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"Chui, Michael"
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Financial Systems in Europe, the USA, and ASIA
Financial structure is an important determinant of the efficiency and stability of financial systems and the channels through which monetary policy is transmitted. We document the substantial differences in the financial systems of the euro area, the UK, the USA, Japan, and non-Japan Asia. The traditional classification of bank-based and market-based systems is shown to be too simplistic. We focus on two particular aspects of financial structure: financial institutions and the housing and mortgage markets. It is shown that institutional investors differ in important ways across the regions considered. One recent change is that Central Banks, particularly those in Asia, have become significant institutional investors. Housing and mortgage markets differ even more. We are still a long way from understanding which kind of financial structure is best.
Journal Article
Advancements in Low-Grade Serous Carcinoma of the Ovary and Peritoneum
Purpose of ReviewLow-grade serous ovarian cancer (LGSOC) is a rare form of epithelial ovarian cancer that generally exhibits a protracted course and is less sensitive to chemotherapy than high-grade serous ovarian cancer. Over the past decade, it has become clear that patients with LGSOC have a clinically distinct course and are molecularly and histologically unique from patients with high-grade serous ovarian cancer.Recent FindingsEndocrine therapy is frequently used for the treatment of patients with recurrent LGSOC and is now also part of the standard upfront treatment of this disease, with an ongoing phase III clinical trial seeking to determine if chemotherapy can be eliminated altogether from the initial treatment of LGSOC. Tumors are frequently found to exhibit alterations affecting the mitogen-activated protein kinase (MAPK) pathway, recently leading to developments in the use of targeted treatments for those patients with recurrent disease.SummaryLGSOC is a clinically, histologically, and molecularly unique form of epithelial ovarian cancer. Recent advances in the understanding of endocrine and molecular drivers of this disease have led to changes in both the treatment of newly diagnosed and recurrent disease, with ongoing studies focused on refining upfront therapy and seeking novel targeted combinations for those patients with recurrent disease.
Journal Article
In‐depth molecular profiling of the biphasic components of uterine carcinosarcomas
Uterine carcinosarcoma is a clinically aggressive malignancy composed of a mix of carcinomatous and sarcomatous elements. We performed targeted next‐generation sequencing of 27 uterine cancer and sarcoma genes together with immunohistochemical analyses of selected proteins in 30 uterine carcinosarcomas. This included 13 cases in which the distinct carcinoma and sarcoma components were sequenced separately and 10 cases where the metastatic tumours were analysed in addition to the primary tumours. We identified non‐synonymous somatic mutations in 90% of the cases, with 27 of 30 cases (90%) harbouring TP53 alterations. The PI3K pathway was the most commonly mutated signalling pathway with mutations identified in PIK3CA, PTEN, PIK3R1, and/or PIK3R2 in two‐thirds of the cases. Mutations in FBXW7, PPP2R1A, ARID1A and KRAS were demonstrated in a minority of cases. In cases where the carcinomatous and sarcomatous components were separately analysed, most of the mutations identified were present in both components, indicating a common origin for the two components. Furthermore, the same TP53 alterations and/or PI3K pathway mutations seen in the primary tumours were also identified in the metastatic sites. Overall, carcinosarcomas exhibited heterogeneous molecular features that resemble the heterogeneity seen in endometrial carcinomas, with some showing endometrioid carcinoma‐like and others showing serous carcinoma‐like mutation profiles. While patients with serous‐like tumours presented more frequently with advanced‐stage disease compared to patients with endometrioid‐like tumours, there was no statistical difference in outcome between the two groups. Our results provide insights into the oncogenesis of uterine carcinosarcoma and identify targetable mutations that represent early oncogenic events. The findings of the different molecular types of uterine carcinosarcoma that parallel the different molecular types in endometrial carcinoma may have future treatment implications with targeted therapies.
Journal Article
Case Report: Adrenal LH/hCG Receptor Overexpression and Gene Amplification Causing Pregnancy-Induced Cushing's Syndrome
Transient pregnancy-induced Cushing's syndrome (CS) is extremely rare, with only several cases reported in the literature. Ectopic LH/hCG-receptors (LHCGR) in the adrenal gland have been suggested to be involved in the pathogenesis of this condition. We report the clinical, molecular, and genetic features of a patient with pregnancy-induced CS. A 29-year-old female patient developed CS during multiple pregnancies, leading to repeated miscarriage. Signs and symptoms of hypercortisolism resolved soon after delivery or abortion, only to recur in subsequent pregnancies. In the non-pregnant state, hCG stimulation testing resulted in elevated cortisol levels. Serum cortisol was not suppressible with dexamethasone. The adrenals exhibited bilateral adrenal cortical nodular hyperplasia. Quantitative RT-PCR revealed a 2-fold increase in LHCGR and progesterone receptor mRNA expression and decreased estrogen receptor-beta expression in the patient's adrenal tissue relative to normal adrenals. Higher intensity of immunostaining for LHCGR was observed, particularly within the nodular lesions, compared to controls. Quantitative PCR revealed a LHCGR-to-β-actin ratio of 1.5 in genomic DNA from adrenal and peripheral leukocytes, suggesting the presence of a germline duplication of the LHCGR gene. LHCGR overexpression resulting from germline gene duplication may be a potential pathogenic mechanism underlying this case of pregnancy-induced CS.
Journal Article
Histopathologic Features of Prognostic Significance in High-Grade Osteosarcoma
Context .- In osteosarcoma treated with neoadjuvant chemotherapy the extent of tumor necrosis on resection is considered an indicator of treatment response, and this has been shown to correlate with survival in most but not all studies. Objective .- To identify additional histologic variables of prognostic significance in high-grade osteosarcoma. Design .- Slides of pretreatment biopsy and primary postneoadjuvant chemotherapy resections from 165 patients with high-grade osteosarcoma were reviewed. Univariate (Kaplan-Meier) and multivariate (Cox regression) analyses were performed to identify clinical and histomorphologic attributes associated with overall survival. Results .- Univariate analyses confirmed the prognostic significance of metastatic status on presentation, primary tumor size, anatomic site, and histologic subtype. Additionally, the identification of lymphovascular invasion, 10% or more residual viable tumor, and 10 or more mitoses per 10 high-powered fields assessed in posttreatment resections were associated with poor survival, retaining significance in multivariate analyses. Based on results from multivariate analysis, we developed a prognostic index incorporating primary tumor size and site, and significant histologic features assessed on resection (ie, lymphovascular invasion status, mitotic rate, and extent of viable tumor). This scoring system segregates patients into 3 risk categories with significant differences in overall survival and retained significance in an independent validation set of 42 cases. Conclusions .- The integration of clinical and microscopic features improves prognostication of patients with osteosarcoma.
Journal Article
Follicular epithelial dysplasia of the thyroid: morphological and immunohistochemical characterization of a putative preneoplastic lesion to papillary thyroid carcinoma in chronic lymphocytic thyroiditis
In chronic lymphocytic thyroiditis (CLT), the follicular epithelial cells display cytological atypia resembling papillary thyroid carcinoma (PTC), and epidemiological studies have suggested an increased risk of PTC in patients with this condition. While reactive atypia is observed diffusely in CLT-affected thyroid parenchyma, it is not unusual to find microscopic foci morphologically distinct from the surrounding parenchyma, exhibiting more pronounced cytological and architectural atypia. These small atypical lesions, which we term “follicular epithelial dysplasia” (FED), are particularly prominent in cases of severe CLT, yet lack invasive growth, papillary architecture, or intranuclear pseudoinclusions. To gain further insight into their biological significance, we constructed a tissue microarray of 70 cases of CLT, comprised of morphologically normal thyroid, thyroid with reactive atypia, FED, follicular nodular disease (nodular hyperplasia or follicular adenoma), and PTC. Immunohistochemical staining was performed for a marker panel including PTC (HBME-1, cytokeratin 19, galectin-3, and cyclin-D1) as well as TTF-1, thyroglobulin, and p63. Slides were digitally scanned and immunohistochemical staining evaluated using automated image analysis software. FED lesions were positive for TTF-1 and thyroglobulin (50/50, 100 %), though some (13/50, 26 %) also expressed p63. Similar to PTC, strong diffuse staining was observed for HBME-1 (43/50, 86 %), cytokeratin 19 (48/50, 96 %), galectin-3 (20/50, 40 %) and cyclin-D1 (38/50, 76 %). In contrast, normal thyroid, reactive atypia, and follicular nodular disease were negative, or at most, exhibited focal weak staining for HBME-1, cytokeratin 19, and galectin-3. The results of this study demonstrate the presence of atypical microscopic lesions in CLT with an immunohistochemical profile similar to PTC, supporting the concept of a premalignant lesion preceding PTC, arising in the context of severe chronic inflammation.
Journal Article
Delivering services to the public—digitally—with Jennifer Pahlka
A former US deputy chief technology officer talks about how digitization can be used to create a government that works for the people.Jennifer Pahlkais the founder of Code for America, served as the United States government’s deputy chief technology officer, and is author of the book Recoding America: Why Government Is Failing in the Digital Age and How We Can Do Better. Michael Chui (co-host):Janet, on this podcast we have had a lot of guests who have shared their insights about the economy, including how monetary and fiscal policy can influence labor markets, capital markets, and what that means for ordinary people. Or, as one of our previous guests, Tyler Cowen, has described it: “building state capacity.” [...]they had a policy change around how kids were assigned to public schools, or what schools the parents could apply for their kids to go to. [...]all this other stuff, number one, in enterprises in the private sector, but then particularly for the public sector, you get these things, and our expectations are a lot lower. If you know it’s that simple to deliver a service on your phone in the private sector, then you ask the question, why is it so hard in government?
Report
Money, technology and banking: what lessons can China teach the rest of the world?
Technology companies entering the financial services industry have become a global phenomenon over the past decade. This trend is most remarkable in China where two large technology firms (BigTechs) have emerged as important market players, especially in payment services. This paper examines the factors driving this development and whether the Chinese experience could be applied elsewhere. Several lessons emerge: first, like any company in a network industry, it is important to build and maintain a large user base and that is the key factor behind BigTechs' expansion into the financial industry. On this basis, these BigTechs can be seen as \"accidental financiers\" rather than \"aggressive invaders\". Second, these firms are cautious in offering higher-risk financial services as investment losses could lead to an exodus of customers. Third, Chinese authorities' regulatory tolerance during the early stage has been a key supporting factor and helped fostering innovation benefits. But that was balanced by the implementation of capital and liquidity rules to keep BigTechs from \"excessive\" growth, mis-selling of financial products and posing systemic risks. Fourth, initial conditions and government support matter. The rapid growth has benefitted from China's large population, the availability of low-cost mobile handsets and heavy investment by the government on mobile communication infrastructure. These may not be easily be replicated elsewhere. Last, BigTechs' overseas expansion may require policy coordination between home and host authorities to keep track of emerging risks.
Paper