Similar Negative Impact Research Articles

Do early‐treated adults with phenylketonuria sense high phenylalanine levels?

AbstractThis study aimed to analyze whether early‐treated adults with phenylketonuria (PKU) can subjectively sense high phenylalanine (Phe) concentrations and whether a possible impact of Phe on objective measures of cognitive performance and mood reflects patients' self‐perception. Data from the PICO study, a randomized, placebo‐controlled, double‐blind, crossover trial, were analyzed. Twenty‐eight adults with PKU received either Phe capsules or placebo in two 4‐week intervention periods in a randomized order, with a 4‐week washout in between. The median Phe level increased from 852 μmol/L (interquartile range: 345) to 1455 μmol/L (interquartile range: 369). Neuropsychological assessments were performed at four study visits. At the end of the last study visit, patients were asked whether they could discern the Phe intervention period. Seven of 28 (25%) patients stated that they could not discern between the Phe and the placebo period. Twenty‐one of 28 (75%) patients subjectively thought to sense high Phe levels. Of the 21 patients, 12 (57%) correctly identified the Phe period, whereas 9 (43%) received placebo at the time when they thought they would receive the high Phe load. Binomial tests showed that the probability of 12 out of 21 is p = 0.140, and 12 out of 28 is p = 0.113. The “Right‐Guess” group showed significantly higher Phe changes than the “Wrong‐Guess” group. Cognitive performance and standardized mood assessment did not significantly differ, and both groups reported similar subjective negative impact on cognition and mood. In conclusion, adults with early‐treated PKU cannot effectively identify high Phe levels, although some individuals may be able to perceive more pronounced increases in Phe levels.

MODELING THE IMPACT OF TECHNOLOGICAL DEVELOPMENT AND IMPORTS ON EMPLOYMENT IN RUSSIA

The aim of the paper is to assess the impact of technological development and international trade on the level and structure of employment in Russian regions for the period of 2005-2019. The structure of employment is measured in terms of education level, sectoral specialization, and gender of the employed population. The contribution of the work to the scientific literature is expressed in three aspects. First, we empirically estimate the relationship between imports and employment structure. Second, we attempt to econometrically identify the impact of technological development on several indicators of regional employment. Third, we consider the joint impact of technological development and international trade in the estimated models on employment due to the complementarity of these factors. Based on a systemic generalized method of moments we reveal that technological development has: 1) a positive effect on the share of the employed specializing in mining industry, in the activities of hotels and public catering; 2) a negative impact on the share of the employed with secondary vocational and secondary general education, in agriculture, logistics, health care sectors. In terms of demographic indicators, a similar negative impact of technological development on the employment rate of women and men was obtained. At the same time, with growing total imports in the regions the threat of job losses for the employed with secondary vocational and secondary general education, the urban population, as well as those specializing in healthcare sector increases. Expenditures on fundamental research through the innovative development of regions are a factor in job creation. Technological development and foreign economic openness of the region are associated with greater adaptation of the employed population to competition in international trade and technological development.

Removal of Pb(II), Cu(II), and Ag(I) from aqueous solutions using biochar derived by P-enriched water hyacinth

ABSTRACT A new synthesis was developed to prepare engineered biochar derived from phosphorous-rich water hyacinth. The statistical analysis indicated a significant correlation between P content and the removal rates of Pb (II), Cu (II), and Ag (I), revealing the pivotal role of enrich P in the biochar for heavy metals (HM) removal. SEM-EDX, XRD and FTIR analyses validated the presence of P functional groups on the surface of P-biochar. Batch experiments showed that the strong acidic initial solution negatively affected the adsorption of HM ions, and a similar negative impact was observed during Cu (II) adsorption under the high ionic strength conditions. Competitive adsorption experiment confirmed P-biochar’s resilience against competing metal ions during the adsorption of HM ions. Pb (II) and Ag (I) adsorption were primarily governed by precipitation/reduction, along with complexation reactions involving P functional groups. Cu (II) adsorption was dominated by complexation between Cu (II) and P functional groups.

Evaluating mental health awareness and attitudes among international students in Japan during the COVID-19 pandemic

ObjectivesInternational students in Japan face unique mental health challenges stemming from cultural and linguistic differences, potentially accentuated by the COVID-19 pandemic. However, research on the mental health of this demographic is scarce. This study aims to describe their mental health status, awareness of mental health resources, and attitudes toward seeking mental health support. MethodsThis study conducted analyses based on data collected though an online survey at a national university in Japan during October and November 2022. International students were surveyed about their mental health status, awareness, and attitude. Descriptive statistics and Chi-square tests were employed to examine the associations between survey responses and demographic variables. ResultsAmong the 116 surveyed participants, 6.9% reported experiencing poor mental health, 16.4% rated their mental health as fair, and 1.7% expressed uncertainly about their mental health status. Similarly, 4.3% indicated poor physical health, 21.6% rated their physical health as fair, and 0.9% expressed uncertainty about their physical health. Additionally, 16.4% felt that their mental health adversely affected their daily life and academics, and 12.1% believed that their physical health had a similar negative impact. Awareness of mental health resources was notably low, with only 25.9% of students being informed. Furthermore, limited awareness was observed among older students (χ2 = 8.176, p < 0.01), degree-seeking students (χ2 = 4.727, p < 0.05), and those from African countries (χ2 = 4.721, p < 0.05), compared to their counterparts. A total of 10.4% expressed reluctance to pursue informal mental health support, and 9.5% showed similar reservations about seeking formal support. ConclusionThe study underscores the critical need for targeted outreach and the development of accessible, culturally sensitive mental health interventions for international students in Japan. Enhancing awareness and accessibility of mental health resources can contribute to the wellbeing of this demographic, potentially improving academic outcomes and fostering a more inclusive, supportive environment for international students, thereby advancing international collaboration and understanding.

Evaluation of the m7-FLIPI in Patients with Follicular Lymphoma: FOXO1 Mutational Status May be a Predictive Marker of Early Progression and Long-Term Outcome

DISCUSSION In pts with follicular lymphoma (FL) who received chemoimmunotherapy (CIT) as first-line treatment, progression of disease within 24 months of diagnosis (POD24) was associated with increased risk of death (Casulo, 2015). A clinicogenetic risk model that includes the mutation status of 7 genes ( EZH2, ARID1A, MEF2B, EP300, FOXO1, CREBBP, and CARD11), FLIPI and ECOG, known as the m7-FLIPI, was shown to improve risk stratification in frontline pts with advanced stage FL treated with CIT (Pastore, 2015), as well as predict POD24 after first-line CIT (Jurinovic, 2016). With the hypothesis that there are distinguishing features in the mutational landscape between pts with FL who experience POD24 vs those who don't, we evaluated the prognostic utility of the m7-FLIPI and its components in a retrospective series. MSK-IMPACT Heme (Ptashkin, 2019) is a 468 targeted gene panel that includes the 7 genes required to calculate the m7-FLIPI. We identified all pts with FL, grade 1-3A, who had IMPACT testing, excluding pts with FL grade IIIB, mixed histology, or de novo transformation at diagnosis (n = 295). Three pts were excluded for inadequate clinical data (n = 292). The m7-FLIPI was calculated as previously described. Progression-free survival (PFS) was calculated from date of diagnosis till date of progression after first-line treatment, death, or censored at date of last follow-up. Overall survival (OS) was calculated from date of diagnosis till death or censored at date of last follow-up. Cox proportional hazard models were used to compare differences in survival and the Fisher's exact test for categorical variables in SAS 9.4. A cohort of 292 pts was analyzed. Genomic alterations were identified in the 7 genes . Median age of diagnosis was 57 years (range 26-92) with a slight male predominance (53%). The median follow-up was 5.2 years (95% CI, 4.6-5.7). Initial treatment included monoclonal antibody + chemotherapy (57%), single-agent rituximab (17%), chemotherapy (2%), radiotherapy alone (8%), and other treatments (5%). Thirty-four pts (12%) were never treated. Out of 292 pts, 86 (29%) were high-risk by FLIPI and 42 (14%) were high-risk m7-FLIPI. Forty-four out of 86 pts with high-risk FLIPI (51%) were reclassified as low-risk by the m7-FLIPI. High-risk FLIPI was associated with shorter PFS (HR 1.54, 95% CI 1.12 - 2.11, p = 0.0085) and OS (HR 3.73, 95% CI 1.74 - 7.98, p = 0.0007). High-risk m7-FLIPI was associated with shorter PFS (HR 1.55, 95% CI 1.05 - 2.28, p = 0.027) but not OS (HR 2.09, 95% CI 0.92 - 4.76, p = 0.08). C-statistics showed that m7-FLIPI did not outperform FLIPI alone as a prognostic tool for PFS (FLIPI c-statistic = 0.55, 95% CI 0.51 - 0.59; m7-FLIPI c-statistic = 0.53, 95% CI 0.50 - 0.56) or OS (FLIPI c-statistic = 0.68, 95% CI 0.58 - 0.78; m7-FLIPI c-statistic = 0.55, 95% CI 0.47 - 0.63). Mutations in ARID1A as a single factor were associated with shorter PFS (HR 1.52, 95% CI 1.01-2.29, p=0.047), but this association did not remain significant after adjusting for FLIPI and ECOG (HR 1.49, 95% CI 0.97-2.28, p=0.07). Mutations in FOXO1 were associated with shorter PFS (HR 1.48, 95% CI 1.00-2.19, p=0.049) and OS (HR 2.65, 95% CI 1.21-5.79, p=0.015) as a single factor. This association remained significant after adjusting for FLIPI and ECOG: PFS (HR 1.60, 95% CI 1.08-2.37, p=0.020) and OS (HR 2.65, 95% CI 1.21-5.83, p=0.015; Table 1). High-risk m7-FLIPI and FLIPI pts were not more significantly likely to experience POD24, OR 1.44, 95% CI 0.73-2.83, p=0.37 for m7-FLIPI and 1.48, 95% CI 0.87-2.51, p=0.17 for FLIPI. Pts with mutated FOXO1 were more likely to experience POD24, OR 2.47, 95% CI 1.29-4.71, p=0.008. The m7-FLIPI neither improved risk stratification compared to FLIPI nor did it predict POD24 in this series. Mutations in FOXO1 were associated with shorter PFS and OS independent of FLIPI and ECOG. Pts with mutated FOXO1 were enriched among those with POD24, suggesting that FOXO1 mutation may be a predictive marker for early failure of first-line treatment and death, including pts not fulfilling the POD24 criteria. Similar negative impact of FOXO1 was reported in a comprehensive genomic analysis of FL (Mozas, 2023). Both series are limited by patient numbers. Additional efforts to confirm this observation may be useful for understanding the mechanisms behind the prognostic effect of POD24 on survival and improving long-term outcome in this high-risk FL group.

SDPS-09 MIXED RESPONSE OF BRAIN METASTASES TREATED WITH OSIMERTINIB PREDICTS INFERIOR SURVIVAL OUTCOMES: AN ARTIFICIAL INTELLIGENCE-BASED LESION-LEVEL ASSESSMENT FOR CRANIAL CONTROL OF EGFRMUTANT NONSMALL CELL LUNG CANCER

Abstract Osimertinib has been found to be effective for intracranial control in patients with metastatic EGFR-mutant non-small cell lung cancer (NSCLC). However, the lesion-level response of brain metastases to osimertinib has not been thoroughly evaluated. This retrospective study included 73 patients with EGFR-mutant NSCLC and brain metastases who were treated with osimertinib at a single institution from 2016 to 2021. Patients with the leptomeningeal disease were excluded. The study used an FDA-approved brain tumor management artificial intelligence (AI) platform, VBrain, to identify, track, and measure brain metastases on the baseline and follow-up MRI brain scans. Mixed response (MiR) was defined as the occurrence of progressive or new lesions along with synchronous responsive shrinking intracranial lesions at the first follow-up scan. K-means grouping was used to partition patients into two clusters according to their response heterogeneity. With a median follow-up of 23.8 months, a high MiR score (higher than 103%, n=25) was associated with worse cranial-progression-free survival (3.2 vs. 17.9 months, p&amp;lt;0.0001) and significantly inferior overall survival (12.4 vs. 30.1 months, HR=2.35, p=0.016). This poses a similar negative impact on the survivals of 18 patients with pure RANO-BM progression (HR=2.52, p=0.025). Eight patients had the highest MiR score (MiRmax), in whom synchronous new lesions and completely responsive tumors were observed. In a multivariate Cox proportional-hazards regression involving performance status, extracranial failure, tumor volume, lesion number, and RANO-BM classification as variables, MiRmax remained an independent prognosticator for inferior survival (HR=5.20, 95%CI; 2.21–12.23, p=0.002). Our study demonstrates that MiR in brain metastases from EGFR-mutant NSCLC treated with osimertinib is associated with inferior survival outcomes and a higher risk of local progression. Lesion-level response assessment using AI may provide important prognostic information and aid in treatment decision-making for these patients.

Unconventional monetary policy and debt sustainability in Japan

We adapt to the Japanese case a model of stochastic debt sustainability within a monetary policymaking framework. The model incorporates the effects of unconventional monetary policy and its potential unwinding on sovereign debt dynamics. A scenario tree represents stochastic and correlated macroeconomic and fiscal variables, and a coherent risk measure allows to draw probabilistic inferences on sustainability. We calibrate the model to the Quantitative and Qualitative Easing (QQE) that Bank of Japan launched in 2013. Using a retrospective analysis, we find a large favourable effect of the QQE on sovereign debt dynamics. Forward-looking simulations under different exit strategies show that the termination and unwinding of the QQE could raise debt sustainability concerns. A sharp tightening of global financial conditions could have a similar negative impact on debt dynamics, requiring a fiscal adjustment to keep debt sustainable.

Commodity price uncertainty and international trade

Abstract We empirically investigate the impact of commodity price uncertainty on US and Euro Area (EA) trade flows. Our results indicate that the response of US and EA trade flows to commodity uncertainty shocks is larger, in magnitude and persistence, when compared with the respective impact of commodity supply and demand shocks. Moreover, our analysis shows that a one-standard deviation shock in commodity price volatility has a higher (in magnitude) and more persistent effect on trade when compared with the respective shocks in exchange rates and commodity prices. Finally, an uncertainty shock in various agricultural and metals markets has a similar negative impact on trade flows to that of energy uncertainty shocks.

Anomia in left hemisphere stroke, multiple sclerosis and Parkinson’s disease – a comparative study

Purpose To explore quantitative and qualitative features of anomia in participants with left-hemisphere stroke, Parkinson’s disease, or multiple sclerosis. Materials and methods This descriptive cross-sectional study compares signs of anomia within and across participants (n = 87), divided into four groups; moderate to severe anomia after stroke (MSAS, n = 19), mild anomia after stroke (MAS, n = 22), PD (n = 19) and MS (n = 27). Aspects analysed include naming accuracy and speed, the nature of incorrect responses, semantic and phonemic verbal fluency, information content in re-telling, and the relationship between test results and self-reports on word-finding difficulties and communicative participation. Results All groups had impaired verbal fluency, prolonged response times and reduced information content in re-telling. The MSAS group had significantly more signs of anomia than the other groups. Results from the other groups overlapped on a MAS—PD—MS continuum. Both semantically and phonologically incorrect responses were common in the stroke groups, while semantically incorrect ones predominated in the PD and MS groups. All four groups reported a similar negative impact on self-perceived communicative participation. Correlations between self-reports and test results were inconsistent. Conclusions Anomia features have quantitative and qualitative similarities and differences across neurological conditions.

Understanding of the dynamics of mobile reading: An HMM model of user engagement and content consumption

AbstractUnderstanding consumers’ engagement and subsequent content consumption behavior in the mobile context is critical to mobile app providers. In this paper, we develop a Hidden Markov Model (HMM) to capture the dynamics of users’ engagement states and consumption decisions on the number of books/chapters read and the amount of money spent. Our method allows us to simultaneously capture three interdependent usage behaviors using a single integrated model and identify the impact of content loading time and previous reading behavior on users’ engagement dynamics and content consumption. We calibrate the model using a tap stream data set of individual users’ reading activities on a mobile app. Our analysis reveals three distinct engagement states, a low state with inactive users, a medium state with users sampling books, and a high state with users reading intensively. Furthermore, we find that content loading time has higher negative impacts on high‐state users in state transitioning than medium‐state users. In contrast, the days that elapsed since the last visit has a similar negative impact on the users in the high and medium states. The effect of usage frequency on users in state transitioning is always positive. We have also identified the weekend effect and social influence on users’ reading outcomes. Finally, our simulations quantify the shortened content loading time and the days elapsed since the last visit on users’ engagement dynamics and content consumption decisions, which generate important managerial implications for app providers.

The effect of temporary workers and works councils on process innovation

PurposeThis study aims to investigate the effects of temporary workers and works councils on process innovations at manufacturing sites. The impact of temporary workers, commonly viewed as a means of operational flexibility and cost savings, on firms’ ability to innovate is underexplored. Works councils represent and help integrate temporary workers, but are often equated with unions, which have been criticized as barriers to innovation, especially in the US.Design/methodology/approachThe authors use secondary data collected by the Institute for Employment Research (IAB) of the German Federal Employment Agency. Specifically, the authors conduct a series of regression analyses using 11-year panel data covering the period 2009–2019 with 11,641 manufacturing site-year observations.FindingsThe results suggest that the use of temporary workers initially promotes process innovation, but at too high a level, it impairs firms’ ability to innovate. Furthermore, the results suggest that works councils have a positive impact on innovation and dampen the curvilinear effect found with respect to temporary workers.Originality/valueResearch has largely focused on the cost and flexibility benefits of temporary workers. The authors analyze the effectiveness of temporary workers in terms of innovativeness. By including works councils, the study also consider the contextual environment in which temporary workers are employed. Finally, the results reject the assumption that works councils have a similar negative impact as unions on innovation; in fact, the authors find the opposite.

An economic repercussion to the impact of climate change on the most important Egyptian food security crops

We examine how the Climate Change affected on the Agricultural Production , and how the impact of climatic changes on the productivity of the most important grain crops in Egypt, with the aim of determining the extent to which productivity has changed due to climate change in Egypt, using the Autoregressive Distributed lagged methodology (ARDL), where it was found that there is an inverse relationship between climate changes and the productivity of the most important cereal crops, a relationship that is consistent with the economic logic. The results indicate that a similar negative impact of the maximum temperature change on the productivity of the most important cereal crops in the long term, which is consistent with an economic theory.

Not Just Time on Social Media: Experiences of Online Racial/Ethnic Discrimination and Worse Sleep Quality for Black, Latinx, Asian, and Multi-racial Young Adults.

Sleep quality in young adulthood sets the stage for long-term health. Racial/ethnic sleep disparities between White college-attending young adults and college-attending young adults of color exist. The stress of experiencing racial/ethnic discrimination makes it difficult for college-attending young adults of color to get good quality sleep. Yet it remains unclear if experiencing online racial/ethnic discrimination also has consequences for sleep quality, and if this association may vary by frequency of social media use. To investigate the role of racial/ethnic discrimination on sleep quality, we conducted an online survey of 154 college-attending young adults (Mage = 19.51) who identified as Black (42.2%), Latinx (16.9%), Asian (20.8%), or Bi-/multi-racial (20.1%) from a predominantly White university. Results indicated that more exposure to racial/ethnic discrimination was associated with worse sleep quality for young adults of color. Results suggest that online racial/ethnic discrimination has a similar negative impact on sleep quality regardless of the frequency of social media use. Increased attention to negative race-related experiences online as one potential risk factor for poor long-term health for young adults of color is needed, regardless of how many hours they spend on social media. Structural interventions, screening for stress due to exposure to online racial/ethnic discrimination, and facilitating opportunities to prepare for this exposure may be an important priority for sleep health and reduction of racial/ethnic health disparities.

Eating disorders in the era of the COVID-19 pandemic.

COVID-19 pandemic and its socio-economic consequences have been influencing considerably the Greek population and especially those people that are vulnerable or are actually suffering from a mental disorder. Considering eating disorders (ED) there are reports of a number of factors that increase the stress experienced by patients. The most important of them are:1 A. Quarantine and house confinement. Many ED patients report poor relationships with other family members or in some cases falling victims of some type of abusive behavior by other family members. Prolonged compulsory house confinement could have a negative impact in the course of ED. It should be noted that a similar negative impact of the pandemic has been observed in family members that have unsuccessfully tried to balance the need of the patients with the need of the rest of the family. B. Changes in exercising. Quarantine has severely influenced patients that have been doing vigorous and compulsive exercise. C. Food fear. During the first quarantine in March 2020, there were rumors of forthcoming extreme shortages of necessary products and food. D. Restrictions in the access to mental health facilities and therapists. In many countries, a substantial number of mental health programs were temporarily shut down during the first wave of the pandemic. E. Isolation of people residing alone in cities far away from the family home. F. Financial adversities due to slow down of economic activities causes by quarantine. g. Increase in obsessive fear concerning body health and food purity due to orthorexia nervosa onset or relapse.2 Research conducted during the pandemic showed that women suffering from ED reported more often than men increase in ED symptomatology, in the number of hours spent exercising and in the intensity of preoccupation with their body image and social appearance.2 A meta-analysis of ED studies during the pandemic showed that 65% of the patients reported a deterioration of ED symptomatology.3 Contrary to the above, the longitudinal studies that were included in the meta-analysis did not report any substantial difference in BMI and ed symptomatology before and after the first quarantine.3 Anorexia nervosa patients seemed to be more influenced than patients suffering from bulimia nervosa and ED non otherwise specified.3 Other longitudinal studies reported that bulimia nervosa patients were greatly influenced during the quarantine showing signs of slower remission or even relapse of the bulimic symptoms.4 Family conflict and intense fear for the life of loved ones could predict a relapse of the ED symptomatology.4 Young people were often caught in the following dilemma. On the one hand, consumption of palatable food could be used as a coping mechanism for regulating emotions such as anxiety, sorrow, and loneliness caused by prolonged house isolation. On the other hand, the increasing presence in the virtual reality environment of social networks has intensified the need for a perfect slim and fit body that could attract more followers and ensure social approval and success.5,6 A special interest group that was affected by the pandemic, was university students. ED symptomatology increased, especially among female students. Stress and depression related to social isolation and disruption of educational activities have been correlated with ED manifestation, especially bulimia nervosa.7 Fortunately, young patients seem to adjust adequately to internet-based treatments. There are indications that therapy through teleconference could prove quite effective for the treatment of ED.8 There are reports that this type of treatment is not attractive for anorexia nervosa patients, while all other ED patients are well adjusted to it.1 The consequences of the pandemic considerably affected mental health experts that have been treating ED patients as the number of new and relapsed clients raised dramatically. The situation was worsened by the fact that a large number of those patients had to be treated distantly. It has been reported that often conduct with other colleagues, the feeling of higher purpose or duty, recognition of their effort and supervision are some of the factors that can protect therapists from professional burn-out.1.

The determinants of demand for tourism in Turkey: Does terror-threat matter? A Markov Regime Switching-VAR approach

Abstract This paper investigates the impacts of potential determinants of demand for tourism in Turkey through Markov Regime Switching-Vector Auto Regression (MS-VAR) estimations from 1999 to 2017 on monthly data. The determinants are income level, exchange rates and the threat of terror incidences. The terror variable, following the Global Terrorism Index (GTI) 2017 report, is calculated for Turkey by the author. This research has conducted two separate MS-VAR models to observe the relevant parameters’ signs of the demand for tourism function. Both MS-VAR models revealed that income level and exchange rates have positive influences on tourism while the terror threat has a negative impact on tourism in Turkey. Terror adversely affects the demand for tourism in the short-term in which terror has occurred in the nearest past (i.e., a month ago). The MS-VAR models also yield that a similar negative impact of terror on tourism activities does not appear over the longer periods.

P-179: Immunoparesis remains a negative prognostic factor in newly diagnosed Multiple Myeloma by competing risk analysis

<h3>Background</h3> Recent reports describe worst outcome in patients with multiple myeloma (MM) and immunoparesis (IP). However, infections can be considered a competing event when analyzing the impact of IP on overall survival (OS). Here, we analyzed the prognostic impact of IP in newly diagnosed MM (NDMM) with a different approach. <h3>Methods</h3> This is a single-center retrospective study of NDMM patients diagnosed between 2000 to 2018. We defined IP as suppression of both uninvolved polyclonal immunoglobulins in IgG and IgA MM or three uninvolved polyclonal immunoglobulins in light-chain MM. <h3>Results</h3> A total of 651 patients with NDMM were diagnosed and treated at our institution. Median age at diagnosis was 65 years old (56 – 74). The M-protein isotype was IgG in 355 (55%) patients, IgA in 184 (28%), light – chain in 98 (15%) and IgD in 14 (2%). At diagnosis, IP was present in 318 (47%) patients, and increased with each ISS stage (37% in ISS-1, 54% in ISS-2 and 63% in ISS-3; p<0.01). 347 (53%) patients were fit for autologous stem cell transplant (ASCT). With a median follow-up of 5 years, median PFS in patients with IP was shorter compared to those without IP (22 vs. 27 months; p<0.01). Cox univariate analysis for known risk factors of progression showed that high β2-microglobulin (≥3.5 mg/L, HR 1.4; p<0.01), low serum albumin (< 35 g/L, HR 1.2; p=0.1), high LDH (≥ 450 U/L, HR 1.6; p<0.01) and IP (HR 1.3; p<0.01) had similar negative impact on PFS. Multivariate analysis showed that high β2-microglobulin, high LDH and IP were the main risk factors with independent negative impact on PFS. Given this data, we aimed to create a prediction model on PFS by two different approaches. The first one consisted of evaluating all possible equations (Stata 16.0. College Station, TX) with AIC and C-Harrell as main criteria, and the second used backward stepwise elimination process. Both resulted in a parsimonious model that contained high β2-microglobulin, high LDH and IP. At the time of this analysis, 45% patients were still alive. Severe infection as a cause of death was seen in 7% patients. Cox univariate analysis showed that patients with IP at diagnosis had negative impact on OS (HR 1.2; p=0.04). To evaluate the impact of IP on OS, we included severe infections deaths as competing events. With this approach, risk of death among patients with or without IP did not change significantly, maintaining its prognostic value both in eligible and non-eligible patients for ASCT (Peppe and Mori test; p=0.12 and p=0.08 respectively). These results suggest that severe infections do not play a major role in OS of patients with NDMM and IP. <h3>Conclusion</h3> In patients with NDMM, IP is an important negative biomarker with shorter median PFS. Its prognostic impact was similar to other known potent risk factors of progression. Regarding OS, IP kept its negative impact even in the presence of severe infections deaths as competing events.

COVID-19 pandemic and connectedness across financial markets

Purpose This study aims to estimate the time–frequency connectedness among global financial markets. It draws a comparison between the full sample and the sample during the COVID-19 pandemic. Design/methodology/approach The study uses the connectedness framework of Diebold and Yilmaz (2012) and Barunik and Krehlik (2018), both of which consider time and frequency connectedness and show that spillover is specific to not only the time domain but also the frequency (short- and long-run) domain. The analysis also includes pairwise connectedness by making use of network analysis. Daily data on the MSCI World Index, Barclays Bloomberg Global Treasury Index, Oil future, Gold future, Dow Jones World Islamic Index and Bitcoin have been used over the period from May 01, 2013 to July 31, 2020. Findings This study finds that cryptocurrency, bond and gold are hedges against both conventional stocks and Islamic stocks on average; however, these are not “safe havens” during an economic crisis, i.e. COVID-19. External shocks, such as COVID-19, strengthen the return connectedness among all six financial markets. Research limitations/implications For investors, the study provides important insights that during external shocks such as COVID-19, there is a spillover effect, and investors are unable to hedge risk between conventional stocks and Islamic stocks. These so-called safe haven investment alternatives suffer from the similar negative impact of systemic financial risk. However, during an external shock such as COVID-19, cryptocurrencies, bonds and gold can be used to hedge risk against conventional stocks, Islamic stocks and oil. Moreover, the findings imply that by engaging in momentum trading, active investors can gain short-run benefits before the market processes any new information. Originality/value The study contributes to the emergent literature investigating the connectedness among financial markets during the COVID-19 pandemic. It provides evidence that the return connectedness among six global financial markets, namely, conventional stocks, Islamic stocks, bond, oil, gold and cryptocurrency, is extremely strong. From a methodological standpoint, this study finds that COVID-19 pandemic shock has a significant short-run impact on the connectedness among financial markets.

HLA-A alleles influencing NK cell function impact AML relapse following allogeneic hematopoietic cell transplantation

AbstractHLA-B allotypes exhibiting the Bw4 epitope trigger variable inhibitory signaling of KIR3DL1 receptor types, where strong inhibitory HLA-B and KIR3DL1 allele combinations are associated with increased risk for relapse of acute myelogenous leukemia (AML) following allogeneic hematopoietic cell transplantation (HCT). Several HLA-A allotypes also exhibit the Bw4 epitope. Studies with natural killer (NK) cell clones have demonstrated NK inhibition via KIR3DL1 by HLA-A Bw4+ allotypes, but did not delineate strengths of inhibition or hierarchies of NK education. Using primary NK cells from healthy donors, we demonstrate that HLA-A*23, HLA-A*24, and HLA-A*32 proteins are expressed at different densities and exhibit different capacities to educate and inhibit KIR3DL1-expressing NK cells in vitro. Among the HLA-A Bw4+ allotypes, HLA-A*24 and HLA-A*32 demonstrate the strongest inhibitory capacity. To determine if HLA-A allotypes with strong inhibitory capacity have similar negative impact in allogeneic HCT as HLA-B Bw4+ allotypes, we performed a retrospective analysis of 1729 patients with AML who received an allogeneic HCT from a 9/10 or 10/10 HLA allele-matched unrelated donor. Examination of the donor-recipient pairs whose Bw4 epitope was exclusively contributed from HLA-A*24 and A*32 allotypes revealed that patients with HLA-A*24 who received an allograft from a KIR3DL1+ donor experienced a higher risk of disease relapse (hazard ratio, 1.65; 95% confidence interval, 1.17-2.32; P = .004) when compared with patients without a Bw4 epitope. These findings indicate that despite weak affinity interactions with KIR3DL1, common HLA-A allotypes with the Bw4 epitope can interact with KIR3DL1+ donor NK cells with clinically meaningful impact and provide additional insight to donor NK alloreactivity in HLA-matched HCT.

Similar negative emotional impact on hair loss in neoadjuvant endocrine therapy compared to neoadjuvant chemotherapy in young women with breast cancer from patient reported outcomes.

e19242 Background: We aimed to evaluate patient-reported outcomes (PROs) in the NEST phase III trial, in which neoadjuvant endocrine therapy (NET) compared to conventional neoadjuvant chemotherapy (NCT) for hormone-responsive lymph node-positive premenopausal breast cancer. Methods: Premenopausal women with estrogen receptor (ER)-positive, HER2-negative, and lymph node-positive premenopausal breast cancer patients were enrolled. Patients were randomized to either 24 weeks of neoadjuvant chemotherapy with doxorubicin plus cyclophosphamide followed by taxane (T) or neoadjuvant endocrine therapy with goserelin and tamoxifen. PROs were assessed at day 1 (baseline) and at the end of treatment, using the breast cancer module of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 23 (EORTC QLQ BR23). ClinicalTrials.gov: NCT01622361. Results: 187 patients were randomly assigned to chemotherapy (n=95) or endocrine therapy (n=92), and 174 patients completed the 24 weeks of neoadjuvant treatment period (n=87, both). Baseline scores were similar between arms. No statistically significant between-treatment differences were observed for the function scales including body image, sexual functioning, and sexual enjoyment although endocrine treatment showed significant improvement in future perspective (HR=8.3, 95% CI:1.72-18.38; P=0.021). Even though no alopecia was reported in NET group, no statistically significant difference between both arms in the “upset by hair loss” was observed, in which NET group showed even worse score. Conclusions: Patients who received NET had significant improvement in a future perspective, however, a similar emotional negative impact on hair loss was observed compared with NCT despite no reported alopecia. Key words: breast cancer, patient-reported outcomes, quality of life, hair loss, EORTC QLQ-BR 23. Clinical trial information: NCT01622361 .

Neoadjuvant endocrine therapy versus neoadjuvant chemotherapy in young women with breast cancer: Prognosis and axillary node surgery.

e12626 Background: We aimed to evaluate patient-reported outcomes (PROs) in the NEST phase III trial, in which neoadjuvant endocrine therapy (NET) compared to conventional neoadjuvant chemotherapy (NCT) for hormone-responsive lymph node-positive premenopausal breast cancer. Methods: Premenopausal women with estrogen receptor (ER)-positive, HER2-negative, and lymph node-positive premenopausal breast cancer patients were enrolled. Patients were randomized to either 24 weeks of neoadjuvant chemotherapy with adriamycin plus cyclophosphamide (AC) followed by taxane (T) or neoadjuvant endocrine therapy with zoladex and tamoxifen. PROs were assessed at day 1 (baseline) and at the end of treatment, using the breast cancer module of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 23 (EORTC QLQ BR23). ClinicalTrials.gov: NCT01622361. Results: 187 patients were randomly assigned to chemotherapy (n = 95) or endocrine therapy (n = 92), and 174 patients completed the 24 weeks of neoadjuvant treatment period (n = 87, both). Baseline scores were similar between arms. No statistically significant between-treatment differences were observed for the function scales including body image, sexual functioning, and sexual enjoyment although endocrine treatment showed significant improvement in future perspective (HR = 8.3, 95% CI:1.72-18.38; P= 0.021). Even though no alopecia was reported in NET group, no statistically significant difference between both arms in the “upset by hair loss” was observed, in which NET group showed even worse score. Conclusions: Patients who received NET had significant improvement in a future perspective, however, a similar emotional negative impact on hair loss was observed compared with NCT despite no reported alopecia. Key words: breast cancer, patient-reported outcomes, quality of life, hair loss, EORTC QLQ-BR 23. Clinical trial information: NCT01622361.