New York University Florence

Chromosome imbalance (aneuploidy) is the major cause of pregnancy loss and congenital disorders in humans. Analyses of small biopsies from human embryos suggest that aneuploidy commonly originates during early divisions, resulting in mosaicism. However, the developmental potential of mosaic embryos remains unclear. We followed the distribution of aneuploid chromosomes across 73 unselected preimplantation embryos and 365 biopsies, sampled from four multifocal trophectoderm (TE) samples and the inner cell mass (ICM). When mosaicism impacted fewer than 50% of cells in one TE biopsy (low-medium mosaicism), only 1% of aneuploidies affected other portions of the embryo. A double-blinded prospective non-selection trial (NCT03673592) showed equivalent live-birth rates and miscarriage rates across 484 euploid, 282 low-grade mosaic, and 131 medium-grade mosaic embryos. No instances of mosaicism or uniparental disomy were detected in the ensuing pregnancies or newborns, and obstetrical and neonatal outcomes were similar between the study groups. Thus, low-medium mosaicism in the trophectoderm mostly arises after TE and ICM differentiation, and such embryos have equivalent developmental potential as fully euploid ones.

OBJECTIVE: To characterize clinical and clinicopathologic findings, response to treatment, and causes of systemic hypertension in cats with hypertensive retinopathy. DESIGN: Retrospective study. ANIMALS: 69 cats with hypertensive retinopathy. PROCEDURE: Medical records from cats with systemic hypertension and hypertensive retinopathy were reviewed. RESULTS: Most cats (68.1%) were referred because of vision loss; retinal detachment, hemorrhage, edema, and degeneration were common findings. Cardiac abnormalities were detected in 37 cats, and neurologic signs were detected in 20 cats. Hypertension was diagnosed concurrently with chronic renal failure (n = 22), hyperthyroidism (5), diabetes mellitus (2), and hyperaldosteronism (1). A clearly identifiable cause for hypertension was not detected in 38 cats; 26 of these cats had mild azotemia, and 12 did not have renal abnormalities. Amlodipine decreased blood pressure in 31 of 32 cats and improved ocular signs in 18 of 26 cats. CONCLUSIONS AND CLINICAL RELEVANCE: Retinal lesions, caused predominantly by choroidal injury, are common in cats with hypertension. Primary hypertension in cats may be more common than currently recognized. Hypertension should be considered in older cats with acute onset of blindness; retinal edema, hemorrhage, or detachment; cardiac disease; or neurologic abnormalities. Cats with hypertension-induced ocular disease should be evaluated for renal failure, hyperthyroidism, diabetes mellitus, and cardiac abnormalities. Blood pressure measurements and funduscopic evaluations should be performed routinely in cats at risk for hypertension (preexisting renal disease, hyperthyroidism, and age > 10 years). Amlodipine is an effective antihypertensive agent in cats.

Potentially carcinogenic compounds may cause cancer through direct DNA damage or through indirect cellular or physiological effects. To study possible carcinogens, the fields of endocrinology, genetics, epigenetics, medicine, environmental health, toxicology, pharmacology and oncology must be considered. Disruptive chemicals may also contribute to multiple stages of tumor development through effects on the tumor microenvironment. In turn, the tumor microenvironment consists of a complex interaction among blood vessels that feed the tumor, the extracellular matrix that provides structural and biochemical support, signaling molecules that send messages and soluble factors such as cytokines. The tumor microenvironment also consists of many host cellular effectors including multipotent stromal cells/mesenchymal stem cells, fibroblasts, endothelial cell precursors, antigen-presenting cells, lymphocytes and innate immune cells. Carcinogens can influence the tumor microenvironment through effects on epithelial cells, the most common origin of cancer, as well as on stromal cells, extracellular matrix components and immune cells. Here, we review how environmental exposures can perturb the tumor microenvironment. We suggest a role for disrupting chemicals such as nickel chloride, Bisphenol A, butyltins, methylmercury and paraquat as well as more traditional carcinogens, such as radiation, and pharmaceuticals, such as diabetes medications, in the disruption of the tumor microenvironment. Further studies interrogating the role of chemicals and their mixtures in dose-dependent effects on the tumor microenvironment could have important general mechanistic implications for the etiology and prevention of tumorigenesis.

BACKGROUND: Early detection and treatment of melanoma is important for optimal clinical outcome, leading to biopsy of pigmented lesions deemed suspicious for the disease. The vast majority of such lesions are benign. Thus, a more objective and accurate means for detection of melanoma is needed to identify lesions for excision. OBJECTIVES: To provide proof-of-principle that epidermal genetic information retrieval (EGIR™; DermTech International, La Jolla, CA, U.S.A.), a method that noninvasively samples cells from stratum corneum by means of adhesive tape stripping, can be used to discern melanomas from naevi. METHODS: Skin overlying pigmented lesions clinically suspicious for melanoma was harvested using EGIR. RNA isolated from the tapes was amplified and gene expression profiled. All lesions were removed for histopathological evaluation. RESULTS: Supervised analysis of the microarray data identified 312 genes differentially expressed between melanomas, naevi and normal skin specimens (P<0·001, false discovery rate q<0·05). Surprisingly, many of these genes are known to have a role in melanocyte development and physiology, melanoma, cancer, and cell growth control. Subsequent class prediction modelling of a training dataset, consisting of 37 melanomas and 37 naevi, discovered a 17-gene classifier that discriminates these skin lesions. Upon testing with an independent dataset, this classifier discerned in situ and invasive melanomas from naevi with 100% sensitivity and 88% specificity, with an area under the curve for the receiver operating characteristic of 0·955. CONCLUSIONS: These results demonstrate that EGIR-harvested specimens can be used to detect melanoma accurately by means of a 17-gene genomic biomarker.

BACKGROUND: : The treatment of binge eating disorder (BED) is still the object of debate. In the present study, the effectiveness of antidepressant drugs (fluoxetine - FLX - 60 mg/day, fluvoxamine - FLV -300 mg/day), cognitive-behavioural therapy (CBT) and combined treatments (CBT + FLX, CBT + FLV) has been evaluated in a randomized, clinical trial. Results at the end of the active treatment (in the 24th week) and 1-year follow-up outcomes have been evaluated. METHODS: One hundred eight (44 M, 64 F) BED patients were randomly assigned to either CBT, FLX (60 mg/day), FLV (300 mg/day), CBT + FLX or CBT + FLV, for 24 weeks. At the beginning (T0), at the end (T1) of treatment and after 1 year (T2), body mass index (BMI) and eating attitude and behaviours (by EDE 12.0D) were assessed. RESULTS: At T1, BMI and EDE scores were significantly reduced in CBT, CBT + FLX and CBT + FLV, but not in the FLX and FLV treatment groups. In the CBT + FLV group, a greater (p < 0.05) reduction of EDE total scores was observed, when compared to CBT + FLX or CBT treatment groups. At T2, BMI was significantly higher than at T1, but still significantly lower than at T0 in the CBT, CBT + FLX and CBT + FLV groups, while EDE scores remained unchanged from T1 in all treatment groups. CONCLUSIONS: CBT was more effective than FLX or FLV in the treatment of BED. The addition of FLX to CBT does not seem to provide any clear advantage, while the addition of FLV could enhance the effects of CBT on eating behaviours. Modifications of eating behaviours are maintained at the 1-year follow-up, although the lost weight was partly regained.

Abstract Human rights in general and the international human rights system in particular have come under increasing attack in recent years. Quite apart from the domestic and global political events since 2016, including an apparent retreat from international institutions, the human rights system has in recent times come in for severe criticism from academic scholars. Amongst the various criticisms levelled have been: (1) the ineffectiveness and lack of impact of international human rights regimes, (2) the ambiguity and lack of specificity of human rights standards, (3) the weakness of international human rights enforcement mechanisms, and (4) the claim to universalism of human rights standards coupled with the hegemonic imposition of these standards on diverse parts of the world. This article responds to several of those criticisms by introducing the idea of experimentalist governance, interpreting key aspects of the functioning of certain international human rights treaties from the perspective of experimentalist governance theory, and surveying a body of recent scholarship on the effectiveness of such treaties. Contrary to the depiction of international human rights regimes as both ineffective and top-down, the article argues that they function at their best as dynamic, participatory, and iterative systems. Experimentalist governance offers a theory of the causal effectiveness of human rights treaties, brings to light a set of features and interactions that are routinely overlooked in many accounts, and suggests possible avenues for reform of other human rights treaty regimes with a view to making them more effective in practice.

The number of Web site visits, Facebook friends, or Twitter followers that politicians attract varies greatly, but little is known about what drives politicians' online popularity. In this article, we use data from a systematic tracking of congressional candidates' popularity on four Web platforms in the 112 most competitive congressional districts in the 2010 U.S. midterm elections to address that question. Using multivariate regression models, we show that while district-level socioeconomic characteristics have little effect on candidates' online popularity, challengers and candidates in open-seat races tend to attract larger audiences online, as do candidates who are more visible on political blogs. Surprisingly, how intensely candidates are covered in news media, how popular they are in opinion polls, and how much money they spend during the campaign show no significant effect. These findings help us understand the dynamics of Internet politics, and they have wider implications for candidate competition and party politics.

Abstract We present a systematic calculation of the corrections of the stress-energy tensor and currents of the free boson and Dirac fields up to second order in thermal vorticity, which is relevant for relativistic hydrodynamics. These corrections are non-dissipative because they survive at general thermodynamic equilibrium with non vanishing mean values of the conserved generators of the Lorentz group, i.e. angular momenta and boosts. Their equilibrium nature makes it possible to express the relevant coefficients by means of correlators of the angular-momentum and boost operators with stress-energy tensor and current, thus making simpler to determine their so-called “Kubo formulae”. We show that, at least for free fields, the corrections are of quantum origin and we study several limiting cases and compare our results with previous calculations. We find that the axial current of the free Dirac field receives corrections proportional to the vorticity independently of the anomalous term.

Pathology informatics has evolved to varying levels around the world. The history of pathology informatics in different countries is a tale with many dimensions. At first glance, it is the familiar story of individuals solving problems that arise in their clinical practice to enhance efficiency, better manage (e.g., digitize) laboratory information, as well as exploit emerging information technologies. Under the surface, however, lie powerful resource, regulatory, and societal forces that helped shape our discipline into what it is today. In this monograph, for the first time in the history of our discipline, we collectively perform a global review of the field of pathology informatics. In doing so, we illustrate how general far-reaching trends such as the advent of computers, the Internet and digital imaging have affected pathology informatics in the world at large. Major drivers in the field included the need for pathologists to comply with national standards for health information technology and telepathology applications to meet the scarcity of pathology services and trained people in certain countries. Following trials by a multitude of investigators, not all of them successful, it is apparent that innovation alone did not assure the success of many informatics tools and solutions. Common, ongoing barriers to the widespread adoption of informatics devices include poor information technology infrastructure in undeveloped areas, the cost of technology, and regulatory issues. This review offers a deeper understanding of how pathology informatics historically developed and provides insights into what the promising future might hold.

BACKGROUND: Customized employment (CE) is a strategy that has shown promise in improving poor employment outcome for individuals with disabilities. The term customized employment was first used in 2001 and originated from efforts by the Department o

Raman spectroscopy has the potential to differentiate among the various stages leading to high-grade cervical cancer such as normal, squamous metaplasia, and low-grade cancer. For Raman spectroscopy to successfully differentiate among the stages, an applicable statistical method must be developed. Algorithms like linear discriminant analysis (LDA) are incapable of differentiating among three or more types of tissues. We developed a novel statistical method combining the method of maximum representation and discrimination feature (MRDF) to extract diagnostic information with sparse multinomial logistic regression (SMLR) to classify spectra based on nonlinear features for multiclass analysis of Raman spectra. We found that high-grade spectra classified correctly 95% of the time; low-grade data classified correctly 74% of the time, improving sensitivity from 92 to 98% and specificity from 81 to 96% suggesting that MRDF with SMLR is a more appropriate technique for categorizing Raman spectra. SMLR also outputs a posterior probability to evaluate the algorithm's accuracy. This combined method holds promise to diagnose subtle changes leading to cervical cancer.

OBJECTIVE: Computed tomography (CT)-compatible robots, both commercial and research-based, have been developed with the intention of increasing the accuracy of needle placement and potentially improving the outcomes of therapies in addition to reducing clinical staff and patient exposure to radiation during CT fluoroscopy. In the case of highly inaccessible lesions that require multiple plane angulations, robotically assisted needles may improve biopsy access and targeted drug delivery therapy by avoidance of the straight line path of normal linear needles. METHODS: We report our preliminary experience of performing radiofrequency ablation of the liver using a robotic-assisted CT guidance system on 11 patients (17 lesions). RESULTS/CONCLUSION: Robotic-assisted planning and needle placement appears to have high accuracy, is technically easier than the non-robotic-assisted procedure, and involves a significantly lower radiation dose to both patient and support staff. KEY POINTS: • An early experience of robotic-assisted radiofrequency ablation is reported • Robotic-assisted RFA improves accuracy of hepatic lesion targeting • Robotic-assisted RFA makes the procedure technically easier with significant lower radiation dose.

This article provides a retrospective of twenty years of employment for persons with significant disabilities detailing trends, short-comings and promising practices. The article coincides with the 20th anniversary of the Journal of Vocational Rehabilitation.

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by the presence in the patient's hematopoietic system of a large cell population with a mutation in the X-linked PIG-A gene. Although this abnormal cell population is often found to be monoclonal, it is not unusual that 2 or even several PIG-A mutant clones coexist in the same patient. Therefore, it has been suggested that the PIG-A gene may be hypermutable in PNH. By a method we have recently developed for measuring the intrinsic rate of somatic mutations (mu) in humans, in which PIG-A itself is used as a sentinel gene, we have found that in 5 patients with PNH, mu ranged from 1.24 x 10(-7) to 11.2 x 10(-7), against a normal range of 2.4 x 10(-7) to 29.6 x 10(-7) mutations per cell division. We conclude that genetic instability of the PIG-A gene is not a factor in the pathogenesis of PNH.

Purpose Our study examines how artificial intelligence (AI) can enhance decision-making processes to promote circular economy practices within the utility sector. Design/methodology/approach A unique case study of Alia Servizi Ambientali Spa, an Italian multi-utility company using AI for waste management, is analyzed using the Gioia method and semi-structured interviews. Findings Our study discovers the proactive role of the user in waste management processes, the importance of economic incentives to increase the usefulness of the technology and the role of AI in waste management transformation processes (e.g. glass waste). Originality/value The present study enhances the circular economy model (transformation, distribution and recovery), uncovering AI’s role in waste management. Finally, we inspire managers with algorithms used for data-driven decisions.

WESSI workshop at NYU Florence, World Bank, and WPSA 2017

In this paper, we examine how variations in normal tissue can influence disease classification of Raman spectra. Raman spectra from normal areas may be affected by previous disease or proximity to areas of dysplasia. Spectra were acquired in vivo from 172 patients and classified into five tissue categories: true normal (no history of disease), previous disease normal (history of disease, current normal diagnosis), adjacent normal (disease on cervix, spectra acquired from visually normal area), low grade, and high grade. Taking into account the various "normal" states of the tissue before statistical analysis led to a disease classification accuracy of 97%. These results indicate that abnormal changes significantly affect Raman spectra, even when areas are histopathologically normal. The sensitivity of Raman spectroscopy to subtle biochemical differences must be considered in order to successfully implement it in a clinical setting for diagnosing cervical dysplasia and cancer.

Epithelial cancers, including those of the skin and cervix, are the most common type of cancers in humans. Many recent studies have attempted to use Raman spectroscopy to diagnose these cancers. In this paper, Raman spectral markers related to the temporal and spatial effects of cervical and skin cancers are examined through four separate but related studies. Results from a clinical cervix study show that previous disease has a significant effect on the Raman signatures of the cervix, which allow for near 100% classification for discriminating previous disease versus a true normal. A Raman microspectroscopy study showed that Raman can detect changes due to adjacent regions of dysplasia or HPV that cannot be detected histologically, while a clinical skin study showed that Raman spectra may be detecting malignancy associated changes in tissues surrounding nonmelanoma skin cancers. Finally, results of an organotypic raft culture study provided support for both the skin and the in vitro cervix results. These studies add to the growing body of evidence that optical spectroscopy, in this case Raman spectral markers, can be used to detect subtle temporal and spatial effects in tissue near cancerous sites that go otherwise undetected by conventional histology.

Probiotic milk is a class of fermented milk that possesses health-promoting effects, not only due to the lactic acid bacteria (LAB) presence but potentially also to yeast activity. Hence, the aim of this work was to isolate and select yeasts from spontaneous milk fermentations to be used as inoculum, together with LAB, for manufacturing a potentially probiotic acidic low-alcohol fermented milk. Six yeast species were detected from the spontaneous milk fermentation. A screening of 13 yeast strains and 14 previously isolated LAB strains, based on the resistance to bile salts and to acidic conditions, was carried out. The best performing strains were successively tested for in vitro gastrointestinal tolerance. A strain of Kluyveromyces marxianus and a strain of Lactococcus lactis were selected for the manufacturing of two different fermented milk. The values of the main technological and microbiological parameters (pH, organic acids, ethanol, and microbial concentrations) of the experimental milk were in the range of those reported for this category of products. The evaluation of microorganism survival in fermented milk samples subjected to simulated gastrointestinal conditions highlighted a high resistance of both strains. In conclusion, the selected microbial starter culture enabled the setting up of potential probiotic fermented milk.

Seit einigen Jahren ist auch im deutschsprachigen Raum ein vermehrtes Interesse an einer Methodenfamilie zu beobachten, die generell unter dem Akronym ‚QCA’ bekannt ist. ‚QCA’ steht für ‚Qualitative Comparative Analysis’ und wurde von dem amerikanischen Sozialwissenschaftler Charles Ragin in den 1980er Jahren erstmals einer breiteren Öffentlichkeit zugänglich gemacht (Ragin 1987). Seitdem hat Ragin die Technik mehrmals modifiziert, erweitert und verfeinert (Ragin 2000; 2008b), so dass diese Familie der Datenanaly-severfahren mittlerweile einen hohen Bekanntheitsgrad erhalten hat. In diesem Beitrag stellen wir zuerst den ‚State of the Art’ hinsichtlich QCA vor und gehen dabei sowohl auf seine Grundprinzipien als auch auf die verschiedenen Varianten ‚konfigurativer vergleichender Methoden’ (Rihoux/Ragin 2008) ein. Danach unterbreiten wir eine Liste mit Kriterien für eine ‚gute’ QCA-Analyse. Dieser Beitrag soll somit AnwenderInnen von QCA als Richtlinie gelten, was sie bei der Durchführung einer QCA-Analyse beachten sollten, damit diese als qualitativ gut und technisch korrekt gelten kann. Darüber hinaus soll der von uns zur Diskussion gestellte Standard guter QCA-Praxis ein hilfreiches Instrument für LeserInnen und KommentatorInnen bei der Beurteilung von Arbeiten sein, die auf QCA beruhen.