A Vehicle Routing Problem with Time Windows and Workload Balancing for COVID-19 Testers: A Case Study.

Due to the COVID-19 pandemic, laboratories have faced unprecedented demand for in-home delivery test services. This drastic demand increase requires a rapid reaction from laboratories to manage their testers in order to respond to the high demand volume and avoid unnecessary costs. This study provides an optimization model based on the vehicle routing problem with time windows by considering the testers' workload balancing to improve laboratories' assignment and routing policies. A medical lab that has faced this situation for its in-home test services is taken as a real-world case in the current study. A mixed-integer programming model is solved for small instances using the CPLEX solver, and an adaptive large neighborhood search algorithm is implemented for large instances. Ultimately, the obtained solutions are compared to the real-world implementation of the lab on a dataset of six consecutive days, and the results are further discussed.

Effects of ABO incompatibility in allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: The impact of ABO mismatch on outcomes following allo-HSCT remains controversial. In this study, our aim is to define the effect of ABO mismatch on post-transplant outcomes, engraftment kinetics and complications in a large cohort. PATIENTS AND METHODS: We retrospectively identified 1000 patients who underwent allo-HSCT from either bone marrow or peripheral blood stem cells at our center between 1988 and 2016. P<0.05 was considered statistically significant. RESULTS: Five hundred and ninety (59%) patient-donor pairs were ABO matched, 164 (16.4%) were ABO major mismatched (MM), 191 (19.1%) were ABO minor MM, and 55 (5.5%) were ABO bi-directionally MM. ABO matched pairs were more common in transplants from related donors (P<0.001) and using bone marrow as a stem cell source (P<0.001). In minor ABO MM transplantations, mild delayed hemolytic reaction occurred more frequently compared to major and bidirectional ABO MM transplantations (47% vs 35% and 18%, P<0.001). Neutrophil engraftment was slightly delayed in ABO MM patient-donor pairs when compared ABO matched donor pairs according to median engraftment time in all group (167/410, 41% vs 204/590, 35%, P=0.046). Pure red cell aplasia was diagnosed in 6 patients (1%). Higher risk of death was shown in ABO MM transplants compared to ABO matched transplants in overall survival (OS) analysis (HR:1.201, 95% CI:1.004-1.437, P=0.045). The non-relapse mortality (P=0.546) and cumulative incidences of acute graft versus host disease (aGVHD) and chronic (c) GVHD were comparable between ABO MM and ABO matched patient-donor pairs (for aGVHD, P=0.235; for cGVHD, P=0.137). CONCLUSION: ABO MM transplants were associated with decreased OS and slightly delayed neutrophil engraftment. NRM and the risk of GVHD were not related to ABO incompatibility.

Haploidentical stem cell transplantation: T cell depleted and repleted.

Allogeneic hematopoietic stem cell transplantation (AHSCT), is a curative treatment option for many hematological diseases. Donor availability is the major limiting factor in the transplantation setting. More than half of the patients do not have a HLA fully matched related/unrelated donor but almost all patients have an haploidentical donor. Haploidentical transplantion can be performed either as T cell depleted or repleted. Despite the promising results in T cell depletion methods, expensive T cell selection and the necessity for experienced staff seem to be the limiting factors. However, a T cell repleted haploidentical stem cell transplantation strategy is simple, cheap and has been preferred by different transplant centers worldwide.

Comparison of performance and abnormal cell flagging of two automated hematology analyzers: Sysmex XN 3000 and Beckman Coulter DxH 800.

INTRODUCTION: The purpose was to evaluate the analytical performances of Sysmex XN 3000 and UniCel DxH 800 comparing the obtained results with manual counting and between each other. Also flagging capabilities of abnormal cells were compared for both analyzers. METHODS: Two thousand one hundred and forty-two whole-blood samples were analyzed for evaluation. The samples flagged due to blast, atypical lymphocyte (AL), immature granulocyte (IG), or nucleated red blood cells (NRBC) were microscopically reviewed (n=102). RESULTS: The within-run and between-day coefficient of variations (CV%) of XN 3000 for hemoglobin, RBC, MCV, WBC, and platelets were lower than 5% and for WBC differentials lower than 10% except monocytes which was 15.6% at low level. The precision results of DxH 800 were also lower than 5.0% except platelets (9.5%) and monocytes (45%) at low level. The comparison of analyzers revealed good agreement (R>.86), except monocytes and basophils. The flagging sensitivities of XN 3000 were higher for IGs, blasts, and ALs than those of DxH 800 and almost similar for NRBC. CONCLUSION: The XN 3000 and DxH 800 are accurate, highly precise systems and can be used effectively in high-volume laboratories. The flagging sensitivity of XN 3000 was higher in detecting blasts, IGs, and ALs than that of DxH 800. The detection of abnormal cells with high sensitivity may improve laboratory workflow with a reduced slide review and accelerated turnaround time.

Extracorporeal photochemotherapy in mycosis fungoides.

OBJECTIVES: Extracorporeal photo-chemotherapy (ECP, photopheresis) is an approved treatment modality for mycosis fungoides (MF). Our aim is to present our ECP data for MF. METHODS: We retrospectively evaluated 50 MF patients who received ECP for clinical activity, toxicity, and response and outcome rates, and we compared these with combination therapies. RESULTS: The overall response rate (ORR) was 42% (21/50), while the median time to response was 11months (range, 3-48months). Ten of the responders (48%) had 3 or more treatment lines prior to ECP. Eight patients (16%) had adverse events related to ECP. The overall survival (OS) of 50 patients was 72months (range, 3-211). There was no statistically significant difference in the OS in early-stage vs late-stage patients (77 vs 69months, P=0.077). The stage 3 and 4 patients received an average of 31 cycles compared to 55 cycles in stage 1 and 2 patients (P=0.006). The increased extent of ECP was not correlated with the response. Combined treatment with ECP significantly improved the OS (84months vs 62months, P=0.005). DISCUSSION: A low frequency of side effects and improved OS observed in combination therapy makes ECP a favorable option for treating MF.

A retrospective analysis of patients treated for gestational trophoblastic diseases: a 4-year experience of a tertiary hospital.

AIM: To study incidence, clinical outcome, and follow-up data of the gestational trophoblastic disease (GTD) in patients diagnosed in the present Department. MATERIALS AND METHODS: This study included the authors' retrospective clinical records regarding the cases of GTD which were diagnosed and followed up between January 2011 and January 2015. Patients' age, gravidity and parity, obstetric history, subgroup of GTD, gestational weeks, management results, and pre-post treatment ß-hCG levels was investigated and an incidence study was constituted. RESULTS: Total of 56 GTD cases were hospitalized and clinical records of 16,840 normal spontaneous deliveries were evaluated during the study period. The incidence of GTD was 3.3/1,000 cases. After histopathological examination, nine of 47 cases were partial molar pregnancy, whereas 38 cases were complete moles. There were no choriocarcinoma and invasive moles. All cases were treated with vacuum curettage without complication. CONCLUSION: The GTD incidence in this clinic is high with a rate of 3.3/1,000 per pregnancy compared to Turkish literature. High birth rates of our population may play a role in high incidence results. Further investigation in this field is essential.

Late coronary stent dislodgement following coronary artery stenting.

Recently, coronary artery stenting has been successful when used as an intervention for percutaneous coronary artery disease. However, the procedure may frequently produce complications. Although rare, stent dislodgement is one such complication, which may result in serious problems including coronary artery dissection, myocardial infarction, peripheral embolisation and death. Stent dislodgement is known to be an early complication of the coronary artery stenting procedure. In this case report, we present a 53-year-old male with late coronary stent dislodgement. To the best of our knowledge, no such case has been addressed in the literature to date.

Spatial analysis of perinatal mortality rates with geographic information systems in Kocaeli, Turkey.

OBJECTIVES: To determine the spatial patterns of perinatal mortality in Kocaeli, Turkey using geographic information systems (GIS); to examine whether regional differences exist for the period selected; and whether these differences are linked to regional risk factors. STUDY DESIGN: Ecological research. METHODS: Data were obtained from the linked birth-death records data registry maintained by Kocaeli Provincial Health Directorate. Mortality data are added to the geodatabase on a monthly basis. Spatial patterns of mortality rates were determined with GIS by mapping the case differences in the districts, and spatial autocorrelation was used to examine the spatial pattern of mortality rates in the region. RESULTS: Various risk factors contributing to spatial variation of perinatal mortality were revealed in the region. Districts with high mortality rates were shown to be sensitive to these risk factors. The results of this study confirm the direct link between perinatal mortality and poor environmental conditions in the study region. The analyses applied in the study showed that some complex demographic and socio-economic factors should be associated with perinatal mortality rates to identify the geographic patterns of mortality. CONCLUSIONS: Implementation of spatial tools within GIS for mortality data showed the efficiency of GIS in perinatal mortality surveillance. This study also demonstrated the capability and utility of GIS to clarify the geographical distribution of perinatal mortality rates in the study area.

ABO and Rh blood groups frequency in women with HER2 positive breast cancer.

PURPOSE: The role of genetic factors in the development of cancer is widely accepted. Data on the role of ABO blood group and Rh factor in breast cancer is inconclusive. The aim of this study was to investigate the presence of a possible association between HER2 (+) breast cancer in Turkish women and ABO blood groups and Rh factor. METHODS: In 294 female patients with HER2 (+) breast cancer, ABO blood groups and Rh factor were examined. The relationship of blood groups with age, menopausal status, and family history of cancer, estrogen receptor (ER), progesterone receptor (PR) and HER2 status of these patients was evaluated. Blood groups distribution of 22,821 healthy blood donors was also assessed and compared with the patients' blood groups distribution. RESULTS: The median patient age was 47 years (range 20-80) and 56% of the patients were premenopausal. ER and PR were positive in 50 and 60% of the patients, respectively. Overall, the ABO blood group distribution of the 294 HER2 (+) breast cancer patients was similar to that of the healthy blood donors (p=0.36). Likewise there was no correlation between blood type and ER, PR and menopausal status. Rh (-) patients had more frequent family cancer history and this difference was significant for patients with blood group B Rh (-) and O Rh (-) (p = 0.04). CONCLUSION: In the present study we didn't find any relationship between HER2 status and ABO blood group and Rh factor. However, further studies with larger number of patients are needed to establish the role (if any) of blood groups in patients with breast cancer.

Comparing deep anterior lamellar keratoplasty and automated lamellar therapeutic keratoplasty in patients with keratoconus.

PURPOSE: We compared outcomes of deep anterior lamellar keratoplasty (DALK) and automated lamellar therapeutic keratoplasty (ALTK) in patients with keratoconus. METHODS: Seventy eyes with keratoconus that underwent corneal transplantation using either DALK (n = 40) or ALTK (n = 30) were included in this retrospective study. DALK was performed with Anwar's big-bubble technique and ALTK using an ALTK system. Best-corrected visual acuity (BCVA), refractive results, and complications were analyzed. RESULTS: Mean follow-up in the DALK (16.68 ± 3.36 months) and ALTK (15.27 ± 2.50 months) groups were similar (p = 0.058). Mean final BCVA of patients in the DALK group was 0.31 ± 0.14 logarithm of the minimum angle of resolution (logMAR) and in the ALTK group 0.34 ± 0.15 logMAR, (p = 0.492). Corresponding figures for final postoperative spherical equivalents were -3.45 ± 0.77 D and -4.19 ± 0.99 D, respectively (p = 0.001). Final postoperative degree of astigmatism was similar in the two groups: DALK -4.28 ± 0.66 D; ALTK -4.50 ± 1.05 D (p = 0.307). CONCLUSION: Final visual acuity outcomes were comparable for the DALK and ALTK groups. Thus, ALTK seem to be as efficacious as DALK for surgical treatment of keratoconus.

Incremental Multi-Scale Search Algorithm for Dynamic Path Planning With Low Worst-Case Complexity.

Path-planning (equivalently, path-finding) problems are fundamental in many applications, such as transportation, VLSI design, robot navigation, and many more. In this paper, we consider dynamic shortest path-planning problems on a graph with a single endpoint pair and with potentially changing edge weights over time. Several algorithms exist in the literature that solve this problem, notably among them the Lifelong Planning algorithm. The algorithm is an incremental search algorithm that replans the path when there are changes in the environment. In numerical experiments, however, it was observed that the performance of is sensitive in the number of vertex expansions required to update the graph when an edge weight value changes or when a vertex is added or deleted. Although, in most cases, the classical requires a relatively small number of updates, in some other cases the amount of work required by the to find the optimal path can be overwhelming. To address this issue, in this paper, we propose an extension of the baseline algorithm, by making efficient use of a multiscale representation of the environment. This multiscale representation allows one to quickly localize the changed edges, and subsequently update the priority queue efficiently. This incremental multiscale ( for short) algorithm leads to an improvement both in terms of robustness and computational complexity-in the worst case-when compared to the classical . Numerical experiments validate the aforementioned claims.

Mobilization of PBSCs with chemotherapy and recombinant human G-CSF: a randomized evaluation of early vs late administration of recombinant human G-CSF.

The optimal timing for recombinant human (rh)G-CSF administration after chemotherapy for PBSC mobilization has not yet been determined. In this study, we compared two different time schedules of rhG-CSF; 4th (early) vs 7th day (late), in 48 consecutive patients with multiple myeloma and lymphoma undergoing PBSC mobilization with CE (CY 4 g/m(2) on day 1 and etoposide 200 mg/m(2) on days 1-3). The rhG-CSF dose was 10 microg/kg/day for all patients. Both groups were comparable in terms of sex, age and number of previously given different chemotherapy regimens. Duration of neutropenia, CD34(+) cell count on the first day of apheresis and numbers of aphereses were not statistically different between the two arms. However, the number of doses of rhG-CSF up to the first cycle of apheresis procedures was significantly lower in the late group than in the early group (P=0.005). The median number of total CD34(+) cells collected was 10.54 x 10(6)/kg (range 0.11-37.27) in the early group and 10.81 x 10(6)/kg (range 0.17-49.83) in the late group of rhG-CSF (P=0.781). We conclude that PBSC mobilization after late use of rhG-CSF is an effective approach and therefore, in routine clinical practice, late rhG-CSF may be used for PBSC collections after chemotherapy-based mobilization regimens in this cost-conscious era.

Differential in vitro inhibitory effects of anticancer drugs on tumor-associated carbonic anhydrase isozymes CA IX and CA XII.

Carbonic anhydrase IX (CA IX) and, to a lesser extent, carbonic anhydrase XII (CA XII) are highly overexpressed in hypoxic tumors. In this study, the inhibitory effects of 11 different anticancer drugs including paclitaxel, amethopterin, etoposide, irinotecan, gemcitabine, 5-fluorouracil, oxaliplatin, epirubicin, cisplatin and carboplatin on the tumor-associated carbonic anhydrase isozymes CA IX and CA XII and cytosolic carbonic anhydrases I and II have been investigated. SX.18MV-R Applied Photophysics stopped-flow instrument was used for measuring the initial velocities for the CO2 hydration reaction catalyzed by different CA isozymes, by following the change in the absorbance of a pH indicator. CA IX and CA XII were the most affected by carboplatin and cisplatin amongst the panel of anticancer drugs. Moreover, the cytosolic carbonic anhydrases I and II can also be affected. Consequently, CA IX and CA XII are interesting targets for anticancer drug development, although more selective and powerful CA inhibitors could prove useful for elucidating the role of the protein in hypoxic cancers, for controlling the pH imbalance in tumor cells and for developing diagnostic or therapeutic applications for the management of hypoxic tumors, generally unresponsive to classical chemo- and radiotherapy.

Whole blood donor deferral rate and characteristics of the Turkish population.

Whole blood (WB) donors are deferred for several reasons, either permanently or temporarily. In this retrospective study, we quantified the rate of and reasons for donor deferral among Turkish donors. Computer records of the last 5 years were analysed to quantify the deferral rate and reasons. Deferrals were categorized as temporary short-term (1-56 days), long-term (57-365 days) and multiple years or permanent (more than 365 days). Deferred donors were also analysed according to gender, age and education level. A total of 95 317 persons were admitted for WB donation: 89.1% of them were male donors and 59.9% were in the 30 to 49-year old age category. Rates of deferral for temporary short-term, long-term, permanent or for unknown reasons were 66, 22.5, 10 and 1.5% respectively. Female donors were deferred more frequently than male donors (25.8 vs. 13.3%, P 0.05). The main reason for deferral was common cold and/or sore throat or elevated temperature (20.4%) in male donors and low haemoglobin (51.6%) in female donors. Although the three uppermost reasons for deferral in women were identical for all age categories, these varied in the male group (high-risk sex partner for the younger group vs. hypertension and low haemoglobin for the older group). Although permanent and temporary deferral rates are similar between the Turkish population and western countries, leading causes vary widely.

The effects of nonylphenol and octylphenol on embryonic development of sea urchin (Paracentrotus lividus).

In this study, embryotoxic and genotoxic effects of nonylphenol (NP) and octylphenol (OP), which are the derivates of alkylphenol (APs), were evaluated using the gametes and embryos of the sea urchin Paracentrotus lividus. The sperm and eggs of sea urchins were exposed to increasing concentrations of NP (0.937-18.74 microg/L) and OP (5-160 microg/L) under static conditions. The endpoints were sperm fertilization success, quantitative and morphologic changes in mitotic activity, larval malformations, developmental arrest, and embryonic/larval mortality. A dose-response-related reduction (approximately 20%) was observed in fertilization success and significant increases in the number of larvae with skeleton malformations at the pluteus stage of the contaminated sperms. The spermiotoxic and embryotoxic concentrations were determined as 0.937 microg/L for NP and 4.685 microg/L for OP for this species. The embryotoxicity of NP and OP is concentration dependent, and significant growth reduction at the early life stages and an increase in larval malformations as skeleton deformities at the pluteus stage were observed. Cytogenetic analysis of embryos showed a decreasing curve in mitotic indexes (number of mitosis per embryo) with increasing concentrations of NP and OP. It can be concluded that NP and OP adversely affect the reproduction and embryonic developmental stages of the P. lividus and this is of great ecological importance because of the hazard at the population level.

Embryotoxic effects of nonylphenol and octylphenol in sea urchin Arbacia lixula.

Nonylphenol (NP) and octylphenol (OP), both of which are biodegradation products of alkylphenols, are widely used in industrial applications and in some domestic products. These chemicals are found widely in surface water and aquatic sediments. We have carried out a comparative embryotoxicity analysis of the effects of increasing concentrations of NP (seven concentrations ranging from 0.937 to 18.74 microg/l) and OP (six concentrations ranging from 5 to 160 microg/l) on embryos of the sea urchin Arbacia lixula. The indicators evaluated were larval malformations, developmental arrest and embryonic/larval mortality. The results revealed that low concentrations of these chemicals (NP, OP) generally caused malformations in the skeletal system. High concentrations (18.74 microg NP/l, 160 microg OP/l) were found to inhibit the growth of embryos in the early life stages by preventing mitosis. We conclude that NP and OP present a major risk to the normal development of A. lixula at the low concentrations that have been recorded in the environment. These chemicals are therefore most likely to represent an ecological hazard at the population level given the cumulative effects of other environmental pollutants.

Spatio-temporal genetic variation in populations of wild emmer wheat, Triticum turgidum ssp. dicoccoides, as revealed by AFLP analysis.

Genetic structure of natural populations of wild crop relatives has been the subject of many studies. Yet, most of them focused on the assessment of spatial genetic diversity, while information on long-term variation, affected by yearly changes, has been considered only in few cases. The present study aimed therefore, to estimate the spatio-temporal genetic variation in populations of wild emmer wheat, the progenitor of domesticated wheat, and to assess the contribution of spatial versus temporal factors to the maintenance of genetic variation in a population. Single spikes were collected in the years 1988 and 2002 from plants that grew in the same sampling points, from six different habitats in the Ammiad conservation site, Eastern Galilee, Israel. Seeds were planted in a nursery and DNA was extracted from each plant and analyzed by the AFLP method. Fourteen primer combinations yielded 1,545 bands of which 50.0 and 48.8% were polymorphic in the years 1988 and 2002, respectively. Genetic diversity was much larger within populations than between populations and the temporal genetic diversity was considerably smaller than the spatial one. Nevertheless, population genetic structure may vary to some degree in different years, mainly due to fluctuations in population size because of yearly rainfall variations. This may lead to predominance of different genotypes in different years. Clustering the plants by their genetic distances grouped them according to their habitats, indicating the existence of genotype-environment affinities. The significance of the results in relation to factors affecting the maintenance of polymorphism in natural populations is discussed.

Amphenicol and macrolide derived antibiotics inhibit paraoxonase enzyme activity in human serum and human hepatoma cells (HepG2) in vitro.

Human serum paraoxonase (hPON1) was separately purified by ammonium sulfate precipitation and hydrophobic interaction chromatography. The in vitro effects of commonly used antibiotics, namely clarithromycin and chloramphenicol, on purified human serum paraoxonase enzyme activity (serum hPON1) and human hepatoma (HepG2) cell paraoxonase enzyme activity (liver hPON1) were determined. Serum hPON1 and liver hPON1 were determined using paraoxon as a substrate and IC(50) values of these drugs exhibiting inhibition effects were found from graphs of hydratase activity (%) by plotting concentration of the drugs. We determined that chloramphenicol and clarithromycin were effective inhibitors of serum hPON1.