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Scholars often assume that courts in authoritarian regimes cannot credibly protect foreign investors’ interests because these institutions lack judicial independence. In this article, we construct a novel data set on multinational corporations’ litigation activities in Chinese courts from 2002 to 2017. This supports the first systematic case-level analysis of foreign firms’ lawsuit outcomes in an authoritarian judiciary. We find that foreign companies frequently engage in litigation in authoritarian courts. Moreover, we theoretically and empirically distinguish between two types of government–business ties in terms of their effectiveness in incentivizing the host state to protect foreign investors’ interests. We argue that ad hoc, personal political connections deliver only trivial lawsuit success for multinational enterprises, while formal corporate partnerships with regime insiders can lead the state to structurally internalize foreign investors’ interests. In particular, we demonstrate that joint venture partnerships with state-owned enterprises help foreign firms obtain more substantial monetary compensation than other types of multinational enterprises. By contrast, the personal political connections of foreign firms’ board members do not foster meaningful judicial favoritism. These findings are robust to tests of alternative implications, matching procedures, and subsample robustness checks. This article advances our understanding of multinational corporations’ political risk in host countries, government–business relations, and authoritarian judicial institutions.

Existing literature on bias and third-party conflict management mainly focuses on the dichotomy of whether the mediator's bias as a whole can contribute to mediation onset and outcomes. I argue that we need more specific and disaggregated research on the mediator's bias because the side on which a prospective mediator's bias lies may significantly affect the likelihood of mediation onset. Why are some biased mediations initiated by third parties while others are not? By disentangling the mediator's bias and by distinguishing between different levels of bias, I find that the likelihood of mediation onset tends to increase if the potential mediator shares a closer political relationship with a conflicting state that has greater national capabilities or that is more authoritarian than the counterparty. However, the effect is largely conditional on the levels of the mediator's bias, where a more obvious level of bias is more likely to facilitate mediation initiation. This article advances our understanding of bias and international conflict mediation.

Why is trade with some countries more popular than with others? Linking the literature on regime type and trade cooperation with the literature on trade attitudes, the authors argue that the domestic political institutions and cooperative reputations of foreign states condition the willingness of the public and policy elites to deepen trade cooperation. Using survey experiments fielded on the American public and a unique sample of US foreign economic policymakers, the authors show that respondents prefer trade with democracies over trade with nondemocracies by large margins. Further, they find that this democratic advantage stems from a strong expectation that democracies will be more reliable and consistent cooperation partners. This study provides one of the first direct and causally identified tests of the mechanisms underlying theories of the political economy of regime type and international cooperation. Although the article focuses on the case of trade attitudes, the argument is general, suggesting that support for cooperation in other issue areas is conditional on similar factors.

A protocol based on chemical modulation of WNT activity is used to efficiently generate colonic organoids that recapitulate the molecular features of human colon tissue. Colonic organoids generated from induced pluripotent stem cells from patients with familial adenomatous polyposis provide an in vitro platform for disease modeling and preclinical drug testing. With the goal of modeling human disease of the large intestine, we sought to develop an effective protocol for deriving colonic organoids (COs) from differentiated human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs). Extensive gene and immunohistochemical profiling confirmed that the derived COs represent colon rather than small intestine, containing stem cells, transit-amplifying cells, and the expected spectrum of differentiated cells, including goblet and endocrine cells. We applied this strategy to iPSCs derived from patients with familial adenomatous polyposis (FAP-iPSCs) harboring germline mutations in the WNT-signaling-pathway-regulator gene encoding APC, and we generated COs that exhibit enhanced WNT activity and increased epithelial cell proliferation, which we used as a platform for drug testing. Two potential compounds, XAV939 and rapamycin, decreased proliferation in FAP-COs, but also affected cell proliferation in wild-type COs, which thus limits their therapeutic application. By contrast, we found that geneticin, a ribosome-binding antibiotic with translational 'read-through' activity, efficiently targeted abnormal WNT activity and restored normal proliferation specifically in APC-mutant FAP-COs. These studies provide an efficient strategy for deriving human COs, which can be used in disease modeling and drug discovery for colorectal disease.

BackgroundSurvival for glioblastoma remains very poor despite decades of research, with a 5-year survival of only 5%. The technological improvements that have revolutionized treatment of ischemic stroke and brain aneurysms have great potential in providing more precise and selective delivery of cancer therapeutic agents to brain tumors.MethodsWe describe for the first time the use of perfusion guidance to enhance the precision of endovascular super-selective intra-arterial (ESIA) infusions of mesenchymal stem cells loaded with Delta-24 (MSC-D24) in the treatment of glioblastoma (NCT 03896568).ResultsMRI imaging, which best defines the location of the tumor, is co-registered and fused with the patient’s position using cone beam CT, resulting in optimal vessel selection and confirmation of targeted delivery through volumetric perfusion imaging.ConclusionsThis technique of perfusion guided-ESIA injections (PG-ESIA) enhances our ability to perform targeted super-selective delivery of therapeutic agents for brain tumors.

Oral mucositis can be a debilitating and dangerous adverse effect of the chemoradiation used to prepare patients for bone marrow transplantation. Palifermin, a recombinant keratinocyte growth factor, was shown in this study to reduce the incidence and duration of severe oral mucositis after high-dose chemoradiation. Palifermin shows promise as a means of preventing oral mucositis, which can be a dangerous adverse effect of the chemoradiation. High-dose chemotherapy and radiotherapy followed by hematopoietic stem-cell support is a well-established treatment for hematologic cancers. Oral mucositis develops and requires treatment in approximately 70 to 80 percent of patients receiving radiation-based conditioning treatments. 1 , 2 The incidence and severity of oral mucositis vary with the conditioning regimen. Oral mucositis results from injury to epithelial cells that line the oral cavity. The damage causes changes ranging from mild atrophy to severe ulceration. Serious consequences include pain requiring opioid analgesia, potentially life-threatening infections, inadequate nutrition requiring parenteral feeding, and prolonged hospitalization. 1 – 5 Currently, no standard therapy prevents or treats severe oral mucositis. . . .

In this trial involving patients with atherosclerotic disease who were receiving effective statin therapy, those who were assigned to receive anacetrapib, a CETP inhibitor, had a lower risk of major coronary events than did those in the placebo group.

A highly effective HIV vaccine has been the goal of vaccinologists for nearly 35 years. A successful vaccine would need to induce broadly neutralizing antibodies (bnAbs) that are capable of neutralizing multiple HIV strains (see the Perspective by Agazio and Torres). Steichen et al. report a strategy in which the first vaccine shot can lead to immune responses that generate desired bnAbs. By combining knowledge of human antibody repertoires and structure to guide design, they validated candidate immunogens through functional preclinical testing. Saunders et al. designed immunogens with differences in binding strength for bnAb precursors, which enabled selection of rare mutations after immunization. The immunogens promoted bnAb precursor maturation in humanized mice and macaques. Science , this issue p. eaax4380 , p. eaay7199 ; see also p. 1197 Engineering antibodies against rare HIV mutations is required for HIV neutralizing antibody development.

Formerly incarcerated people have exceptionally poor health profiles and are at increased risk of preventable mortality when compared with their general population peers. However, not enough is known about the epidemiology of mortality in this population—specifically the rates, causes, and timing of death in specific subgroups and regions—to inform the development of targeted, evidence-based responses. We aimed to document the incidence, timing, causes, and risk factors for mortality after release from incarceration. We analysed linked administrative data from the multi-national Mortality After Release from Incarceration Consortium (MARIC) study. We examined mortality outcomes for 1 471 526 people released from incarceration in eight countries (Australia, Brazil, Canada, New Zealand, Norway, Scotland, Sweden, and the USA) from 1980 to 2018, across 10 534 441 person-years of follow-up (range 0–24 years per person). We combined data from 18 cohort studies using two-step individual participant data meta-analyses to estimate pooled all-cause and cause-specific crude mortality rates (CMRs) per 100 000 person-years, for specific time periods (first, daily from days 1–14; second, weekly from weeks 3–12; third, weeks 13–52 combined; fourth, weeks 53 and over combined; and fifth, total follow-up) after release, overall and stratified by age, sex, and region. 75 427 deaths were recorded. The all-cause CMR during the first week following release (1612 [95% CI 1048–2287]) was higher than during all other time periods (incidence rate ratio [IRR] compared with week 2: 1·5 [95% CI 1·2–1·8], I2=26·0%, weeks 3–4: 2·0 [1·5–2·6], I2=53·0%, and weeks 9–12: 2·2 [1·6–3·0], I2=70·5%). The highest cause-specific mortality rates during the first week were due to alcohol and other drug poisoning (CMR 657 [95% CI 332–1076]), suicide (135 [36–277]), and cardiovascular disease (71 [16–153]). We observed considerable variation in cause-specific CMRs over time since release and across regions. Pooled all-cause CMRs were similar between males (731 [95% CI 630–839]) and females (660 [560–767]) and were higher in older age groups. The markedly elevated rate of death in the first week post-release underscores an urgent need for investment in evidence-based, coordinated transitional healthcare, including treatment for mental illness and substance use disorders to prevent post-release deaths due to suicide and overdose. Temporal variations in rates and causes of death highlight the need for routine monitoring of post-release mortality. Australia's National Health and Medical Research Council.

Eliciting protective titers of HIV-1 broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development, but current vaccine strategies have yet to induce bnAbs in humans. Many bnAbs isolated from HIV-1-infected individuals are encoded by immunoglobulin gene rearrangments with infrequent naive B cell precursors and with unusual genetic features that may be subject to host regulatory control. Here, we administer antibodies targeting immune cell regulatory receptors CTLA-4, PD-1 or OX40 along with HIV envelope (Env) vaccines to rhesus macaques and bnAb immunoglobulin knock-in (KI) mice expressing diverse precursors of CD4 binding site HIV-1 bnAbs. CTLA-4 blockade augments HIV-1 Env antibody responses in macaques, and in a bnAb-precursor mouse model, CTLA-4 blocking or OX40 agonist antibodies increase germinal center B and T follicular helper cells and plasma neutralizing antibodies. Thus, modulation of CTLA-4 or OX40 immune checkpoints during vaccination can promote germinal center activity and enhance HIV-1 Env antibody responses. Elucidation of broadly neutralizing antibodies (bnAb) is a goal in HIV vaccine development. Here, Bradley et al. show that administration of CTLA-4 blocking antibody with vaccine antigens increases HIV-1 envelope antibody responses in macaques and a bnAb precursor mouse model.