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Vivian is a cosmopolitan Taiwanese-American tourist who often escapes her busy life in London through adventure and travel. Johnny is a fifteen year old Irish teenager, growing up in a family where crime is customary, violence is necessary, and everything and anyone is yours for the taking. Their paths collide one afternoon in West Belfast, culminating in a horrific act of violence. Vivian tries to recapture the woman she was, as she struggles with a culture and judicial system that treats assault victims as less than human. Johnny flees to his transitory Irish clan, but is forced to confront the chain of events leading up to the attack. When Johnny is finally brought to reckon for his crimes, Vivian learns that justice is neither as swift nor as fair as she would hope. Told from both Vivian's and Johnny's perspectives, and inspired by true events, this novel explores how a dark chapter can irrevocably determine the shape of our lives.

Immune checkpoint inhibitors targeting PD-1 or CTLA-4 individually have shown substantial clinical benefits in the treatment of malignancies. We aimed to assess the safety and antitumour activity of cadonilimab monotherapy, a bispecific PD-1/CTLA-4 antibody, in patients with advanced solid tumours. This multicentre, open-label, phase 1b/2 trial was conducted across 30 hospitals in China. Patients aged 18 years or older with histologically or cytologically confirmed, unresectable advanced solid tumours, unsuccessful completion of at least one previous systemic therapy, and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible for inclusion. Patients who had previously received anti-PD-1, anti-PD-L1, or anti-CTLA-4 treatment were not eligible for inclusion. In the dose escalation phase of phase 1b, patients received intravenous cadonilimab at 6 mg/kg and 10 mg/kg every 2 weeks. In the dose expansion phase of phase 1b, cadonilimab at 6 mg/kg and a fixed dose of 450 mg were given intravenously every 2 weeks. In phase 2, cadonilimab at 6 mg/kg was administered intravenously every 2 weeks in three cohorts: patients with cervical cancer, oesophageal squamous cell carcinoma, and hepatocellular carcinoma. The primary endpoints were the safety of cadonilimab in phase 1b and objective response rate in phase 2, based on the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The safety analysis was done in all patients who received at least one dose of cadonilimab. Antitumour activity was assessed in the full analysis set for the cervical cancer cohort, and in all patients with measurable disease at baseline and who received at least one dose of cadonilimab in the oesophageal squamous cell carcinoma and hepatocellular carcinoma cohorts. The study is registered on ClinicalTrial.gov, NCT03852251, and closed to new participants; follow-up has been completed. Between Jan 18, 2019, and Jan 8, 2021, 240 patients (83 [43 male and 40 female] in phase 1b and 157 in phase 2) were enrolled. Phase 2 enrolled 111 female patients with cervical cancer, 22 patients with oesophageal squamous cell carcinoma (15 male and seven female), and 24 patients with hepatocellular carcinoma (17 male and seven female). During dose escalation, no dose-limiting toxicities occurred. Grade 3–4 treatment-related adverse events occurred in 67 (28%) of 240 patients; the most frequent grade 3 or worse treatment-related adverse events were anaemia (seven [3%]), increased lipase (four [2%]), decreased bodyweight (three [1%]), decreased appetite (four [2%]), decreased neutrophil count (three [1%]), and infusion-related reaction (two [1%]). 17 (7%) patients discontinued treatment due to treatment-related adverse events. 54 (23%) of 240 patients reported serious treatment-related adverse events, including five patients who died (one due to myocardial infarction; cause unknown for four). In phase 2, in the cervical cancer cohort, with a median follow-up of 14·6 months (IQR 13·1–17·5), the objective response rate was 32·3% (32 of 99; 95% CI 23·3–42·5). In the oesophageal squamous cell carcinoma cohort, with a median follow-up of 17·9 months (IQR 4·0–15·1), the objective response rate was 18·2% (four of 22; 95% CI 5·2–40·3). In the hepatocellular carcinoma cohort, with a median follow-up of 19·6 months (IQR 8·7–19·8), the objective response rate was 16·7% (four of 24; 95% CI 4·7–37·4). Cadonilimab showed an encouraging tumour response rate, with a manageable safety profile, suggesting the potential of cadonilimab for the treatment of advanced solid tumours. Akeso Biopharma. For the Chinese translation of the abstract see Supplementary Materials section.

My name is Sarah Lai. You won't have heard of me. A decade ago I was on the cusp of being a big deal. But that was a long time ago. Now, instead of working in Hollywood, I teach students about it. These are the two most important lessons you need to know about the film industry: those with the money have all the power and those with the power get whatever they want. Ignore these rules and the whole system will crumble. Stick to the rules and you'll succeed. But at what cost? Ask yourself, what would you have done?

Radiation-induced lung injury is a major dose-limiting toxicity in thoracic radiotherapy. Pirfenidone, an oral antifibrotic drug that is often used to treat idiopathic pulmonary fibrosis, could offer therapeutic benefits for patients with radiation-induced lung injury. We evaluated the efficacy and safety of pirfenidone in patients with grade 2 or grade 3 radiation-induced lung injury. This multicentre, open-label, randomised, phase 2 clinical trial enrolled patients with grade 2 or grade 3 radiation-induced lung injury diagnosed according to Common Terminology Criteria for Adverse Events version 5.0 from ten medical centres across China. Eligible patients were aged 18–75 years with an Eastern Cooperative Oncology Group performance status of 0–2 and had grade 2 or grade 3 radiation-induced lung injury. Patients were randomly assigned (1:1) using a computer-generated random number table to receive either pirfenidone plus glucocorticoids or glucocorticoids alone. Pirfenidone was given orally three times daily at doses of 200 mg in week 1, 300 mg in week 2, and 400 mg in weeks 3–24. Glucocorticoids were administered concurrently at the equivalent dose of prednisone 40 mg/day, divided into two oral doses, and maintained for 2 weeks, followed by a tapering schedule of 10 mg every 2 weeks over a period of 6 to 8 weeks. The control group received glucocorticoids only. The primary endpoint, evaluated in the modified intention-to-treat population, was the change in the percentage of carbon monoxide diffusing capacity (DLCO%) from baseline to week 24. Safety was assessed in all participants who received at least one dose of treatment. The trial is registered with ClinicalTrials.gov, NCT03902509, and has completed enrolment. Between Nov 29, 2021, and Dec 4, 2023, 134 patients were enrolled and randomly assigned, with 67 patients in each group study group. 105 (78%) of 134 patients were male and 29 (22%) were female. The median follow-up was 9·2 months (IQR 6·3–16·0). At week 24, the pirfenidone group showed an 8·0% improvement from baseline in DLCO%, whereas the control group showed a 2·4% reduction (least squares mean difference 10·4%, 95% CI 4·3–16·5; p=0·0010). The most common grade 3 or worse adverse events included pneumonia (four [6%] of 67 patients in the pirfenidone group vs eight [12%] of 67 patients in the control group), and rash (two [3%] of 67 patients in the pirfenidone group vs none in the control group). Serious adverse events occurred in 12 (18%) of 67 patients in the pirfenidone group and 11 (16%) of 67 patients in the control group. There were no treatment related deaths. Pirfenidone in combination with glucocorticoids provides a potential therapeutic strategy for grade 2 or grade 3 radiation-induced lung injury, addressing the unmet clinical need for effective antifibrotic therapy in patients receiving thoracic radiotherapy. Further investigation is needed to validate these findings in patients with worse radiation-induced lung injury than was studied here. Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Key R&D Program of China, National Natural Science Foundation of China, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center.

This monumental work provides a new perspective on the historical significance of famines in China over the past three hundred years. It examines the relationship between the interventionist state policies of the eighteenth-century Qing emperors ('The golden age of famine relief'), the environmental and political crises of the nineteenth and early twentieth centuries (when China was called 'the Land of Famine'), and the ambitions of the Mao era (which tragically led to the greatest famine in human history). In addition to a wide array of documentary sources, the book employs quantitative analysis to measure the economic impact of natural crises, state policies, and markets. In this way, the theories of Qing statesmen that have received much attention in recent scholarship are linked to actual practices and outcomes. Using the Zhili-Hebei region as its focus, the book also reveals the unusual role played by the institutions and policies designed to ensure food security for the capital, Beijing. -- Publisher description.

Plastic crystal neopentylglycol (NPG) exhibits colossal barocaloric effects (BCEs) with record-high entropy changes, offering exciting prospects for the field of solid-state cooling through the application of moderate pressures. Here, we show that the intermolecular hydrogen bond plays a key role in the orientational order of NPG molecules, while its broken due to thermal perturbation prominently weakens the activation barrier of orientational disorder. The analysis of hydrogen bond strength, rotational entropy free energy and entropy changes provides insightful understanding of BCEs in order-disorder transition. External pressure reduce the hydsrogen bond length and enhance the activation barrier of orientational disorder, which serves as a route of varying intermolecular interaction to tune the order-disorder transition. Our work provides atomic-scale insights on the orientational order-disorder transition of NPG as the prototypical plastic crystal with BCEs, which is helpful to achieve superior caloric materials by molecular designing in the near future. Colossal barocaloric effects with high entropy changes is reported in plastic crystal neopentylglycol, while microscopic mechanism needs to be further explored. Here, the authors show hydrogen bond related reorientational dynamics of neopentylglycol and provide insights in order-disorder transition.

Tea is the world's most popular non-alcoholic beverage. China and India are known to be the largest tea producing countries and recognized as the centers for the domestication of the tea plant (Camellia sinensis (L.) O. Kuntze). However, molecular studies on the origin, domestication and relationships of the main teas, China type, Assam type and Cambod type are lacking. Twenty-three nuclear microsatellite markers were used to investigate the genetic diversity, relatedness, and domestication history of cultivated tea in both China and India. Based on a total of 392 samples, high levels of genetic diversity were observed for all tea types in both countries. The cultivars clustered into three distinct genetic groups (i.e. China tea, Chinese Assam tea and Indian Assam tea) based on STRUCTURE, PCoA and UPGMA analyses with significant pairwise genetic differentiation, corresponding well with their geographical distribution. A high proportion (30%) of the studied tea samples were shown to possess genetic admixtures of different tea types suggesting a hybrid origin for these samples, including the Cambod type. We demonstrate that Chinese Assam tea is a distinct genetic lineage from Indian Assam tea, and that China tea sampled from India was likely introduced from China directly. Our results further indicate that China type tea, Chinese Assam type tea and Indian Assam type tea are likely the result of three independent domestication events from three separate regions across China and India. Our findings have important implications for the conservation of genetic stocks, as well as future breeding programs.

Literature supports a strong relationship between childhood maltreatment and mental illness but most studies reviewed are cross-sectional and/or use recall to assess maltreatment and are thus prone to temporality and recall bias. Research on the potential prospective impact of maltreatment reduction on the incidence of psychiatric disorders is scarce. Electronic databases and grey literature from 1990 to 2014 were searched for English-language cohort studies with criteria for depression and/or anxiety and non-recall measurement of childhood maltreatment. Systematic review with meta-analysis synthesized the results. Study quality, heterogeneity, and publication bias were examined. Initial screening of titles and abstracts resulted in 199 papers being reviewed. Eight high-quality articles met eligibility criteria. Population attributable fractions (PAFs) estimated potential preventive impact. The pooled odds ratio (OR) between any type of maltreatment and depression was 2.03 [95% confidence interval (CI) 1.37-3.01] and 2.70 (95% CI 2.10-3.47) for anxiety. For specific types of maltreatment and depression or anxiety disorders, the ORs were: physical abuse (OR 2.00, 95% CI 1.25-3.19), sexual abuse (OR 2.66, 95% CI 1.88-3.75), and neglect (OR 1.74, 95% CI 1.35-2.23). PAFs suggest that over one-half of global depression and anxiety cases are potentially attributable to self-reported childhood maltreatment. A 10-25% reduction in maltreatment could potentially prevent 31.4-80.3 million depression and anxiety cases worldwide. This review provides robust evidence of childhood maltreatment increasing the risk for depression and anxiety, and reinforces the need for effective programs and policies to reduce its occurrence.