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Truman and MacArthur offers an objective and comprehensive account of the very public confrontation between a sitting president and a well-known general over the military's role in the conduct of foreign policy. In November 1950, with the army of the Democratic Peoples Republic of Korea mostly destroyed, Chinese military forces crossed the Yalu River. They routed the combined United Nations forces and pushed them on a long retreat down the Korean peninsula. Hoping to strike a decisive blow that would collapse the Chinese communist regime in Beijing, General Douglas MacArthur, the commander of the Far East Theater, pressed the administration of President Harry S. Truman for authorization to launch an invasion of China across the Taiwan straits. Truman refused; MacArthur began to argue his case in the press, a challenge to the tradition of civilian control of the military. He moved his protest into the partisan political arena by supporting the Republican opposition to Truman in Congress. This violated the President's fundamental tenet that war and warriors should be kept separate from politicians and electioneering. On April 11, 1951 he finally removed MacArthur from command. Viewing these events through the eyes of the participants, this book explores partisan politics in Washington and addresses the issues of the political power of military officers in an administration too weak to carry national policy on its own accord. It also discusses America's relations with European allies and its position toward Formosa (Taiwan), the long-standing root of the dispute between Truman and MacArthur.

Includes The Bombing Of Japan During World War II illustrations pack with 120 maps, plans, and photosThe calculations for bringing large-scale hostilities to an end and for establishing a favorable environment in which post-combat operations, including the occupation of the enemy's homeland, can take place involve high-level military officers in the analysis of a wide range of considerations, many of which fall well beyond what would be traditionally recognized as strictly military in nature.In Unconditional Surrender Demobilization, and the Atomic Bomb, Dr. Michael Pearlman brings home this point through his shrewd assessment of the complex issues confronting U.S. officers as they debated the best course of action to follow in ending the war against Japan. Aside from the list of traditional concerns, such as the human cost of mounting an invasion of Japan, these officers had also to consider such intangibles as continued support for the war effort on the American home front.Thanks to Pearlman's research, the reader comes away with a deeper understanding of why these officers made the recommendations they did to the president and why the president decided to drop the atomic bomb to end World War II.

Background Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax ® -L) to standard therapy for newly diagnosed glioblastoma. Methods After surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS). Results For the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months from surgery. Because of the cross-over trial design, nearly 90% of the ITT population received DCVax-L. For patients with methylated MGMT (n = 131), mOS was 34.7 months from surgery, with a 3-year survival of 46.4%. As of this analysis, 223 patients are ≥ 30 months past their surgery date; 67 of these (30.0%) have lived ≥ 30 months and have a Kaplan-Meier (KM)-derived mOS of 46.5 months. 182 patients are ≥ 36 months past surgery; 44 of these (24.2%) have lived ≥ 36 months and have a KM-derived mOS of 88.2 months. A population of extended survivors (n = 100) with mOS of 40.5 months, not explained by known prognostic factors, will be analyzed further. Only 2.1% of ITT patients (n = 7) had a grade 3 or 4 adverse event that was deemed at least possibly related to the vaccine. Overall adverse events with DCVax were comparable to standard therapy alone. Conclusions Addition of DCVax-L to standard therapy is feasible and safe in glioblastoma patients, and may extend survival. Trial registration Funded by Northwest Biotherapeutics; Clinicaltrials.gov number: NCT00045968; https://clinicaltrials.gov/ct2/show/NCT00045968?term=NCT00045968&rank=1 ; initially registered 19 September 2002

Over a dozen millisecond pulsars are ablating low-mass companions in close binary systems. In the original ‘black widow’, the eight-hour orbital period eclipsing pulsar PSR J1959+2048 (PSR B1957+20) 1 , high-energy emission originating from the pulsar 2 is irradiating and may eventually destroy 3 a low-mass companion. These systems are not only physical laboratories that reveal the interesting results of exposing a close companion star to the relativistic energy output of a pulsar, but are also believed to harbour some of the most massive neutron stars 4 , allowing for robust tests of the neutron star equation of state. Here we report observations of ZTF J1406+1222, a wide hierarchical triple hosting a 62-minute orbital period black widow candidate, the optical flux of which varies by a factor of more than ten. ZTF J1406+1222 pushes the boundaries of evolutionary models 5 , falling below the 80-minute minimum orbital period of hydrogen-rich systems. The wide tertiary companion is a rare low-metallicity cool subdwarf star, and the system has a Galactic halo orbit consistent with passing near the Galactic Centre, making it a probe of formation channels, neutron star kick physics 6 and binary evolution. ZTF J1406+1222 is a wide hierarchical triple system that hosts a low-metallicity subdwarf star and a ‘black widow’ millisecond pulsar that has a highly varying optical flux and a 62-minute period.

Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and aggressive cancer predisposition syndrome. Because a scarcity of data on this condition contributes to management challenges and poor outcomes, we aimed to describe the clinical spectrum, cancer biology, and impact of genetics on patient survival in CMMRD. In this cohort study, we collected cross-sectional and longitudinal data on all patients with CMMRD, with no age limits, registered with the International Replication Repair Deficiency Consortium (IRRDC) across more than 50 countries. Clinical data were extracted from the IRRDC database, medical records, and physician-completed case record forms. The primary objective was to describe the clinical features, cancer spectrum, and biology of the condition. Secondary objectives included estimations of cancer incidence and of the impact of the specific mismatch-repair gene and genotype on cancer onset and survival, including after cancer surveillance and immunotherapy interventions. We analysed data from 201 patients (103 males, 98 females) enrolled between June 5, 2007 and Sept 9, 2022. Median age at diagnosis of CMMRD or a related cancer was 8·9 years (IQR 5·9–12·6), and median follow-up from diagnosis was 7·2 years (3·6–14·8). Endogamy among minorities and closed communities contributed to high homozygosity within countries with low consanguinity. Frequent dermatological manifestations (117 [93%] of 126 patients with complete data) led to a clinical overlap with neurofibromatosis type 1 (35 [28%] of 126). 339 cancers were reported in 194 (97%) of 201 patients. The cumulative cancer incidence by age 18 years was 90% (95% CI 80–99). Median time between cancer diagnoses for patients with more than one cancer was 1·9 years (IQR 0·8–3·9). Neoplasms developed in 15 organs and included early-onset adult cancers. CNS tumours were the most frequent (173 [51%] cancers), followed by gastrointestinal (75 [22%]), haematological (61 [18%]), and other cancer types (30 [9%]). Patients with CNS tumours had the poorest overall survival rates (39% [95% CI 30–52] at 10 years from diagnosis; log-rank p<0·0001 across four cancer types), followed by those with haematological cancers (67% [55–82]), gastrointestinal cancers (89% [81–97]), and other solid tumours (96% [88–100]). All cancers showed high mutation and microsatellite indel burdens, and pathognomonic mutational signatures. MLH1 or MSH2 variants caused earlier cancer onset than PMS2 or MSH6 variants, and inferior survival (overall survival at age 15 years 63% [95% CI 55–73] for PMS2, 49% [35–68] for MSH6, 19% [6–66] for MLH1, and 0% for MSH2; p<0·0001). Frameshift or truncating variants within the same gene caused earlier cancers and inferior outcomes compared with missense variants (p<0·0001). The greater deleterious effects of MLH1 and MSH2 variants as compared with PMS2 and MSH6 variants persisted despite overall improvements in survival after surveillance or immune checkpoint inhibitor interventions. The very high cancer burden and unique genomic landscape of CMMRD highlight the benefit of comprehensive assays in timely diagnosis and precision approaches toward surveillance and immunotherapy. These data will guide the clinical management of children and patients who survive into adulthood with CMMRD. The Canadian Institutes for Health Research, Stand Up to Cancer, Children's Oncology Group National Cancer Institute Community Oncology Research Program, Canadian Cancer Society, Brain Canada, The V Foundation for Cancer Research, BioCanRx, Harry and Agnieszka Hall, Meagan's Walk, BRAINchild Canada, The LivWise Foundation, St Baldrick Foundation, Hold'em for Life, and Garron Family Cancer Center.

ObjectiveAn understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined.DesignTo identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling.ResultsWe identified 13 loci that reached genome-wide significance (p<5×10−8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer.ConclusionGenetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.

Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups ( p -values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice. Most genetic studies have been done on European cohorts, which affects the efficacy of polygenic risk scores in non-European populations. Here, the authors demonstrate that a colorectal cancer PRS including Asian and European ancestries has improved performance over the European-centric PRS across racial and ethnic groups.

Following publication of the original article [1], the authors reported an error in the spelling of one of the author names. In this Correction the incorrect and correct author names are indicated and the author name has been updated in the original publication. The authors also reported an error in the Methods section of the original article. In this Correction the incorrect and correct versions of the affected sentence are indicated. The original article has not been updated with regards to the error in the Methods section.

ABSTRACT Background: The dry powder inhaler (DPI) device for budesonide inhalation powder 200 μg (DPI‑A*) was redesigned to improve dosing consistency and provide new features (budesonide inhalation powder 90 μg and 180 μg; DPI‑B†). Objective: Two multicenter, parallel-group, double-blind, randomized, 12-week studies compared the efficacy and safety of budesonide delivered via each DPI versus placebo, and the systemic exposure of budesonide from each device. Methods: Asthmatic adults with mild-to-moderate asthma (N = 621) and patients 6-17 years with mild asthma (N = 516) received budesonide DPI‑B 360 μg or DPI‑A 400 μg twice-daily (total daily dose 720 μg or 800 μg), budesonide DPI‑B 180 μg or DPI‑A 200 μg once daily (total daily dose 180 μg or 200 μg), or matching placebo. Change in forced expiratory volume in 1 second (FEV1) and secondary variables (asthma symptoms, β2-adrenergic agonist use, peak expiratory flow [PEF], and withdrawals due to worsening asthma) versus placebo were measured. Results: In both studies, FEV1 significantly ( p < 0.05) improved for all active treatments versus placebo except once-daily budesonide DPI‑B 180 μg in adults. In the adult study, significantly ( p < 0.05) greater improvements in all secondary variables occurred with all active treatments versus placebo. In the pediatric/adolescent study, improvements in AM/PM PEF were significantly (p ≤ 0.011) greater with twice-daily budesonide DPI‑B 360 μg versus placebo. Numerically fewer patients in all active-treatment groups withdrew due to worsening asthma versus placebo. Adverse event profiles were similar among groups. In the pediatric/adolescent study, no significant differences in mean 24-h urine cortisol or cortisol : creatinine ratio assessments were observed between the active treatment groups and the placebo group. Although pharmacokinetic variables were generally similar across subgroups in the adult (n = 77) and pediatric/adolescent (n = 32) studies, pairwise treatment comparisons of twice-daily budesonide DPI‑B 360 μg versus DPI‑A 400 μg and once-daily budesonide DPI‑B 180 μg versus DPI‑A 200 μg showed large variability for the area under the drug plasma concentration-time curve over the dosing interval and the maximum detected drug plasma concentration. Conclusions: The efficacy and safety of budesonide DPI‑A and DPI‑B versus placebo were demonstrated across the low to medium inhaled corticosteroid dose range in children ≥ 6 years with very mild asthma and adolescents and adults with mild-to-moderate asthma. The study is limited by the evaluation of only two doses for each product in both studies. Additionally, the studies were not designed to test equivalence or noninferiority between the active products. Pharmacokinetic characterization was limited because of the small sample sizes.