Expatriate Performance Appraisal Management: The Use Of A 360-Degree Feedback At Nokia Telecommunications

Performance management systems are now being used as a comprehensive human resource management tool to evaluate the performance of employees through objective setting, performance appraisal and feedback, continuous training, and career development. The focal point of this article is Nokia Telecommunications, a multinational corporation with extensive experience in sending and receiving people on foreign assignments. The paper discusses performance management systems with a focus on appraisals for expatriates. Given performance appraisal challenges for expatriates, an overview assessment (using Nokia) is offered, a problem is highlighted, and a solution is presented.  From the analysis and findings, an alternative performance management system of appraisals is recommended for implementation with Nokia employees working abroad and other expatriates.

Affect dynamics in adolescent depression: Are all equilibria worth returning to?

Objective: Difficulties in emotion regulation during adolescence—a critical period for the development of these abilities—have been linked to depression. Early identification of deficits in emotion regulation may help prevent the onset of depression. This study investigated whether emotion regulation dynamics, particularly the speed of regulation to one’s affective equilibrium (damping) inferred from the Damped Oscillator Model (DOM), could predict future depressive symptoms in adolescents. We hypothesized that the relationship between damping and long-term outcomes would depend on the position of an individual's equilibrium. Methods: Participants (N = 115) aged 12-15 completed smartphone-based EMA for 30 days, rating six emotions four times daily. The DOM was applied to each participant's time series data, yielding person-specific frequency of oscillations (η) and damping (ζ) parameters. These parameters were then used to predict depressive symptoms at 6- and 12-month follow-ups controlling for baseline levels of depression. Results: Results revealed that the interaction between the damping parameter and the equilibrium position significantly predicted depressive symptoms for sadness, but not for other emotions. For individuals with higher equilibrium levels of sadness, stronger damping predicted higher follow-up depressive symptoms. Additionally, higher frequency of oscillation around the equilibrium – representing greater elasticity and less rigidity – of two emotions (interest and happiness) predicted fewer depressive symptoms. Conclusion: These findings suggest that the adaptive value of rapid emotional recovery depends on one's baseline emotional state. Tracking emotion regulation dynamics of both positive and negative emotions may improve our ability to identify adolescents at risk for depression before symptoms emerge, thereby informing targeted intervention and prevention efforts

Affect dynamics in adolescent depression: Are all equilibria worth returning to?

Objective: Difficulties in emotion regulation during adolescence—a critical period for the development of these abilities—have been linked to depression. Early identification of deficits in emotion regulation may help prevent the onset of depression. This study investigated whether emotion regulation dynamics, particularly the speed of regulation to one’s affective equilibrium (damping) inferred from the Damped Oscillator Model (DOM), could predict future depressive symptoms in adolescents. We hypothesized that the relationship between damping and long-term outcomes would depend on the position of an individual's equilibrium. Methods: Participants (N = 115) aged 12-15 completed smartphone-based EMA for 30 days, rating six emotions four times daily. The DOM was applied to each participant's time series data, yielding person-specific frequency of oscillations (η) and damping (ζ) parameters. These parameters were then used to predict depressive symptoms at 6- and 12-month follow-ups controlling for baseline levels of depression. Results: Results revealed that the interaction between the damping parameter and the equilibrium position significantly predicted depressive symptoms for sadness, but not for other emotions. For individuals with higher equilibrium levels of sadness, stronger damping predicted higher follow-up depressive symptoms. Additionally, higher frequency of oscillation around the equilibrium – representing greater elasticity and less rigidity – of two emotions (interest and happiness) predicted fewer depressive symptoms. Conclusion: These findings suggest that the adaptive value of rapid emotional recovery depends on one's baseline emotional state. Tracking emotion regulation dynamics of both positive and negative emotions may improve our ability to identify adolescents at risk for depression before symptoms emerge, thereby informing targeted intervention and prevention efforts

The Combination of Duvelisib, a PI3K-δ,γ Inhibitor, and Romidepsin Is Highly Active in Relapsed/Refractory Peripheral T-Cell Lymphoma with Low Rates of Transaminitis: Results of Parallel Multicenter, Phase 1 Combination Studies with Expansion Cohorts

Abstract Introduction: Most therapies for relapsed/refractory (rel/ref) T-cell lymphomas (TCLs) induce responses in about 25%-30% of pts. Phosphoinositide-3-kinase (PI3K) delta has a role in survival and proliferation of malignant T cells as well as T-cell receptor and cytokine signaling in nonmalignant T cells. Inhibition of PI3K gamma can reprogram macrophages and promote tumor phagocytosis. A phase I study of the PI3K-δ/γ inhibitor duvelisib (D) in pts with rel/ref TCLs showed promising activity, but high rates of grade (Gr) 3/4 ALT elevation at the MTD of 75 mg BID (Horwitz et al, Blood 2018). Based on in vitro evidence of synergy, we initiated a phase I/II study of D combined with either romidepsin (R) or bortezomib (B). Methods: Pts were enrolled into parallel phase I dose escalation arms utilizing a 3+3 design to define the maximum tolerated dose (MTD) of D combined with either R (Arm A) or B (Arm B) in cycle 1. D was dosed at 25 mg, 50mg, or 75 mg BID on days 1-28 with either R (10 mg/m2 on days 1, 8, &amp; 15) or B (1 mg/m2 on days 1, 4, 8, &amp; 11) each on 28-day cycles. Once the MTD was established with each combination, preplanned expansion cohorts were enrolled to further characterize safety and describe subtype-specific efficacy (PTCL and CTCL). Based upon promising safety and efficacy, a total of 39 pts were treated on Arm A (33 at the MTD, D 75 mg BID + R 10 mg/m2). All pts received prophylaxis against Varicella and Pneumocystis. Response assessments were performed q2 cycles for 6 months and then q3 cycles. To assess biomarkers of response and resistance to single-agent D, 10 pts in Arm A (75 mg BID) and 10 pts in Arm B (25 mg BID) were each treated with 1 cycle of D alone, with pretreatment and on-treatment biopsies. Pts who did not achieve CR on D alone at the end of cycle 1 proceeded to combination therapy. Results: The MTD was not reached in Arm A (R+D); thus, dose level 3(DL3); (D 75 mg BID + R 10 mg/m2 days 1, 8, &amp; 15) was deemed the MTD and used for expansion. In Arm B there were no cycle 1 DLTs. However, Gr 3 elevations of ALT or AST following cycle 2 were observed in 3 pts at DL2 (D 50mg BID) and 2 pts at DL3 (D 75mg BID) leading to DL1 (D 25mg BID + B 1mg/m2 days 1, 4, 8, &amp; 11) being accepted as MTD for expansion. Of Arm A pts at the MTD, 21/32 (65%) had adverse events (AEs) ≥Gr 3, possibly related to study drug. Events occurring in ≥10% of pts included: increased ALT/AST (n=5, 15%), neutropenia (n=6, 18%), and hyponatremia (n=4, 12%). Three pts had ≥Gr 3 diarrhea. There were no Gr 5 AEs related to protocol therapy. Strikingly, 4 of 5 pts with elevated transaminases (ALT [4], AST [1]) on combination began on the D-only Lead-In Arm at 75 mg BID. In contrast, only 1 of 22 (4%) pts receiving combination R+D in cycle 1 had Gr 3-4 transaminitis (p=.0242). Of the pts with Gr 3-4 diarrhea, 2 of 3 were on Lead-In (p=.0793). In Arm A, 35/39 pts were evaluable for response. Overall response rate (ORR) across all DLs was 51% (18/35) and CR rate (CR) was 17% (6/35). PTCL, ORR and CR rates were 55% (12/22) and 27% (6/22) respectively. Among CTCL, ORR was 46% (6/13), no CR. Reponses by histology are detailed in Table 1. Of these responders, 3 proceeded to allogeneic stem cell transplantation (allo SCT) with curative intent. Of note, 4 pts were not evaluable for response, described in Table 1. Median PFS for Arm A (all DL) was 8.8 m (PTCL) and 5.4 m (CTCL). Median follow up was 5.8 m, and median duration of response was 9.1 m. Of Arm B pts at the MTD, 10/22 (45%) had AEs ≥Gr 3, possibly related to study drug, of these, only neutropenia (n=4, 18%) occurred in ≥10% of pts at the MTD. There was 1 Gr 5 event, Stevens-Johnson syndrome, possibly related to protocol therapy. In Arm B, the ORR across all DLs was 32% (9/28), the CR rate was 11% (3/28). ORR in PTCL was 36% (5/14), 21% (3/14) achieved CR. ORR in CTCL was 28% (4/14), no CR. Responses by histology are detailed in Table 2. Of these responders, 1 proceeded to allo SCT with curative intent. Median PFS for Arm B (all DL) was 3.5 m (PTCL) and 4.6 m (CTCL). Median follow up was 7.2 m, and median duration of response was 9.3 m. Conclusion: Duvelisib in combination with romidepsin is highly active in pts with PTCL with tolerable side effects. Duvelisib can be safely combined with romidepsin at a 3-fold higher dose than with bortezomib (75 mg BID vs 25 mg BID) with much lower rate of Gr 3-4 transaminitis than single-agent duvelisib at the same dose. The high response rates and safety of Arm A (Duvelisib + Romidepsin) in PTCL appears to be a potential therapeutic advance and warrants further evaluation in a larger study. Disclosures Horwitz: Portola: Consultancy; Innate Pharma: Consultancy; Forty Seven: Consultancy, Research Funding; Kyowa-Hakka-Kirin: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Millennium/Takeda: Consultancy, Research Funding; Mundipharma: Consultancy; Corvus: Consultancy; Celgene: Consultancy, Research Funding; Infinity/Verastem: Consultancy, Research Funding; Aileron Therapeutics: Consultancy, Research Funding; Spectrum: Research Funding; Trillium: Consultancy. Moskowitz:Takeda: Honoraria; Incyte: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Bristol Myers-Squibb: Consultancy, Research Funding; Merck: Research Funding; ADC Therapeutics: Research Funding. Jacobsen:Seattle Genetics: Consultancy; Merck: Consultancy. Mehta-Shah:Spectrum: Consultancy; Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Genetech: Research Funding; Verastem: Research Funding. Khodadoust:Innate Pharma: Research Funding. Fisher:Seattle Genetics Inc.: Membership on an entity's Board of Directors or advisory committees; Genetech: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees. Kim:Medivir: Membership on an entity's Board of Directors or advisory committees; Portola: Research Funding; miRagen: Research Funding; Kyowa-Kirin-Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Neumedicine: Consultancy, Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Innate Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Tetralogic: Research Funding; Merck: Research Funding; Galderma: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Horizon Pharma: Consultancy, Research Funding; Forty Seven Inc: Research Funding; Soligenix: Research Funding; Eisai: Membership on an entity's Board of Directors or advisory committees, Research Funding. Weinstock:Travera: Equity Ownership; Astra Zeneca, JAX, Samumed, Regeneron, Sun Pharma, Prescient: Patents &amp; Royalties; Novartis, Dragonfly, Travera, DxTerity, Travera: Consultancy; Novartis, Astra Zeneca, Abbvie, Aileron, Surface Oncology, Daiichi Sankyo: Research Funding; Novartis: Consultancy, Research Funding; Genentech/Roche, Monsanto: Consultancy. </jats:sec

Clinical characteristics and outcome of central nervous system tumors harboring NTRK gene fusions

PURPOSE TRK fusions are detected in less than 2% of central nervous system tumors. There are limited data on the clinical course of affected patients. EXPERIMENTAL DESIGN We conducted an international retrospective cohort study of patients with TRK fusion-driven CNS tumors. RESULTS 119 patients were identified. The median age at time of diagnosis was 4.5 years. The majority were reported to have a histology consistent with a diagnosis of high-grade glioma (HGG) (57.1%) followed by low-grade glioma (LGG) (27.7%). Pediatric patients had a better prognosis with a median overall survival of 185.5 months compared to 24.8 months in adults (p<.0001). Patients with LGG also had a better outcome when compared to HGG (p=0.0012). The objective response was 68.8% with larotrectinib compared to 38.1% for non-targeted treatment. CONCLUSIONS Children with LGG glioma had a favorable outcome compared to adult and HGG. TRK inhibitors appear to improve tumor control

HGG-11. Clinical characteristics and clinical evolution of a large cohort of pediatric patients with primary central nervous system (CNS) tumors and tropomyosin receptor kinase (TRK) fusion.

Abstract BACKGROUND: TRK fusions are detected in less than 3% of CNS tumors. Given their rarity, there are limited data on the clinical course of these patients. METHODS: We contacted 166 oncology centers worldwide to retrieve data on patients with TRK fusion-driven CNS tumors. Data extracted included demographics, histopathology, NTRK gene fusion, treatment modalities and outcomes. Patients less than 18 years of age at diagnosis were included in this analysis. RESULTS: Seventy-three pediatric patients with TRK fusion-driven primary CNS tumors were identified. Median age at diagnosis was 2.4 years (range 0.0–17.8) and 60.2 % were male. NTRK2 gene fusions were found in 37 patients (50.7%), NTRK1 and NTRK3 aberrations were detected in 19 (26.0%) and 17 (23.3%), respectively. Tumor types included 38 high-grade gliomas (HGG; 52.1%), 20 low-grade gliomas (LGG; 27.4%), 4 embryonal tumors (5.5%) and 11 others (15.1%). Median follow-up was 46.5 months (range 3-226). During the course of their disease, a total of 62 (84.9%) patients underwent surgery with a treatment intent, 50 (68.5%) patients received chemotherapy, 35 (47.9%) patients received radiation therapy, while 34 (46.6%) patients received NTRK inhibitors (3 as first line treatment). Twenty-four (32.9%) had no progression including 9 LGG (45%) and 9 HGG (23.6%). At last follow-up, only one (5.6%-18 evaluable) patient with LGG died compared to 11 with HGG (35.5%-31 evaluable). For LGG the median progression-free survival (PFS) after the first line of treatment was 17 months (95% CI: 0.0-35.5) and median overall survival (OS) was not reached. For patients with HGG the median PFS was 30 months (95% CI: 11.9-48.1) and median OS was 182 months (95% CI 20.2-343.8). CONCLUSIONS: We report the largest cohort of pediatric patients with TRK fusion-driven primary CNS tumors. These results will help us to better understand clinical evolution and compare outcomes with ongoing clinical trials.</jats:p