bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discounts for Early Plea
Authors: Dalton Bartholomew , Liggins Caroline 
Published: October 2024

Abstract
This chapter evaluates the provisions on discounts for early plea, including the relevant case law. A court must discount a sentence in return for a guilty plea. A magistrates’ court may impose a maximum sentence as an alternative to committing the case for sentence to the Crown Court. A full discount must be given even if the prosecution case is overwhelming. The amount of discount will depend upon the timing of the plea. A one-third reduction is only available, subject to exceptions, when a guilty plea is indicated at the first hearing whether the case proceeds in the magistrates’ or Crown Court. Thereafter the maximum is one-quarter, reducing to 10 per cent if the plea is entered at the time of trial. The discount is separate from any other reduction, which should be taken into account before the discount for guilty plea is applied. The chapter then looks at the determination of the level of sentence reduction, its application, and exceptions.
Disqualification from Driving
Authors: Dalton Bartholomew , Liggins Caroline 
Published: October 2024

Abstract
This chapter details the provision on disqualification from driving. Disqualification may arise in one of five ways: (1) offence carrying obligatory disqualification; (2) offence carrying discretionary disqualification; (3) as a result of accumulating 12 or more penalty points; (4) as a result of conviction for any offence, or an offence where a vehicle was used for crime; or (5) as a result of a ‘new driver’ accumulating six penalty points. Where disqualification is imposed, the licence should be endorsed, but not with any penalty points in respect of that offence or other offences perpetrated on the same occasion. The normal practice is to impose no separate penalty on the related crimes, but disqualify alone on the main crime. Section 39 of the Road Traffic Offenders Act (RTOA) 1988 allows for applications to suspend a disqualification pending appeal. The chapter also considers interim disqualification and disqualification with an immediate custodial sentence.
Mental Health Disposals
Authors: Dalton Bartholomew , Liggins Caroline 
Published: October 2024

Abstract
This chapter explores the provision of mental health disposals. The Sentencing Council has issued a guideline on sentencing offenders with mental disorders, developmental disorders, or neurological impairments. The fact that an offender has an impairment or disorder should always be considered by the court but will not necessarily have an impact on sentencing. Culpability may be reduced if an offender was at the time of the offence suffering from an impairment or disorder. The chapter then looks at the provision on guardianship and hospital orders under section 37 of the Mental Health Act 2983. It also considers the power of the magistrates’ court, under section 35 of the Mental Health Act 1983, to remand an accused person to a hospital for a report on their mental condition. Finally, the chapter describes the power of the magistrates’ court to commit for restriction order under section 43 of the Mental Health Act 1983.
Restraining Order
Authors: Dalton Bartholomew , Liggins Caroline 
Published: October 2024

Abstract
This chapter sets out the provisions in relation to restraining orders. Under the Sentencing Act (SA) 2020, a court may impose a restraining order following conviction and under the Protection from Harassment Act 1997, on acquittal. When a prosecutor seeks a restraining order, Criminal Procedure Rules Part 31.3 requires that the prosecutor must serve a draft order on the court officer and on the defendant as soon as practicable (without waiting for the verdict). The draft order must specify those prohibitions which, if the defendant is convicted, the prosecutor proposes for the purpose of protecting a person from conduct which amounts to harassment or will cause fear of violence, or those prohibitions which, if the defendant is acquitted, the prosecutor proposes as necessary to protect a person from harassment by the defendant. A restraining order cannot be made against someone who has been found unfit to plead as that finding is neither a conviction nor an acquittal.
Explanatory Pluralism in Normative Ethics
Authors: Väyrynen Pekka 
Published: October 2024

AbstractSome theorists of normative explanation argue that we can make sense of debates between first-order moral theories such as consequentialism and its rivals only if we understand their explanations of why the right acts are right and the wrong acts are wrong as generative grounding explanations. Others argue that the standard form of normative explanation is, instead, some kind of unification. Neither sort of explanatory monism can account for all the explanations of particular moral facts that moral theorists state and defend. This chapter argues that we can do better if we accept normative explanatory pluralism, the view that at least some particular moral facts have more than one type of correct complete explanation. Such pluralism is supported by what goes on in actual moral inquiry, parallels an independently plausible form of pluralism about scientific explanation, and can offer principled responses to central objections.
Immunogenicity to herpes zoster recombinant subunit vaccine in immune-mediated rheumatic patients under treatment with JAK inhibitors
Authors: Sieiro Santos Cristiana , Herrero Juan Garcia , Ordas Martínez Jose , Álvarez Castro Carolina , López Robles Alejandra , Colindres Ronald , Martín Estefanía Robles , Sahagun Ana M , Ruiz de Morales Jose G 
Published: October 2024

Abstract

Objectives
Patients with immune-mediated rheumatic diseases (IMRDs) face an elevated risk of varicella-zoster virus infection (VZV) and herpes zoster (HZ). Treatment with immunosuppressors further increases the risk. A new recently approved adjuvant recombinant inactive vaccine offers safe protection against HZ. However, limited data exist on the efficacy of this new vaccine in patients with IMRDs treated with JAK inhibitors (JAK-i). We aimed to characterize B- and T-cell immune responses elicited by the HZ recombinant subunit vaccine in patients with IMRDs under treatment with JAK-i, and to identify factors that might be associated with reduced immunogenicity, and therefore reduced protection.

Methods
We investigated humoral and cellular CD4 and CD8 immune responses following a two-dose regimen of the recombinant inactive vaccine in 43 patients with rheumatic diseases treated with different JAK-i. The responses were compared with age, gender and disease-matched healthy controls.

Results
Patients with IMRDs treated with JAK-i showed reduced seroconversion rate (63% vs. 100% and lower VZV IgG titres (1222 ± 411 vs. 3048 ± 556, P &lt; 0.0001) as compared with healthy controls. Functional T CD4 (IL-2 plus IFN-γ secretion) and T CD8 (granzyme A and/or granzyme B secretion) immune responses were also significantly diminished in IMRD patients. Negative correlation was found between VZV antibody titres and age, specific treatments (baricitinib, tofacitinib, upadacitinib), cumulative MTX and glucocorticoid doses, history of multiple DMARDs and treatment duration with JAK-i. Functional T-CD4 responses but not functional T-CD8 responses also showed similar negative correlations. Positive associations were observed between functional T-CD4 and T-CD8 responses.

Conclusions
Our study provides valuable insights into the immune responses elicited by the recombinant inactive vaccine in patients with IMRDs treated with JAK-i. In these patients we have observed a broad impact on the adaptive humoral and cellular immune responses, suggesting a potential reduction in protection against HZ infection and VZV reactivation.
The place of JAK inhibitors in systemic juvenile idiopathic arthritis with lung disease: French experience
Authors: Côte Gaëlle , Quartier Pierre , Belot Alexandre , Melki Isabelle , Hentgen Véronique , Merlin Etienne 
Published: October 2024

Abstract

Objectives
A new form of systemic juvenile idiopathic arthritis (SJIA) with associated lung disease (SJIA-LD) has recently been described. Multiple lines of treatment have failed to yield satisfactory results for this disorder. Janus kinase inhibitors (JAKis) have recently been approved for the treatment of JIA, but clinical evidence of their efficacy in SJIA-LD is still weak. Here we describe and assess real-life experience of SJIA-LD treatment with JAKis in France.

Methods
This is a retrospective study based on information gathered from patients’ medical records. Systemic and pulmonary symptoms and biological data including CRP, ferritin, IL-18, chest CT scan and functional respiratory tests were collected.

Results
Eight patients with SJIA-LD were identified in French paediatric rheumatology centres. All received at least one JAKi (baricitinib, ruxolitinib and/or tofacitinib). Complete disease control was obtained in four patients. Steroids were tapered in four patients and stopped in two. Three patients presented an episode of macrophage activation syndrome (MAS) shortly after anti-IL-1s were stopped when JAKis were introduced. Two patients had other serious side effects (viral reactivation—EBV, BK virus, cytopenia). At last follow-up, one patient had died from severe MAS, two patients had undergone haematopoietic stem cell transplantation, four were in complete response (two of them free of steroids), and one in partial response with JAKis. Lung response to JAKi was not clearly linked to disease duration.

Conclusion
JAKis offer another therapeutic option for patients with SJIA-LD. However, the risk of MAS argues for caution about stopping anti-IL-1s when introducing JAKis. Tolerance needs careful monitoring in larger studies..
Increased neutrophil extracellular traps caused by diet‐induced obesity delay fracture healing
Authors: Zhao Xuan , Wang Qijun , Wang Wei , Lu Shibao 
Published: October 2024

AbstractObesity, recognized as a risk factor for nonunion, detrimentally impacts bone health, with significant physical and economic repercussions for affected individuals. Nevertheless, the precise pathomechanisms by which obesity impairs fracture healing remain insufficiently understood. Multiple studies have identified neutrophil granulocytes as key players in the systemic immune response, being the predominant immune cells in early fracture hematomas. This study identified a previously unreported critical period for neutrophil infiltration into the callus. In vivo experiments demonstrated that diet‐induced obesity (DIO) mice showed earlier neutrophil infiltration, along with increased formation of neutrophil extracellular traps (NETs), compared to control mice during the endochondral phase of fracture repair. Furthermore, Padi4 knockout was found to reduce NET formation and mitigate the fracture healing delays caused by high‐fat diets. Mechanistically, in vitro analyses revealed that NETs, by activating NLRP3 inflammasomes, inhibited the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and concurrently promoted M1‐like macrophage polarization. These findings establish a connection between NET formation during the endochondral phase and delayed fracture healing, suggesting that targeting NETs could serve as a promising therapeutic approach for addressing obesity‐induced delays in fracture recovery.
The Living Lab at Home: Feasibility and Acceptability of Multimodal In-Home Data Collection Among Youth Across the Developmental Spectrum
Authors: Boerner Katelynn E. , Dudarev Veronica , Pearl-Dowler Leora , Wharton Marie-Noelle , Siden Harold , Holsti Liisa , Oberlander Tim F. 
Published: October 2024

ABSTRACT

Objective:
Dynamic, real-time, in-home methods of data collection are increasingly common in child health research. However, these methods are rarely cocreated or used with families of youth with developmental disabilities. We aimed to determine the feasibility of codesigned methods for in-home data collection for youth across the developmental spectrum.

Methods:
Sixteen youth (14–18 years) with autism spectrum disorder, cerebral palsy, and/or chronic pain completed 14 days of data collection, wearing an accelerometer, answering Ecological Momentary Assessment (EMA) questionnaires, and collecting salivary cortisol samples. Participants completed a poststudy interview regarding their experiences. Data were analyzed for feasibility, quantity, and quality.

Results:
At least 1 EMA response was provided on 73% of days, with 54% of the total number of administered prompts answered before the next prompt arrived. In total, 77% of participants wore the accelerometer ≥10 hours for at least 7 days. Adherence to 8-day saliva sampling after accounting for protocol violations and dry samples was 28%. No significant adverse events were reported aside from mild emotional distress (25%). Families reported generally high satisfaction, willingness to participate again, and acceptability, with moderate burden and interference. Qualitative interviews described: (1) the research question's value to the family as a motivator of engagement; (2) in-home data collection is not a passive or neutral experience; (3) personalized approaches and context are important to families; and (4) a clear need for continued iteration and engagement.

Conclusion:
In-home multimodal data collection is potentially feasible for families across the developmental spectrum but requires iteration based on family feedback to increase adherence.
A Demographic Description of Children and Adolescents With Concomitant Autism and Anxiety Along With a Comparison of Receipt of Psychological Services
Authors: Salt Elizabeth , Wiggins Amanda T. , Toupin David N. , Parks Emma , Okoli Chizimuzo , Rayens Mary Kay 
Published: October 2024

Objective:
(1) Evaluate differences in demographic distributions between those with autism alone and those with autism concomitant with anxiety and (2) assess demographic factors associated with receipt of psychological therapy in patients with autism.

Methods:
Using deidentified health care claims data, we extracted all encounters among children with the International Classification of Diseases-10-CM for Autism Spectrum Disorder (F84) and flagged those with concomitant anxiety (F41.9). Extracted data included age, sex, race, ethnicity, insurance status, and Rural-Urban Continuum Codes. Current procedural terminology codes for psychological services were extracted. Data were analyzed using Mann–Whitney U tests, χ2 tests of association, and logistic regression.

Results:
Demographic differences between children/adolescents with autism alone versus autism concomitant with anxiety were noted for age, sex, and race/ethnicity, with a greater prevalence of autism/anxiety identified in older-aged children and children identifying as female and non-Hispanic White residing in an urban area. While 21% of those included in this study had received psychotherapy, the percentages within the autism only and autism/anxiety groups were 12% and 50%, respectively (p < 0.001). Children/adolescents who were older age quartile, resided in an urban residence, and with a concomitant diagnosis of anxiety were more likely to receive psychological services, while non-Hispanic Other were less likely to, compared with the reference of non-Hispanic White.

Conclusion:
We identified demographic disparities in the diagnosis of autism versus autism with concomitant anxiety, including age, sex, race/ethnicity, and residence location. Age quartile, urban location, and concomitant anxiety were associated with increased likelihood of receipt of psychological services.
Evaluation of Effective Half-Life and Its Impact on Time to Steady State for Oral MeltDose Tacrolimus (LCPT) in De Novo Kidney Transplant Recipients
Authors: Momper Jeremiah D. , Venkataramanan Raman , Jantz Arin S. , Cibrik Diane M. , Birdwell Kelly , Nguyen Tk , Masters Brian M. , Patel Samir J. 
Published: October 2024

Background:
For extended-release drug formulations, effective half-life (t1/2eff) is a relevant pharmacokinetic parameter to inform dosing strategies and time to reach steady state. Tacrolimus, an immunosuppressant commonly used for the prophylaxis of organ rejection in transplant patients, is available as both immediate- and extended-release formulations. To the best of our knowledge, the t1/2eff of tacrolimus from these different formulations has not yet been assessed. The objective of this study was to characterize the t1/2eff and terminal half-life (t1/2z) of an extended-release once-daily tacrolimus formulation (LCPT) and twice-daily immediate-release tacrolimus (IR-Tac).

Methods:
A noncompartmental analysis of pharmacokinetic data obtained from a phase 2 study in de novo kidney transplant recipients receiving either LCPT or IR-Tac was conducted. Intensive blood sampling was performed on days 1, 7, and 14, and tacrolimus whole blood concentrations were measured using a validated liquid chromatography with tandem mass spectrometry method. T1/2eff was estimated using within-participant accumulation ratios. T1/2z was estimated by linear regression of the terminal phase of the concentration versus time profile.

Results:
The median accumulation ratios of LCPT and IR-Tac on day 14 were 3.18 and 2.06, respectively.
The median (interquartile range; IQR) t1/2eff for LCPT at day 14 of dosing was 48.4 (37.4–77.9) hours, whereas the t1/2z was 20.3 (17.6–22.9) hours. For IR-Tac, the median (IQR) t1/2eff and t1/2z on day 14 were 12.5 (8.8–23.0) hours and 12.2 (9.2–15.7) hours, respectively.

Conclusions:
Consistent with its prolonged release of tacrolimus, LCPT demonstrated a higher accumulation ratio and a longer t1/2eff compared with IR-Tac. These findings underscore the pharmacokinetic differences between different drug formulations of the same moiety and may help inform dose adjustments for LCPT in kidney transplantation.
Superior cervical ganglionectomy attenuates vascular remodeling in spontaneously hypertensive rats
Authors: Wang Jing-Xiao , Xu Xiao-Yu , Wang Yi-Ming , Chen Ai-Dong , Li Yue-Hua , Zhu Guo-Qing , Xiong Xiao-Qing 
Published: October 2024

Background:
Sympathetic hyperactivity contributes to the pathogenesis of hypertension. However, it is unclear whether the excessive sympathetic activity is an independent and crucial factor for vascular remodeling in hypertension. This study focused on the effect of local sympathetic denervation with superior cervical ganglionectomy (SCGx) on vascular remodeling.

Methods:
Surgical bilateral SCGx was performed in 9-week-old male Wistar−Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Control rats received sham-operation without SCGx. All measurements were made 4 weeks after the surgery.

Results:
The effectiveness of SCGx was confirmed by the eye features of Horner syndrome, greatly reduced tyrosine hydroxylase (TH) contents in the superior cervical ganglion (SCG)-innervated arteries in the head. Although SCGx had no significant effects on blood pressure and heart rate in WKY and SHR, it attenuated vascular remodeling of facial artery and superficial temporal artery in SHR, two representative SCG-innervated extracranial arteries, without significant effects on non-SCG-innervated thoracic aorta and mesenteric artery. SCGx-treated SHR had more auricular blood flow and retina microvasculature than sham-operated SHR. However, SCGx had only a mild effect in attenuating the vascular remodeling of basilar artery and middle cerebral artery, two representative SCG-innervated intracranial arteries, in SHR. SCGx-treated SHR exhibited upregulation of α-smooth muscle actin, downregulation of proliferating cell nuclear antigen, and attenuation of oxidative stress and inflammation in facial artery and superficial temporal artery.

Conclusions:
Sympathetic denervation by SCGx in SHR attenuated local vascular remodeling, suggesting that sympathetic overactivity is a crucial pathogenic factor of vascular remodeling in SHR.
The incremental predictive value of arterial stiffness over SCORE2 in the setting of primary cardiovascular prevention: a 6-year follow-up study
Authors: Ikonomidis Ignatios , Thymis John , Georgiopoulos Georgios , Pavlidis George , Katogiannis Konstantinos , Kostelli Gavriella , Vlastos Dimitrios , Plotas Panagiotis , Triantafyllidi Helen , Delialis Dimitrios , Mavraganis Georgios , Lambadiari Vaia , Stamatelopoulos Kimon 
Published: October 2024

Aim:
Arterial stiffness hallmarks age-related cardiovascular diseases, precedes their onset and strongly links to accelerated disease progression. However, whether carotid-to-femoral pulse wave velocity (PWV), a proxy of arterial stiffness, predicts cardiovascular risk over and above SCORE2, a newly introduced risk score remains to be investigated.

Methods:
We measured PWV among 747 individuals without established atheromatosis. Study participants were followed up over a 6-year period for the incidence of cardiovascular events [[MACE)-cardiovascular mortality, stroke and myocardial infarction].

Results:
PWV emerged as an independent and additive predictor of first cardiovascular events when added in a model encompassing SCORE2 (hazard ratio = 1.10; 95% confidence interval (95% CI) = 1.07–1.14; P < 0.001, Brier score changed from 0.073 (0.060–0.086) to 0.067 (0.055–0.081); P < 0.001, c-statistic increased from 0.71 to 0.75; P = 0.017; likelihood ratio: 20.22; P < 0.001; the overall net reclassification improvement (NRI): 0.577; P < 0.001, AICc changed from 697.81 to 679.60; BIC changed from 702.42 to 688.82]. An increase in PWV predicted a greater risk of future MACEs additively to conventional risk factors (P < 0.05). We performed Kaplan-Meier survival analysis for the tertiles of PWV [first tertile < 8.04 m/s; the second tertile: (8.04–10 m/s); the third tertile: (10–17.10 m/s); (P < 0.05 for all comparisons between the tertiles). PWV tertiles also predicted MACE when added to SCORE2 [for the second tertile: hazard ratio: 5.87 (95% CI: 1.73–19.92); P = 0.004 and for the third tertile: hazard ratio: 9.69 (95% CI: 2.97–31.55); P < 0.001 with the respective change of c-statistic from 0.739 to 0.772; P = 0.012 and continuous NRI = 0.598].

Conclusion:
PWV confers additive prognostic value to the newly introduced SCORE2 for adverse outcome in primary prevention.