A note on ‘impacts of random scrap rate on production system in supply chain environment with a specific shipping policy’

This paper employs an alternative approach to reexamine the impacts of random scrap rate on production system in supply chain environment with a specific shipping policy. A straightforward approach in terms of a two-phase algebraic derivation is proposed in this study to replace the conventional method with the need of applying first-order and second-order differentiations to the system cost function for proof of convexity before derivation of the optimal production-shipment policy. The research result of this study is confirmed that is identical to what was obtained by Cheng et al. [1] where they used the conventional method to solve the same problem. The proposed approach is helpful for practitioners, who may not have sufficient knowledge of differential calculus to understand such an integrated production-shipment system in supply chain environment

A retrospective study on the course and outcome of fetal ventriculomegaly

AbstractObjectiveTo evaluate the outcomes associated with fetal ventriculomegaly.Materials and methodsReports of women who underwent ultrasound scanning between 18 and 36 weeks of gestation during the period from January 1, 2000, to December 31, 2010, were reviewed. According to the defined severity of ventriculomegaly of affected fetuses, the women were divided into the following groups: (1) mild ventriculomegaly (Group A); (2) moderate ventriculomegaly (Group B); and (3) severe ventriculomegaly (Group C). The women were classified into the “gray zone” group if the fetal lateral ventricle measured between 7 mm and <10 mm. All cases were followed up with additional ultrasound scans. Postnatal information was obtained from the computer database or the medical charts.ResultsA total of 41 cases were recruited for this analysis. Four (9.8%) cases had an abnormal karyotype. Twelve women (29.3%) opted for termination of pregnancy. Of the 29 women who delivered, 56.1% (N = 23) were from Group A, 14.6% (N = 6) were from Group B, and none was from Group C. All children in Group A had normal neurological development. Three children in Group B had normal neurological development, whereas the other three had neurologic deficits. A total of 432 cases were classified into the “gray zone” group. Of these cases, 2.8% (N = 12) progressed to ventriculomegaly.ConclusionCases of isolated and mild ventriculomegaly without additional structural anomalies or chromosomal aberrations had good prognoses. However, the parents of fetuses with moderate or severe ventriculomegaly should be counseled regarding related risks. If the ventricular size of the fetus falls within the “gray zone”, at least one additional exam in the third trimester should be performed, for early detection of ventriculomegaly and other related abnormalities. It is important to make the parents of these fetuses aware of these risks, from a medico-legal point of view

Clinical Implications of High MET Gene Dosage in Non-Small Cell Lung Cancer Patients without Previous Tyrosine Kinase Inhibitor Treatment

Introduction:Recently, two studies revealed that MET amplification was associated with secondary epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in non-small cell lung cancer (NSCLC) patients. But it remains uncertain whether MET amplification could be related to primary TKI resistance in NSCLC because of limited data.Materials and Methods:MET gene dosage of the tumor tissues from 208 NSCLC patients was investigated by real time quantitative polymerase chain reaction and compared with molecular and clinical features, including EGFR mutations, KRAS mutations, EGFR gene copy numbers, and patient survivals. Three copies were used as the cutoff. Among them, 25 patients were also evaluable for EGFR TKI responsiveness.Results:The proportion of high MET gene dosage was 10.58% (22/208) with higher incidence in squamous cell carcinoma (11.86%) and smokers (16.18%), although the differences with adenocarcinoma and nonsmokers were nonsignificant. Coexisting EGFR mutations were identified, and the incidence (8.54%) was similar to wild type (12.0%). High MET gene dosage was significantly associated with higher tumor stage (stage I + II versus stage III + IV; p = 0.0254) and prior chemotherapy for stage III + IV adenocarcinoma patients (35.71% versus 7.41%; p = 0.0145) but not correlated with primary TKI resistance. Among the 155 surgically resectable patients (stage I to IIIA), high MET gene dosage was significantly associated with shorter median survival (21.0 months versus 47.1 months; p = 0.042) by univariate analysis.Conclusions:High MET gene dosage was not related to primary TKI resistance and the incidence was increased after chemotherapy, suggesting high MET gene dosage may also be related to chemotherapy resistance

Genome-Wide Association Study of Young-Onset Hypertension in the Han Chinese Population of Taiwan

Young-onset hypertension has a stronger genetic component than late-onset counterpart; thus, the identification of genes related to its susceptibility is a critical issue for the prevention and management of this disease. We carried out a two-stage association scan to map young-onset hypertension susceptibility genes. The first-stage analysis, a genome-wide association study, analyzed 175 matched case-control pairs; the second-stage analysis, a confirmatory association study, verified the results at the first stage based on a total of 1,008 patients and 1,008 controls. Single-locus association tests, multilocus association tests and pair-wise gene-gene interaction tests were performed to identify young-onset hypertension susceptibility genes. After considering stringent adjustments of multiple testing, gene annotation and single-nucleotide polymorphism (SNP) quality, four SNPs from two SNP triplets with strong association signals (−log10(p)>7) and 13 SNPs from 8 interactive SNP pairs with strong interactive signals (−log10(p)>8) were carefully re-examined. The confirmatory study verified the association for a SNP quartet 219 kb and 495 kb downstream of LOC344371 (a hypothetical gene) and RASGRP3 on chromosome 2p22.3, respectively. The latter has been implicated in the abnormal vascular responsiveness to endothelin-1 and angiotensin II in diabetic-hypertensive rats. Intrinsic synergy involving IMPG1 on chromosome 6q14.2-q15 was also verified. IMPG1 encodes interphotoreceptor matrix proteoglycan 1 which has cation binding capacity. The genes are novel hypertension targets identified in this first genome-wide hypertension association study of the Han Chinese population

Identification of IGF1, SLC4A4, WWOX, and SFMBT1 as Hypertension Susceptibility Genes in Han Chinese with a Genome-Wide Gene-Based Association Study

Hypertension is a complex disorder with high prevalence rates all over the world. We conducted the first genome-wide gene-based association scan for hypertension in a Han Chinese population. By analyzing genome-wide single-nucleotide-polymorphism data of 400 matched pairs of young-onset hypertensive patients and normotensive controls genotyped with the Illumina HumanHap550-Duo BeadChip, 100 susceptibility genes for hypertension were identified and also validated with permutation tests. Seventeen of the 100 genes exhibited differential allelic and expression distributions between patient and control groups. These genes provided a good molecular signature for classifying hypertensive patients and normotensive controls. Among the 17 genes, IGF1, SLC4A4, WWOX, and SFMBT1 were not only identified by our gene-based association scan and gene expression analysis but were also replicated by a gene-based association analysis of the Hong Kong Hypertension Study. Moreover, cis-acting expression quantitative trait loci associated with the differentially expressed genes were found and linked to hypertension. IGF1, which encodes insulin-like growth factor 1, is associated with cardiovascular disorders, metabolic syndrome, decreased body weight/size, and changes of insulin levels in mice. SLC4A4, which encodes the electrogenic sodium bicarbonate cotransporter 1, is associated with decreased body weight/size and abnormal ion homeostasis in mice. WWOX, which encodes the WW domain-containing protein, is related to hypoglycemia and hyperphosphatemia. SFMBT1, which encodes the scm-like with four MBT domains protein 1, is a novel hypertension gene. GRB14, TMEM56 and KIAA1797 exhibited highly significant differential allelic and expressed distributions between hypertensive patients and normotensive controls. GRB14 was also found relevant to blood pressure in a previous genetic association study in East Asian populations. TMEM56 and KIAA1797 may be specific to Taiwanese populations, because they were not validated by the two replication studies. Identification of these genes enriches the collection of hypertension susceptibility genes, thereby shedding light on the etiology of hypertension in Han Chinese populations

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Ocular Uveitis as the Initial Presentation of Syphilis

To document the characteristics of syphilitic patients who present with ocular uveitis clinically and are diagnosed by an ophthalmologist first. Methods: Retrospective chart review of uveitis patients in the department of ophthalmology between 1992 and 2004 was done. We included only those patients with positive serologic tests, active ocular uveitis, and record of detailed examination. Results: There were 8 syphilitic patients (14 eyes) who presented with ocular syphilis clinically and who were diagnosed by an ophthalmologist first. The ocular diagnosis included panuveitis (11 eyes, 78.6%), anterior uveitis (2 eyes, 14.3%), and posterior uveitis (1 eye, 7.1%). Two patients (25%) had unilateral eye involvement, and 6 patients (75%) had involvement in bilateral eyes. One patient (2 eyes) with panuveitis also had bilateral exudative retinal detachment and chronic angle closure glaucoma. All 8 patients were negative for human immunodeficiency virus. Dark field examination of aqueous humor in 2 cases revealed Treponema pallidum, which was confirmed by immunofluorescent test. Treatment included systemic penicillin in 7 patients and oral tetracycline in 1 patient (due to penicillin allergy). Visual function and uveitis improved after treatment in all patients. Conclusion: Syphilis can be presented initially as ocular uveitis without obvious systemic manifestation. Ophthalmologists play an important role in the early diagnosis and treatment of syphilis. If treated early enough, the response is good, even if the patient is allergic to penicillin. Awareness of the multiple manifestations of ocular syphilis is the key to early detection of the disease

Early Cervical Ectopic Pregnancy: A Case Report and Review of the Literature

For women in the early stages of pregnancy, the intrauterine gestational sac cannot yet be seen. Both adnexal regions, the posterior cul-de-sac and the cervical canal should therefore be imaged to avoid missing the very rare cases of early cervical pregnancy. Color Doppler ultrasound can locate the exact site of implantation and confidently confirm the diagnosis of cervical pregnancy. Early diagnosis is important for early intervention and reduces the associated major complications