with greater concentrations found in smaller freshwater systems (i.e., ponds and rivers). On a day‐to‐day basis, water temperatures appeared to be the strongest driver of pCO2 levels in tundra ponds, where warmer temperatures likely stimulated microbial mineralization of carbon in both aquatic and hydrologically linked terrestrial environments. Large rainfall events, which may lead to inflow of carbon‐rich groundwater into these ponds, also were associated with increased daily average pCO2. Based on comparison to historical data, we estimate that CO2 concentrations in tundra ponds have increased more than 1.8 times over the past 40 years. Quantifying CO2 flux from these abundant aquatic ecosystems on the Arctic Coastal Plain and elsewhere in the high northern latitudes will likely have important implications for furthering understanding of landscape‐level and nearshore carbon dynamics in the Arctic.
Thank You to Our 2019 Reviewers
Authors: Huber Matthew , Röhl Ursula (Ulla)
Published: March 2020

Key Points

Thank you to the 351 reviewers who submitted 486 reviews in the journal last year.
Tumour-agnostic drugs in paediatric cancers
Authors: Chisholm Julia C. , Carceller Fernando , Marshall Lynley V.
Published: March 2020

The recognition that new cancer drugs can be truly tumour-agnostic based on mechanism-of-action is important for paediatric cancers, where access to novel targeted therapies developed for adult indications has sometimes been problematic. The recently approved drug larotrectinib is an excellent case study of the development of a tumour-agnostic drug relevant to children.
Prohibitin 2 deficiency impairs cardiac fatty acid oxidation and causes heart failure
Authors: Wu Dechao , Jian Chongshu , Peng Qi , Hou Tingting , Wu Keling , Shang Bizhi , Zhao Minglei , Wang Yanru , Zheng Wen , Ma Qi , Li Chuan-Yun , Cheng Heping , Wang Xianhua , Zhao Ling
Published: March 2020

Fatty acids are the most major substrate source for adult cardiac energy generation. Prohibitin 2 (PHB2), a highly conserved protein located in mitochondrial inner membrane, plays key roles in cellular energy metabolic homeostasis. However, its functions in regulating cardiac fatty acid metabolism have remained largely unknown. Our study demonstrates that cardiac-specific knockout of Phb2 leads to accumulation of lipid droplets and causes heart failure. Mechanistically, ablation of PHB2 impairs cardiac fatty acid oxidation (FAO) through downregulating carnitine palmitoyltransferase1b (CPT1b), a rate-limiting enzyme of cardiac mitochondrial FAO. Moreover, overexpression of CPT1b alleviates impaired FAO in PHB2-deficient cardiomyocytes. Thus, our study provides direct evidence for the link between PHB2 and cardiac fatty acid metabolism. Our study points out that PHB2 is a potential FAO regulator in cardiac mitochondrial inner membrane, as well as the connection between PHB2 and CPT1b and their relationships to cardiac pathology especially to cardiac fatty acid metabolic disorder.
Can a simple topological-constraints-based model predict the initial dissolution rate of borosilicate and aluminosilicate glasses?
Authors: Gin Stéphane , Wang Mengyi , Bisbrouck Nicolas , Taron Mélanie , Lu Xiaonan , Deng Lu , Angeli Frédéric , Charpentier Thibault , Delaye Jean-Marc , Du Jincheng , Bauchy Mathieu
Published: March 2020

Tuning glass composition to obtain targeted properties generally relies on empirical approaches. However, a deep understanding of the physical and chemical mechanisms linking glass composition to its structure and properties would enable developing reliable predictive models. Indeed, although empirical models are usually able to interpolate composition–property relationships within a given compositional envelope, they often fail at extrapolating predictions far from their training domain. Here, as an alternative route to empirical models, we show that a structural descriptor based on the number of topological constraints per atom can be used to predict the initial dissolution rate of aluminosilicate and borosilicate glasses after being parameterized on different families of glasses (specific series of borosilicate glasses). Sixteen glasses belonging to these families were studied and their initial dissolution rates were determined at 90 °C and pH90 °C = 9, covering rates spanning over 5 orders of magnitude. The model based on topological constraints was trained based on seven select borosilicate glasses (R2 = 0.997) and used to predict the dissolution rate of nine additional borosilicate and aluminosilicate glasses. We show that, provided that corrections are made for high alkali content glasses that dissolve incongruently (preferential release of Na), the model gives reasonable predictions, even far from its training domain.