From Mass Customization to Collaborative Customer CoDesign

The idea of integrating users into the design and production process is a promising strategy for companies being forced to react to the growing individualization of demand. The use of e-business applications has been discussed as a approach for mass customization for over one decade. There is a huge amount of literature on manufacturing and information systems for mass customization. However, there has been little research looking at the role of the customer within the co-design process. Customers face new uncertainties and risks (“mass confusion”) when acting as co-designers. We discuss possible risks evolving during the interaction between customers and suppliers. We propose solutions for the “mass confusion” problem, and we challenge the assumption made by most mass customization researchers that offering customized products requires an individual (one-to-one) relationship between the customer and the supplier. We envision a different way of addressing the problem by using communities instead of one-to-one relationships. The objective of our paper is to build and explore the idea of communities for customer co-design

Checklist of the Inland Fishes of Louisiana

Since the publication of Freshwater Fishes of Louisiana (Douglas, 1974) and a revised checklist (Douglas and Jordan, 2002), much has changed regarding knowledge of inland fishes in the state. An updated reference on Louisiana’s inland and coastal fishes is long overdue. Inland waters of Louisiana are home to at least 224 species (165 primarily freshwater, 28 primarily marine, and 31 euryhaline or diadromous) in 45 families. This checklist is based on a compilation of fish collections records in Louisiana from 19 data providers in the Fishnet2 network (www.fishnet2.net). The checklist has grown because of descriptions of three new species, new distribution records of both native and non-native species, and the addition numerous of marine species that are known to enter freshwaters in Louisiana

High-rate, high-resolution single photon X-ray imaging: Medipix4, a large 4-side buttable pixel readout chip with high granularity and spectroscopic capabilities

The Medipix4 chip is the latest member in the Medipix/Timepix family of hybrid pixel detector chips aimed at high-rate spectroscopic X-ray imaging using high-Z materials. It can be tiled on all 4 sides making it ideal for constructing large-area detectors with minimal dead area. The chip is designed to read out a sensor of 320 x 320 pixels with dimensions of 75 {\mu}m x 75 {\mu}m or 160 x 160 pixels with dimensions of 150 {\mu}m x 150 {\mu}m. The readout architecture features energy binning of the single photons, which includes charge sharing correction for hits with energy spread over adjacent pixels. This paper presents the specifications, architecture, and circuit implementation of the chip, along with the first electrical measurements

Risk and Clinical Risk Factors associated With Late Lower Cranial Neuropathy in Long-Term oropharyngeal Squamous Cell Carcinoma Survivors

IMPORTANCE: Lower cranial neuropathy (LCNP) is a rare, but permanent, late effect of radiotherapy and other cancer therapies. Lower cranial neuropathy is associated with excess cancer-related symptoms and worse swallowing-related quality of life. Few studies have investigated risk and clinical factors associated with late LCNP among patients with long-term survival of oropharyngeal squamous cell carcinoma (OPSCC survivors). OBJECTIVE: to estimate the cumulative incidence of and identify clinical factors associated with late LCNP among long-term OPSCC survivors. DESIGN, SETTING, AND PARTICIPANTS: This single-institution cohort study included disease-free adult OPSCC survivors who completed curative treatment from January 1, 2000, to December 31, 2013. Exclusion criteria consisted of baseline LCNP, recurrent head and neck cancer, treatment at other institutions, death, and a second primary, persistent, or recurrent malignant neoplasm of the head and neck less than 3 months after treatment. Median survival of OPSCC among the 2021 eligible patients was 6.8 (range, 0.3-18.4) years. Data were analyzed from October 12, 2019, to November 13, 2020. MAIN OUTCOMES AND MEASURES: Late LCNP events were defined by neuropathy of the glossopharyngeal, vagus, and/or hypoglossal cranial nerves at least 3 months after cancer therapy. Cumulative incidence of LCNP was estimated using the Kaplan-Meier method, and multivariable Cox proportional hazards models were fit. RESULTS: Among the 2021 OPSCC survivors included in the analysis of this cohort study (1740 [86.1%] male; median age, 56 [range, 28-86] years), 88 (4.4%) were diagnosed with late LCNP, with median time to LCNP of 5.4 (range, 0.3-14.1) years after treatment. Cumulative incidence of LCNP was 0.024 (95% CI, 0.017-0.032) at 5 years, 0.061 (95% CI, 0.048-0.078) at 10 years, and 0.098 (95% CI, 0.075-0.128) at 15 years of follow-up. Multivariable Cox proportional hazards regression identified T4 vs T1 classification (hazard ratio [HR], 3.82; 95% CI, 1.85-7.86) and accelerated vs standard radiotherapy fractionation (HR, 2.15; 95% CI, 1.34-3.45) as independently associated with late LCNP status, after adjustment. Among the subgroup of 1986 patients with nonsurgical treatment, induction chemotherapy regimens including combined docetaxel, cisplatin, and fluorouracil (TPF) (HR, 2.51; 95% CI, 1.35-4.67) and TPF with cetuximab (HR, 5.80; 95% CI, 1.74-19.35) along with T classification and accelerated radiotherapy fractionation were associated with late LCNP status after adjustment. CONCLUSIONS AND RELEVANCE: This single-institution cohort study found that, although rare in the population overall, cumulative risk of late LCNP progressed to 10% during the survivors\u27 lifetime. As expected, clinical factors associated with LCNP primarily reflected greater tumor burden and treatment intensity. Further efforts are necessary to investigate risk-reduction strategies as well as surveillance and management strategies for this disabling late effect of cancer treatment

Hypomorphic Mutations in the BCR Signalosome Lead to Selective Immunoglobulin M Deficiency and Impaired B-cell Homeostasis

B cell activation via the B cell receptor (BCR) signalosome involves participation of signaling molecules such as BTK and BLNK. Genetic defects in these molecules are known to impair B cell differentiation and subsequently lead to agammaglobulinemia. Here we identified novel mutations in BTK and BLNK in two unrelated patients that perturb the intrinsic B-cell receptor signaling pathway and lead to selective IgM deficiency, whereas production of other immunoglobulin isotypes and IgG antibody response remain intact. Currently it is unknown how BCR signaling strength affects mature B cell development in humans. Both patients show reduced levels of BCR signalosome phosphorylation as well as impaired BCR-dependent Ca2+ influx, which was accompanied by a marked decrease in IgD+IgM+CD27+ MZ-like B-cells. We further describe reduced expression of essential B cell differentiation factors such as BAFF-R and T-Bet in the patients' B-cells, which might contribute to the observed deficiency of MZ-like B cells. MZ-like B cells are known to produce natural IgM antibodies that play an essential role in immune homeostasis. By using surface plasmon resonance (SPR) technology and a synthetic blood group A trisaccharide as antigen we were able to show that both patients lack the presence of anti-blood group A IgM considered to be prototypical natural antibodies whereas IgG levels were normal. Antibody binding dynamics and binding affinity of anti-blood group A IgG were comparable between patients and healthy controls. These results indicate that human IgM deficiency can be associated with signaling defects in the BCR signalosome, defective production of natural IgM antibodies in the blood group A/B/0 system and abnormalities in B cell development

Recurrent Signature Patterns in HIV-1 B Clade Envelope Glycoproteins Associated with either Early or Chronic Infections

Here we have identified HIV-1 B clade Envelope (Env) amino acid signatures from early in infection that may be favored at transmission, as well as patterns of recurrent mutation in chronic infection that may reflect common pathways of immune evasion. To accomplish this, we compared thousands of sequences derived by single genome amplification from several hundred individuals that were sampled either early in infection or were chronically infected. Samples were divided at the outset into hypothesis-forming and validation sets, and we used phylogenetically corrected statistical strategies to identify signatures, systematically scanning all of Env. Signatures included single amino acids, glycosylation motifs, and multi-site patterns based on functional or structural groupings of amino acids. We identified signatures near the CCR5 co-receptor-binding region, near the CD4 binding site, and in the signal peptide and cytoplasmic domain, which may influence Env expression and processing. Two signatures patterns associated with transmission were particularly interesting. The first was the most statistically robust signature, located in position 12 in the signal peptide. The second was the loss of an N-linked glycosylation site at positions 413–415; the presence of this site has been recently found to be associated with escape from potent and broad neutralizing antibodies, consistent with enabling a common pathway for immune escape during chronic infection. Its recurrent loss in early infection suggests it may impact fitness at the time of transmission or during early viral expansion. The signature patterns we identified implicate Env expression levels in selection at viral transmission or in early expansion, and suggest that immune evasion patterns that recur in many individuals during chronic infection when antibodies are present can be selected against when the infection is being established prior to the adaptive immune response

[Juden in Fischach].

Letter from the teacher Michael Piller to Mrs. Eichengruen about the history of Jews in Fischach // undatedBinswangen (Dillingen an der Donau, Germany) ; Burgau (Bavaria, Germany) ; Krumbach (Günzburg, Germany)digitize