Personaneinsatz- und Tourenplanung für Mitarbeiter mit Mehrfachqualifikationen

In workforce routing and scheduling there are many applications in which differently skilled workers must perform jobs that occur at different locations, where each job requires a particular combination of skills. In many such applications, a group of workers must be sent out to provide all skills required by a job. Examples are found in maintenance operations, the construction sector, health care operations, or consultancies. In this thesis, we analyze the combined problem of composing worker groups (teams) and routing these teams under goals expressing service-, fairness-, and cost-objectives. We develop mathematical optimization models and heuristic solution methods for an integrated solution and a sequential solution of the teaming- and routing-subproblems . Computational experiments are conducted to identify the tradeoff of better solution quality and computational effort

Whole blood Fe isotopic signature in a sub-Saharan African population

The Fe isotopic composition of an individual's whole blood has recently been shown to be an interesting clinical indicator of Fe status. The present study aimed to evaluate the influence of several endemic characteristics of a representative population of the South Kivu province, an Fe-rich volcanic African region, on the whole blood Fe isotopic composition. Both diabetes mellitus and the ferroportin Q248H mutation are very common in Africa and are strongly associated with impairments in Fe metabolism. Fe isotopic analysis of whole blood samples was carried out using multi-collector inductively coupled plasma-mass spectrometry (after chromatographic isolation of the target element). Forty-two male subjects (between 48 and 59 years old) living in Bukavu (South Kivu) were enrolled in this study. Among the selected population, wild-type subjects and subjects presenting the ferroportin Q248H mutation (heterozygotes and homozygotes) were included. Within each group, diabetic and non-diabetic patients were considered. The whole blood delta Fe-56 value ranged from -3.09% to -2.41%. The delta Fe-56 value shows a significant negative correlation with the ferritin concentration. No correlation could be established between the whole blood delta Fe-56 value and the transferrin concentration, transferrin saturation or serum Fe concentration. The ferroportin Q248H mutation did not seem to have affected the whole blood Fe isotopic signature. The whole blood delta Fe-56 values were significantly higher in diabetic subjects than in non-diabetic subjects and showed a significant negative correlation with body mass index (BMI) values

Iron isotopic analysis of finger-prick and venous blood by multi-collector inductively coupled plasma-mass spectrometry after volumetric absorptive microsampling

High-precision isotopic analysis of Fe in blood is currently assessed as a complementary approach to achieve a better understanding of human Fe metabolism and for diagnosis of diseases. Volumetric absorptive microsampling (VAMS) is a recently introduced technique that allows the straightforward collection of a well-defined volume of blood by dipping an absorbent polymeric tip into it. In this work, the use of VAMS was evaluated for high-precision isotopic analysis of whole blood Fe by multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS). Fe concentrations in whole blood sampled using VAMS were determined by single-collector sector-field ICP-MS. A variety of solvents were evaluated for extraction of Fe from the VAMS-device (Mitra T). Fe was quantitatively extracted from the absorbent using 1 mL of Milli-Q water. The extracted material was subsequently subjected to acid digestion and to a miniaturized chromatographic procedure for isolation of Fe from the blood matrix. The Fe isotopic compositions and concentrations of paired finger-prick and venous blood samples collected at the same time from six individuals were compared. No significant differences were found between the two blood types. The proposed methodology significantly increases the sample throughput and facilitates sample acquisition for Fe isotopic analysis in clinical applications

High-precision Fe isotopic analysis of whole blood for biomedical purposes without prior isolation of the target element

Recently, it has been documented that Fe isotopic analysis of whole blood and serum by means of multi-collector ICP-mass spectrometry (MC-ICP-MS) provides promising results in a biomedical context and, thus, there is a demand for simple, fast and reliable methodologies, providing a high sample throughput. In this work, the possibility of Fe isotopic analysis by MC-ICP-MS directly in acid-digested whole blood and, thus, without prior Fe isolation was evaluated. The influence of the main mineral matrix elements and the effect of potentially remaining organic compounds were first systematically evaluated using synthetic solutions. The Fe isotopic composition was biased low in the presence of matrix elements such as Na and K, while it was biased high for glucose concentrations >= 1% (w/v). Nevertheless, after dilution of the whole blood sample digest to 0.75-1.5 mg L-1 of Fe, followed by adequate correction for instrumental mass discrimination using a combination of internal (with admixed Ni) and external correction, MC-ICP-MS isotope ratio measurements provided accurate and precise results. For actual samples, the Fe isotopic data thus obtained agree well with those obtained using the reference procedure, based on prior chromatographic isolation of Fe from acid-digested blood

Isotopic analysis of Cu in blood serum by multi-collector ICP-mass spectrometry : a new approach for the diagnosis and prognosis of liver cirrhosis?

The isotopic composition of blood serum Cu has been investigated as a potential parameter for the diagnosis and prognosis of liver cirrhosis. Serum samples from supposedly healthy women (reference population) and from a group of female patients suffering from liver cirrhosis of different etiologies were analysed. The procedure for isolation of serum Cu and the measurement protocol for its isotopic analysis by multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) were evaluated. Significant differences in the isotopic composition of Cu were observed between the reference population and the patients. A wide spread in delta Cu-65 was observed within the cirrhosis population and delta Cu-65 seems to be linked to the severity of the disease. Patients with end-stage liver disease showed a significantly lighter serum Cu isotopic composition. Many clinical parameters used for the diagnosis and monitoring of liver diseases, i.e. the levels of aspartate aminotransferase, De Ritis ratio, prothrombin and international normalized ratio, albumin, bilirubin, Na and C-reactive protein, correlate well with the delta Cu-65 values, as did the ceruloplasmin level and the ceruloplasmin/Cu concentration ratio. The isotopic composition of serum Cu appears to reveal the synthetic and hepatocellular function of the liver synergistically with inflammation and fluid retention in the cohort studied. A relevant relationship was also observed between delta Cu-65 and scores of mortality risk, such as the Model for End-stage Liver Disease (MELD) and MELD-Na. Thus, the isotopic composition of serum Cu shows potential as a new approach for the prognosis of liver disease, and although further investigation is required, for evaluation of the mortality risk in end-stage liver disease and prioritization of liver transplant

Iron isotopic composition of blood serum in anemia of chronic kidney disease

Chronic kidney disease (CKD) is a general term for disorders that affect the structure and function of the kidneys. Iron deficiency (ID) and anemia occur in the vast majority of CKD patients, most of whom are elderly. However, establishing the cause of anemia in CKD, and therefore making an informed decision concerning the corresponding therapeutic treatment, is still a challenge. High-precision Fe isotopic analysis of blood serum samples of CKD patients with and without ID/anemia was performed via multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) for such a purpose. Patients with CKD and/or iron disorders showed a heavier serum Fe isotopic composition than controls. Many clinical parameters used for the diagnosis and follow-up of anemia correlated significantly with the serum Fe isotopic composition. In contrast, no relation was observed between the serum Fe isotopic composition and the estimated glomerular filtration rate as a measure of kidney function. Among the CKD patients, the serum Fe isotopic composition was substantially heavier in the occurrence of ID anemia, while erythropoietin-related anemia did not exert this effect. The Fe isotopic composition can thus be useful for distinguishing these different types of anemias in CKD patients, i.e. ID anemia vs. erythropoietin-related anemia

High-precision isotopic analysis of serum and whole blood Cu, Fe and Zn to assess possible homeostasis alterations due to bariatric surgery

Bariatric surgery is an effective procedure to achieve weight loss in obese patients. However, homeostasis of essential metals may be disrupted as the main absorption site is bypassed. In this study, we determined Cu, Fe and Zn isotopic compositions in paired serum and whole blood samples of patients who underwent Roux-en-Y gastric bypass (RYGB) surgery for evaluation of longitudinal changes and their potential relation to mineral element concentrations and relevant clinical parameters used for monitoring the patient's condition. Samples from eight patients were collected pre-surgery and at 3, 6 and 12 months post-surgery. Multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) was used for high-precision isotope ratio measurements. Alterations in metal homeostasis related to bariatric surgery were reflected in the serum and whole blood Cu, Fe and Zn isotopic compositions. The serum and whole blood Cu became isotopically lighter (lower delta Cu-65 values) after bariatric surgery, reaching statistical significance at 6 months post-surgery (p < 0.05). The difference between the serum and the whole blood Zn isotopic composition increased after surgery, reaching significance from 6 months post-surgery onwards (p < 0.05). Those changes in Cu, Fe and Zn isotopic compositions were not accompanied by similar changes in their respective concentrations, making isotopic analysis more sensitive to physiological changes than elemental content. Furthermore, the Zn isotopic composition correlates with blood glycaemic and lipid parameters, while the Fe isotopic composition correlates with glycaemic parameters

Natural Fe isotope fractionation in an intestinal Caco-2 cell line model

In this work, Fe isotopic analysis of samples obtained from an in vitro intestinal model was performed via multi-collector ICP-mass spectrometry (MC-ICP-MS) to evaluate the isotope fractionation accompanying Fe uptake and transport mechanisms at a cellular level. The Caco-2 cell line has been used, after cell differentiation, as an enterocyte model and a bi-cameral experimental setup has been developed and optimized for stimulating intracellular Fe fluxes. An Fe : ascorbic acid mixture with a molar ratio of 1 : 5 was used as a source of non-heme bioavailable Fe. Good experimental repeatability and reproducibility were attained with low blank contribution levels, allowing precise and reliable Fe isotope ratio results. Both Fe absorption and transport processes were accompanied by Fe isotope fractionation in favor of the lighter isotopes. After 3 hours of exposure, the isotopic composition of the apical solution and the cells did not significantly differ from that of the original solution added to the cells. After 24 hours of exposure, the trend observed was towards a light Fe isotopic composition in the cells, whereas the apical solutions were enriched in the heavier isotopes. These results were in good agreement with previous in vivo and ex vivo findings. An overall increase in delta Fe values of the cell layers exposed to Fe treatment relative to the corresponding values for the untreated cells also seems to support the assumption of a preferential accumulation of heavy isotopes in enterocyte ferritin. The consistency of the results obtained supports the usefulness of in vitro cell culture models as an interesting complementary tool for studying Fe metabolic pathways at the intestinal level