Certainty Equivalent Planning for Multi-Product Batch Differentiation: Analysis and Bounds

We consider a multi-period planning problem faced by a firm that must coordinate the production and allocations of batches to end products for multiple markets. Motivated by a problem faced by a biopharmaceutical firm, we model this as a discrete-time inventory planning problem where in each period the firm must decide how many batches to produce and how to differentiate batches to meet demands for different end products. This is a challenging problem to solve optimally, so we derive a theoretical bound on the performance of a Certainty Equivalent (CE) control for this model, in which all random variables are replaced by their expected values and the corresponding deterministic optimization problem is solved. This is a variant of an approach that is widely used in practice. We show that while a CE control can perform very poorly in certain instances, a simple re-optimization of the CE control in each period can substantially improve both the theoretical and computational performance of the heuristic, and we bound the performance of this re-optimization. To address the limitations of CE control and provide guidance for heuristic design, we also derive performance bounds for two additional heuristic controls -- (1) Re-optimized Stochastic Programming (RSP), which utilizes full demand distribution but limits the adaptive nature of decision dynamics, and (2) Multi-Point Approximation (MPA), which uses limited demand information to model uncertainty but fully capture the adaptive nature of decision dynamics. We show that although RSP in general outperforms the re-optimized CE control, the improvement is limited. On the other hand, with a carefully chosen demand approximation in each period, MPA can significantly outperform RSP. This suggests that, in our setting, explicitly capturing decision dynamics adds more value than simply capturing full demand information.http://deepblue.lib.umich.edu/bitstream/2027.42/116386/1/1296_Ahn.pd

Role of Immunohistochemistry in Fine Needle Aspiration and Core Needle Biopsy of Thyroid Nodules

Objectives Immunohistochemistry (IHC) has been used for the diagnosis of indeterminate results in fine needle aspiration (FNA) of thyroid nodules. However, the role of IHC in core needle biopsy (CNB) is not clear and the efficacy of testing for molecular markers following CNB has not been evaluated. The aim of this study is to compare the role of IHC staining in CNB with that in FNA when examining thyroid nodules and to compare the sensitivity and usefulness of different molecular markers. Methods Consecutive cases of thyroid FNA and CNB accompanied by IHC from 2004 to 2014 were included in this study with retrospective review of medical record. The rate of remaining nondiagnostic result (unsatisfactory, atypia of undetermined significance or follicular lesion of undetermined significance [AUS/FLUS]) and rate of strong expression of each molecular marker according to the diagnosis were evaluated. Results IHC was more frequently performed in CNB with multiple molecular markers compared to FNA (38.1% vs. 2.8%, 3 or 4 markers [Gal-3, HBME-1, CK19, and CD56] vs. 1 marker [Gal-3]). In the CNB group, 11.3% remained as AUS/FLUS after IHC, and the rate remaining nondiagnostic was significantly less than in the FNA group (42.9%). Gal-3 and CK19 showed higher specificity and expressed mainly in conventional type of papillary carcinoma and HBME-1 showed higher sensitivity for the diagnosis of carcinoma with expression in both conventional type and follicular variant papillary thyroid carcinoma. Conclusion With these data, we could conclude that IHC was more effective following CNB than following FNA

Results of Free Flap Reconstruction After Ablative Surgery in the Head and Neck

ObjectivesDue to the complex anatomy and function of the head and neck region, the reconstruction of ablative defects in this area is challenging. In addition, an increasing interest in improving the quality of life of patients and achieving good functional results has highlighted the importance of free flaps. The aim of this study was to summarize the results of free flap reconstruction and salvage of free flaps in a single institute, and to analyze differences in the results by the flap donor site, recipient site, and learning curve.MethodsThe medical records of patients who underwent free flap reconstruction from 2004-2012 were reviewed retrospectively. One hundred and fifty free flaps were used in 134 patients, who had an average age of 57.7 years. The types of flaps applied, primary defect sites, success rates, results of salvage operations for compromised flap, and the learning curve were analyzed.ResultsThe anterolateral thigh flap was preferred for the reconstruction of head and neck defects. The overall success rate was 90.7%, with 14 cases of failure. A total of 19 salvage operations (12.7%) for compromised flap were performed, and 12 flaps (63.2%) were salvaged successfully. Dependency on the facial vessels as recipient vessels was statistically different when oral and oropharyngeal defects were compared to hypopharyngeal and laryngeal defects. The learning curve for microvascular surgery showed decrease in the failure rate after 50 cases.ConclusionThe free flap technique is safe but involves a significant learning period and requires careful postoperative monitoring of the patient. Early intervention is important for the salvage of free flaps and for lowering the failure rate

Neck control after definitive radiochemotherapy without planned neck dissection in node-positive head and neck cancers

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to evaluate neck control outcomes after definitive radiochemotherapy without planned neck dissection in node-positive head and neck cancer.</p> <p>Methods</p> <p>We retrospectively reviewed medical records of fifty patients with node-positive head and neck cancer who received definitive radiochemotherapy. Twelve patients subsequently underwent neck dissection for suspicious recurrent or persistent disease. A median dose of 70 Gy (range 60-70.6) was delivered to involved nodes. Response evaluation was performed at a median of 5 weeks after completion of radiotherapy.</p> <p>Results</p> <p>Neck failure was observed in 11 patients and the 3-year regional control (RC) rate was 77.1%. Neck dissection was performed in 10 of the 11 patients; seven of these cases were successfully salvaged, and the ultimate rate of neck control was 92%. The remaining two patients who received neck dissection had negative pathologic results. On univariate analysis, initial nodal size > 2 cm, a less-than-complete response at the primary site, post-radiotherapy nodal size > 1.5 cm, and post-radiotherapy nodal necrosis were associated with RC. On multivariate analysis, less-than-complete primary site response and post-radiotherapy nodal necrosis were identified as independent prognostic factors for RC.</p> <p>Conclusions</p> <p>The neck failure rate after definitive radiochemotherapy without planned neck dissection was 22%. Two-thirds of these were successfully salvaged with neck dissection and the ultimate neck control rate was 92%. Our results suggest that planned neck dissection might not be necessary in patients with complete response of primary site, no evidence of residual lesion > 1.5 cm, or no necrotic lymph nodes at the 1-2 months follow-up evaluation after radiotherapy.</p

Idiopathic severe hypermagnesemia in an extremely low birth weight infant on the first day of life

A preterm female infant born at 27 weeks of gestation with a birth weight of 990 g developed acute hypotonia, apnea, hypotension and bradycardia mimicking septic shock syndrome at 14h after birth. Laboratory tests indicated a severe hypermagnesemia of 45 mg/dL. The renal function, complete blood count and maternal blood concentrations of magnesium were normal, and the blood cultures were negative. The patient recovered with treatment including exchange transfusion. However, the etiology of the severe hypermagnesemia remains unknown

Stemness Evaluation of Mesenchymal Stem Cells from Placentas According to Developmental Stage: Comparison to Those from Adult Bone Marrow

This study was done to evaluate the stemness of human mesenchymal stem cells (hMSCs) derived from placenta according to the development stage and to compare the results to those from adult bone marrow (BM). Based on the source of hMSCs, three groups were defined: group I included term placentas, group II included first-trimester placentas, and group III included adult BM samples. The stemness was evaluated by the proliferation capacity, immunophenotypic expression, mesoderm differentiation, expression of pluripotency markers including telomerase activity. The cumulative population doubling, indicating the proliferation capacity, was significantly higher in group II (P<0.001, 31.7±5.8 vs. 15.7±6.2 with group I, 9.2±4.9 with group III). The pattern of immunophenotypic expression and mesoderm differentiation into adipocytes and osteocytes were similar in all three groups. The expression of pluripotency markers including ALP, SSEA-4, TRA-1-60, TRA-1-81, Oct-4, and telomerase were strongly positive in group II, but very faint positive in the other groups. In conclusions, hMSCs from placentas have different characteristics according to their developmental stage and express mesenchymal stemness potentials similar to those from adult human BMs

Neuroprotective effects of mild hypoxia in organotypic hippocampal slice cultures

PurposeThe aim of this study was to investigate the potential effects of mild hypoxia in the mature and immature brain.MethodsWe prepared organotypic slice cultures of the hippocampus and used hippocampal tissue cultures at 7 and 14 days in vitro (DIV) to represent the immature and mature brain, respectively. Tissue cultures were exposed to 10% oxygen for 60 minutes. Twenty-four hours after this hypoxic insult, propidium iodide fluorescence images were obtained, and the damaged areas in the cornu ammonis 1 (CA1), CA3, and dentate gyrus (DG) were measured using image analysis.ResultsIn the 7-DIV group compared to control tissue, hypoxia-exposed tissue showed decreased damage in two regions (CA1: 5.59%±2.99% vs. 4.80%±1.37%, P=0.900; DG: 33.88%±12.53% vs. 15.98%±2.37%, P=0.166), but this decrease was not statistically significant. In the 14-DIV group, hypoxia-exposed tissue showed decreased damage compared to control tissues; this decrease was not significant in the CA3 (24.51%±6.05% vs. 18.31%±3.28%, P=0.373) or DG (15.72%±3.47% vs. 9.91%±2.11%, P=0.134), but was significant in the CA1 (50.91%±5.90% vs. 32.30%±3.34%, P=0.004).ConclusionAlthough only CA1 tissues cultured for 14 DIV showed significantly less damage after exposure to hypoxia, the other tissues examined in this study showed a tendency towards less damage after hypoxic exposure. Therefore, mild hypoxia might play a protective role in the brain

The efficacy of tenofovir-based therapy in patients showing suboptimal response to entecavir-adefovir combination therapy

Background/Aims: Before tenofovir (TDF) become available in South Korea, combination therapy with entecavir (ETV) and adefovir (ADV) was the most potent regimen for chronic hepatitis B (CHB) patients who fail to respond to rescue therapy for drug resistance. We analyzed the efficacy of ETV-ADV combination therapy and investigated the clinical and clonal results of TDF-based rescue therapy in CHB patients refractory to this combination. Methods: We retrospectively reviewed the medical records of CHB patients treated for up to 3 years with ETV-ADV combination therapy as a rescue therapy for drug resistance. In cases refractory to this combination, clinical and clonal analyses were performed for TDF-based rescue therapy. Results: The analysis was performed on 48 patients. Twelve patients achieved a virological response (VR) within 3 years. A VR was subsequently achieved in nine of the ten patients without a VR who switched to TDF monotherapy. A VR was also achieved in six of the seven patients who switched to lamivudine-TDF combination therapy, and in two of the two patients who switched to ETV-TDF combination therapy. In an in vitro susceptibility test, viral replication was detected with TDF monotherapy but not with ETV-TDF combination therapy. Conclusions: The efficacy of ETV-ADV combination therapy was insufficient in CHB patients who were refractory to rescue therapy. A more potent regimen such as ETV-TDF combination therapy may be considered in such refractory cases

Effect of unsupervised Kinect-based mixed reality fitness programs on health-related fitness in men during COVID-19 pandemic: randomized controlled study

This study aimed to investigate the effect of Kinect-based mixed reality (KMR) exercise and unsupervised individual exercise on health-related fitness. A total of 27 participants underwent cardiorespiratory fitness tests for the inclusion criteria and were randomly assigned to three groups: a KMR group (KMRG), an unsupervised individual group (UIG), or a control group (CG). Pre and post-tests were conducted to measure Maximum oxygen uptake (VO₂max), body composition, upper and lower-body (LB) muscle strength, and endurance. KMRG and UIG attended exercise sessions 3 days per week for 8 weeks. KMRG used the KMR device and UIG used an instructive banner for exercise. All groups maintained their daily routines and submitted diet records every 4 weeks. Results showed that VO₂max, upper-body muscle endurance, and LB muscle endurance of knee extension was increased in KMRG and UIG. LB muscle strength in knee flexion was increased in UIG and LB muscle endurance in knee flexion was increased in KMRG. VO₂max, LB muscle strength, and LB muscle endurance were greater in KMRG than in CG. LB muscle strength in knee flexion was greater in KMRG than in UIG. Body fat was increased and skeletal muscle mass was decreased in CG. KMR exercise showed better performance than unsupervised individual (UI) exercise, and the exercise program was effective in both KMR and UI environments. These findings contribute to the growing evidence supporting the use of technology-based exercise interventions as a potential strategy to enhance health-related fitness