103 research outputs found
Workforce Rostering for Tomorrow's Industry: The Workforce Scheduling Dilemma in Decentrally Controlled Production Systems
The workforce rostering for tomorrow’s industry needs to be reconsidered. The development of new types of production control mechanisms, like decentralized production control, impacts the effectivity and efficiency of workforce rostering methods, too. Simultaneously, social trends, like the growing demand of flexible working time models and labor shortages, take their influence on the rostering process. We are facing these requirements by developing a new rostering method which is appropriate for decentrally controlled production systems, the consideration of individual preferred working times independent of rigid shift systems and the simultaneous targeting of production-related performance variables. Therefore, we apply a simulation-based optimization approach which is based on a genetic algorithm
Choosy and Picky: Configuration of Language Product Lines
Although most programming languages naturally share several language features, they are typically implemented as a monolithic product. Language features cannot be plugged and unplugged from a language and reused in another language. Some modular approaches to language construction do exist but composing language features requires a deep understanding of its implementation hampering their use. The choose and pick approach from software product lines provides an easy way to compose a language out of a set of language features. However, current approaches to language product lines are not sufficient enough to cope with the complexity and evolution of real world programming languages. In this work, we propose a general light-weight bottom-up approach to automatically extract a feature model from a set of tagged language components. We applied this approach to the Neverlang language development framework and developed the AiDE tool to guide language developers towards a valid language composition. The approach has been evaluated on a decomposed version of Javascript to highlight the benefits of such a language product line
Automatisierte Generierung und Simulation von Hyper-Heuristiken für stochastische Multi-Modus-Multi-Projekt-ressourcenbeschränkte Projekt- und Systemplanungsprobleme mit Umrüstzeiten
A simulation framework is presented which covers both generation and simulation of production planning and control problems which include transfer times and stochastic influences and therefore extend classical multi-mode multi-project RCPSPs. This allows for systematic and in-depth investigations of the quality and the behaviour of heuristics. In addition, the automated design of heuristics based on Boolean operators applied to relations of problem specific quantities leads on average to better results than a manual selection and adjustment of heuristic strategies
Multiple schwannomas of the facial nerve mimicking cervical lymphoma: a case report
Background
In this report, we describe the first case in literature of a patient with multiple schwannomas of the marginal mandibular branch of the facial nerve.
Case presentation
A Caucasian patient presented with a sudden onset of left lower facial nerve palsy House–Brackmann score III for 1 month. Computed tomography imaging was performed to exclude a cerebral event and revealed multiple tumors within the left parotid gland. Duplex ultrasound and magnetic resonance imaging scans delineated multiple, hypoechoic tumors, round in shape and well defined without a hilar structure along the left mandible. For histological verification, a left-side partial parotidectomy and extirpation of an intraparotideal node was performed with use of a nerve-integrity monitor. Histomorphological analysis of the resected tissue revealed a benign schwannoma. Facial nerve function remained unchanged since the operation. The size of the nonresected tumors is currently monitored regularly by ultrasonography. Fibromatosis has been excluded.
Conclusions
If multiple tumors occur in the parotid gland and the angle of the jaw, schwannomas need to be considered as a differential diagnosis. To plan the right diagnostic surgical intervention and prevent nerve damage, a thorough ultrasound examination is essential in preoperative diagnostic work-up for any suspicious lesion of the parotid gland and jaw region
Schwannoma of the Hypoglossal Nerve Mimicking Carotid Body Paraganglioma
Carotid body paragangliomas (CBPs) clinically present as highly vascularized cervical
masses with a pathognomonic localization at the carotid artery bifurcation. Following ultrasonography and MRI/CT imaging, surgical resection with optional preoperative embolization is considered
as the treatment of choice in most cases. We herein present the case of a 60-year-old female with
characteristic clinical signs and imaging findings of a right-sided CBP who finally went to surgical
treatment. Intraoperatively, the tumor showed an adherent growth to the hypoglossal nerve that
had to be partially resected, resulting in a postoperative nerve palsy. Histological examination of
the resected tumor revealed the unexpected diagnosis of a hypoglossal nerve schwannoma. To the
best of our knowledge, we herein present the third case reported in the literature of a unilateral
hypoglossal schwannoma located at the carotid bifurcation mimicking clinical symptoms, imaging
and intraoperative findings of a CBP
Complete remission of an early-stage laryngeal cancer under combined pembrolizumab and chemotherapy treatment of a synchronous lung adenocarcinoma
Background: Anti-PD1-Checkpoint inhibition (CI) is an established treatment of recurrent and/or metastatic head
and neck cancer. A potential beneft from CI in early-stage disease that is usually treated by radiation or surgery has
not been investigated so far and is currently not addressed in clinical trials.
Case presentation: A 58-year-old man was diagnosed with a cT2 supraglottic laryngeal cancer and a synchronous
metastasized adenocarcinoma of the lung. As the patient refused any treatment of his laryngeal cancer, he received
combined immune-chemotherapy according to the KEYNOTE-189 protocol. After 4 cycles of pembrolizumab/carboplatin/pemetrexed, the patient showed a complete remission of his laryngeal cancer with a clear shrinkage of
the mediastinal and hilar lung cancer metastases. After 21 cycles of maintenance therapy, the lung adenocarcinoma
shows a stable disease status with no signs of any residual or recurrent laryngeal cancer.
Conclusions: Anti-PD1-CI may be a treatment option also for early-stage HNSCC with excellent functional outcome
when established therapies are not available
Differential nasal swab cytology represents a valuable tool for therapy monitoring but not prediction of therapy response in chronic rhinosinusitis with nasal polyps treated with Dupilumab
Introduction: Chronic Rhinosinusitis with nasal polyps (CRSwNP) is a common
chronic disease with a high impact on patients’ quality of life. If conservative and
surgical guideline treatment cannot sufficiently control disease burden,
biologicals can be considered as a comparably new treatment option that has
revolutionized CRSwNP therapy since the first approval of Dupilumab in 2019.
With the aim to select patients who benefit from this new treatment and to find a
marker for therapy monitoring, we investigated the cellular composition of nasal
mucous membranes and inflammatory cells of patients suffering from CRSwNP
and undergoing Dupilumab therapy using non-invasive nasal swab cytology.
Methods: Twenty CRSwNP patients with the indication for Dupilumab therapy
have been included in this prospective clinical study. In total, five study visits were
conducted with ambulatory nasal differential cytology using nasal swabs starting
with the beginning of therapy and followed by visits every 3 months for 12
months. First, these cytology samples were stained with the May-GrunwaldGiemsa method (MGG) and the percentage of ciliated cells, mucinous cells,
eosinophil cells, neutrophil cells, and lymphocytes was analyzed. Secondly, an
immunocytochemical (ICC) ECP-staining was performed to detect eosinophil
granulocytes. Additionally, during each study visit the nasal polyp score, SNOT20
questionnaire, olfactometry, the total IgE concentration in peripheral blood as
well as the eosinophil cell count in peripheral blood were recorded. The change
of parameters was evaluated over one year and the correlation between clinical
effectiveness and nasal differential cytology was analyzed.
Results: In both MGG (p<0.0001) and ICC analysis (p<0.001) a significant
decrease of eosinophils was seen under Dupilumab treatment. When patients
were divided into a Eo-low- (<21%) and Eo-high- (≥21%) group according to the
percentage eosinophils in nasal swab catology in the first study visit, the Eo-highgroup showed a greater change of eosinophils over time (D17.82) compared to
the Eo-low-group (D10.67) but, however, no better response to therapy. The
polyp score, SNOT20 questionnaire, and total IgE concentration in peripheral
blood showed a significant decrease during the observation period (p<0.0001).
Discussion: Nasal swab cytology as an easy-to-apply diagnostic method allows
detection and quantification of the different cell populations within the nasal
mucosa at a given time. The nasal differential cytology showed a significant
decrease of eosinophils during Dupilumab therapy and can therefore be used as
non-invasvive method for monitoring therapy success of this cost intensive
therapy and potentially can allow an optimized individual therapy planning and
management for CRSwNP patients. Since the validity of initial nasal swab
eosinophil cell count as a predictive biomarker for therapy response was
limited in our study, additional studies including larger number of participants
will be necessary to further evaluate the potential benefits for clinical practice of
this new diagnostic method
Expression of 3q Oncogene SEC62 Predicts Survival in Head and Neck Squamous Cell Carcinoma Patients Treated with Primary Chemoradiation
Primary chemoradiotherapy (CRT) is an established treatment option for locally advanced
head and neck squamous cell carcinomas (HNSCC) usually combining intensity modified radiotherapy with concurrent platinum-based chemotherapy. Though the majority of patients can be
cured with this regimen, treatment response is highly heterogeneous and can hardly be predicted.
SEC62 represents a metastasis stimulating oncogene that is frequently overexpressed in various
cancer entities and is associated with poor outcome. Its role in HNSCC patients undergoing CRT
has not been investigated so far. A total of 127 HNSCC patients treated with primary CRT were
included in this study. The median follow-up was 5.4 years. Pretherapeutic tissue samples of the
primary tumors were used for immunohistochemistry targeting SEC62. SEC62 expression, clinical
and histopathological parameters, as well as patient outcome, were correlated in univariate and
multivariate survival analyses. High SEC62 expression correlated with a significantly shorter overall
survival (p = 0.015) and advanced lymph node metastases (p = 0.024). Further significant predictors
of poor overall and progression-free survival included response to therapy (RECIST1.1), nodal status,
distant metastases, tobacco consumption, recurrence of disease, and UICC stage. In a multivariate
Cox hazard proportional regression analysis, only SEC62 expression (p = 0.046) and response to therapy (p < 0.0001) maintained statistical significance as independent predictors of the patients’ overall
survival. This study identified SEC62 as an independent prognostic biomarker in HNSCC patients
treated with primary CRT. The role of SEC62 as a potential therapeutic target and its interaction with
radiation-induced molecular alterations in head and neck cancer cells should further be investigated
Podoplanin expression in lymph node metastases of head and neck cancer and cancer of unknown primary patients
Introduction: Head and neck squamous cell carcinomas (HNSCCs) are cancers with generally poor prognosis.
Outcomes have not improved in decades, with more than half of the patients presenting with lymph node metastases
at the time of diagnosis. A unique subtype of HNSCC, cancer of unknown primary of the head and neck (HNCUP) is
associated with a poor outcome. Increased expression of the D2-40 gene (podoplanin) has been described for several
human malignancies and has been associated with increased metastatic potential of cancer cells.
Methods: In order to examine the role of podoplanin in lymph node metastasis of HNSCC generally and HNCUP specifically, we evaluated the prognostic impact of podoplanin expression in HNSCC- (n=68) and HNCUP-associated lymph
node metastases (n =30). The expression of podoplanin was analyzed by immunohistochemical staining of lymph node
tissue samples and correlated with clinical and histopathological data.
Results: We found a non-significant tendency towards a higher podoplanin expression in HNCUP compared to HNSCC
lymph node metastases and a significant correlation between a high podoplanin expression and advanced node-stage classification. Podoplanin expression had no significant impact on overall survival for both groups and did not correlate with
human papillomavirus tumor status.
Conclusion: Taken together, our results suggest that upregulation of podoplanin may be associated with a stimulation of
lymphatic metastasis in head and neck cancer
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