Each year, through population-based newborn screening (NBS), 1 in 294 newborns is identified with a condition leading to early treatment and, in some cases, life-saving interventions. Rapid ...advancements in genomic technologies to screen, diagnose, and treat newborns promise to significantly expand the number of diseases and individuals impacted by NBS. However, expansion of NBS occurs slowly in the United States (US) and almost always occurs condition by condition and state by state with the goal of screening for all conditions on a federally recommended uniform panel. The Newborn Screening Translational Research Network (NBSTRN) conducted the NBS Expansion Study to describe current practices, identify expansion challenges, outline areas for improvement in NBS, and suggest how models could be used to evaluate changes and improvements. The NBS Expansion Study included a workshop of experts, a survey of clinicians, an analysis of data from online repositories of state NBS programs, reports and publications of completed pilots, federal committee reports, and proceedings, and the development of models to address the study findings. This manuscript (Part One) reports on the design, execution, and results of the NBS Expansion Study. The Study found that the capacity to expand NBS is variable across the US and that nationwide adoption of a new condition averages 9.5 years. Four factors that delay and/or complicate NBS expansion were identified. A companion paper (Part Two) presents a use case for each of the four factors and highlights how modeling could address these challenges to NBS expansion.
Abstract Background and objective The survival outcomes of patients with metastatic nasopharyngeal carcinoma (NPC) differ significantly between individuals. This study aimed to evaluate whether serum ...lactic dehydrogenase (S-LDH) level had a clinical value in predicting clinical response and survival outcome for patients with metastatic NPC. Methods S-LDH level was measured at baseline and then before every cycle of treatment in 689 NPC patients with distant metastases. Correlations of pre-treatment and post-treatment S-LDH levels to response of treatment and survival were analysed retrospectively. Results Patients with elevated values of pre-treatment S-LDH (>245 IU/L) had significantly worse survival than those with normal values of pre-treatment S-LDH (⩽245 IU/L) ( P < 0.001). Patients with elevated values of post-treatment S-LDH had worse survival compared with those with normal values of post-treatment S-LDH ( P < 0.001). Patients with normal values of pre-treatment and post-treatment S-LDH showed the highest response rate and the most favourable prognosis. Conclusion S-LDH appears to be a significant independent prognostic index in patients with disseminated NPC that should be considered in the comparison of the results achieved with different therapies and in planning new randomised clinical therapeutic trials.
Minimally invasive treatment has become a mainstay management strategy for early gastric cancer (EGC). Full-thickness incision of the gastric wall using natural orifice transluminal endoscopic ...surgery (NOTES) has been reported but is not easily applicable in clinical settings at present. The aim of the current study was to assess the feasibility of hybrid NOTES, which consists of endoscopic full-thickness gastric resection and a laparoscopic lymphadenectomy.
This was a prospective, pilot study at a single tertiary care referral center. A total of 14 patients with EGC located above the lower third of the stomach underwent hybrid NOTES. Clinically, the patients had contraindications to exclusive treatment using endoscopic submucosal dissection (ESD). The main outcome measure was technical success of hybrid NOTES.
All cases were resected en bloc with negative surgical margins. Histologically, four cases were mucosal cancers, and 10 cases were submucosal cancers. The median tumor size was 26 mm (range 12 - 90 mm). Lymphatic vessel invasion was found in four cases without lymph node metastasis (LNM). The median number of obtained lymph nodes was 18 (range 7 - 67). LNM was discovered in one case of undifferentiated submucosal cancer without lymphovascular invasion. Hybrid NOTES was conducted without intraoperative or postoperative adverse events in nine cases. The median operating time and estimated blood loss of successful cases were 143 minutes (range 110 - 253 minutes) and 16 mL (range 5 - 30 mL), respectively. The median hospital stay was 6 days (range 4 - 10 days). Five cases were converted to a subtotal gastrectomy for various reasons.
Hybrid NOTES could be a bridge between endoscopic resection and laparoscopic surgery and may prevent extensive gastrectomy in patients with EGC.
To evaluate the accuracy of computed tomography (CT) texture analysis (TA) to differentiate uric acid (UA) stones from non-UA stones on unenhanced CT in patients with urinary calculi with ex vivo ...Fourier transform infrared spectroscopy (FTIR) as the reference standard.
Fourteen patients with 18 UA stones and 31 patients with 32 non-UA stones were included. All the patients had preoperative CT evaluation and subsequent surgical removal of the stones. CTTA was performed on CT images using commercially available research software. Each texture feature was evaluated using the non-parametric Mann–Whitney test. Receiver operating characteristic (ROC) curves were created and the area under the ROC curve (AUC) was calculated for texture parameters that were significantly different. The features were used to train support vector machine (SVM) classifiers. Diagnostic accuracy was evaluated.
Compared to non-UA stones, UA stones had significantly lower mean, standard deviation and mean of positive pixels but higher kurtosis (p<0.001) on both unfiltered and filtered texture scales. There were no significant differences in entropy or skewness between UA and non-UA stones. The average SVM accuracy of texture features for differentiating UA from non-UA stones ranged from 88% to 92% (after 10-fold cross validation). A model incorporating standard deviation, skewness, and kurtosis from unfiltered texture scale images resulted in an AUC of 0.965±00.029 with a sensitivity of 94.4% and specificity of 93.7%.
CTTA can be used to accurately differentiate UA stones from non-UA stones in vivo using unenhanced CT images.
•In vivo differentiating uric acid and non-uric acid stones could be achieved by CT texture analysis.•Uric acid stones had lower mean, standard deviation and mean of positive pixels but higher kurtosis.•Models incorporating different texture features could improve diagnostic accuracy.
The thermal properties of methane hydrate (MH)‐bearing sediments are necessary for developing gas production technologies (e.g., gas production rate prediction). The direct thermal property ...measurement of a general MH reservoir is difficult because it demands an advanced coring and measuring technology. Therefore, a good thermal property value estimation model for a system containing sediment grains, water, MH, and gas is necessary. In 2018, the pressure core samples were recovered from the AT‐CW1 and AT‐CW2 wells in Nankai Trough of Japan. Using a single‐sided transient plane source method, we measure herein the thermal property values of those core samples and estimate their thermal conductivity by improving existing models. The measured thermal conductivity (λ), specific heat (ρCp), and thermal diffusivity (α) of the MH‐bearing sediments before and after MH dissociation are obtained. The de Vries model agrees well with the measured thermal conductivity values before and after the MH dissociation. For the random distribution (geometric mean) model, the difference between the estimation values and the data after the MH dissociation increases as the gas saturation Sg′ increases. In the worst case, the distribution model shows an 87.6% error, while the de Vries model yields 5.2% of the same. We propose and use an estimation method of the thermal property values in an MH reservoir, which requires classical thermophysical models and well log data. The in‐situ thermal property values can be estimated when the log data are highly accurate.
Plain Language Summary
In recent years, several countries and organizations have conducted research projects on gas production from methane hydrate (MH) sediments under the ocean floor. One of the key technologies of these projects is the gas production simulator that requires physical parameter determination and models for accurate prediction. The required physical parameters remain scarce because MH dissociates under atmospheric pressure and normal temperature conditions. In this study, we measure the thermal property values of MH‐bearing sediment cores recovered from the Nankai Trough area in Japan. Various prospective models for estimating the thermal conductivity of MH‐bearing sediments have been developed, but a universally applicable unified model has not yet been created. We test classical estimation models for thermal conductivity and show that the de Vries model agrees well with the measured values of MH‐bearing sediment before and after MH dissociation. The random distribution model agrees well before dissociation, but does not agree after it. In the worst case, the random distribution model shows an 87.6% error. We propose and test an estimation method of the thermal property values obtained from an MH reservoir. The results will help in improving gas production technologies for MH deposit recovery.
Key Points
The thermal property values of 29 core samples retrieved from a gas hydrate reservoir were measured
The thermal property values before and after methane hydrate (MH) dissociation can be estimated using a classical model
We proposed and used an estimation method for thermal property values in a MH reservoir
In 2006, the European Union (EU) has decided to forbid use of antibiotics as growth promoters. Although many researches had been conducted about fiber source as alternatives of antibiotics, there are ...still lack of reports in the literature about the optimum level of sugar beet pulp supplementation, affecting growth performance and nutrient digestibility in weaning pigs. Therefore, different level of sugar beet pulp was added to diets to determine the effects of sugar beet pulp supplementation on growth performance, nutrient digestibility, fecal microflora, blood profile and incidence of diarrhea in weaning pigs.
A total of 200 weaning pigs (Yorkshire × Landrace) × Duroc, averaging 9.01 ± 1.389 kg of initial body weight were, allotted to 5 treatments in a randomized complete block (RCB) design. Each treatment was composed of 4 replicates with 10 pigs per pen. The treatments were control treatment: Corn-SBM basal diet + ZnO (phase 1: 0.05%; phase 2; 0.03%) and four different levels of sugar beet pulp were supplemented in Corn-SBM basal diet (3, 6, 9 or 12%). Two phase feeding programs (phase 1: 1-2 weeks; phase 2: 3-5 weeks) were used for 5 week of growth trial.
In feeding trial, there were no significant differences in growth performance and incidence of diarrhea among treatments. The
counts were not significantly different among dietary treatments but linear response was observed in
counts as sugar beet pulp supplementation increased (
< 0.05). In addition, IGF-1, IgA and IgG were not affected by dietary treatments. However, the BUN concentration was decreased when pigs were fed the treatments of diets with SBP compared to that of control treatment (
< 0.05). In nutrient digestibility, crude fiber and NDF digestibilities were improved as the sugar beet pulp increased (
< 0.05). However, digestibilities of crude ash, crude fat, crude fiber and nitrogen retention were not affected by dietary sugar beet pulp levels.
This experiment demonstrated that sugar beet pulp can be supplemented in weaning pigs' diet instead of ZnO to prevent postweaning diarrhea without any detrimental effect on growth performance.
Summary
Background. Exposure of human skin to ultraviolet radiation (UVR) results in erythema, pigment darkening, skin cancer and photoageing. In addition to conventional organochemical and the ...physical–mineral type sunscreens (SS), other non‐SS protective strategies have been investigated, including antioxidants (AOx) and topical DNA repair enzymes.
Aim. To investigate whether AOx could improve the protection provided by a broad‐spectrum sunscreen (SS) preparation.
Methods. Volunteers were exposed to repetitive solar‐simulated (ss)UVR at 1.5 times minimal erythema dose for four consecutive days. Thirty minutes before each exposure and 6, 24 and 48 h after the last exposure, the test materials vehicle, SS (sun protection factor 25) alone, AOx alone and SS plus AOx were applied to four different sites. Another two sites received ssUVR only, or SS plus AOx only, and a third site was left untreated (neither ssUVR or product). Erythema and pigmentation were measured using a Mexameter. Biopsy specimens were taken 72 h after the last irradiation. The thickness of the stratum corneum and epidermis were measured by microscopy. Expression of cytokeratins (CKs), matrix metalloproteinases (MMPs) and CD1a‐positive Langerhans cells (LCs) analysed by immunohistochemical staining, and relative expression levels were compared between all seven sites.
Results. AOx alone did not reduce erythema. There was a significant reduction in pigmentation, and the product almost completely protected against LC depletion. AOx plus SS gave better protection against pigment formation and CK5/6 induction than SS alone. AOx alone protected against ssUVR‐induced hyperproliferation, as shown by epidermal thickness and CK16 biomarkers, and was better than SS alone. Interestingly, although protection against induction of MMP‐9, a marker of photoageing, did not reach significance when either SS or AOx were applied separately, there was complete protection against MMP‐9 induction when these were combined.
Conclusions. Non‐SS materials such as AOx can contribute significantly to sun protection when added to a broad‐spectrum SS and applied topically to human skin in vivo.
Spatial tuning properties of retinal ganglion cells (RGCs) are sharpened by lateral inhibition originating at both the outer and inner plexiform layers. Lateral inhibition in the retina contributes ...to local contrast enhancement and sharpens edges. In this study, we used dynamic clamp recordings to examine the contribution of inner plexiform inhibition, originating from spiking amacrine cells, to the spatial tuning of RGCs. This was achieved by injecting currents generated from physiologically recorded excitatory and inhibitory stimulus-evoked conductances, into different types of primate and mouse RGCs. We determined the effects of injections of size-dependent conductances in which presynaptic inhibition and/or direct inhibition onto RGCs were partly removed by blocking the activity of spiking amacrine cells. We found that inhibition originating from spiking amacrine cells onto bipolar cell terminals and onto RGCs, work together to sharpen the spatial tuning of RGCs. Furthermore, direct inhibition is crucial for preventing spike generation at stimulus offset. These results reveal how inhibitory mechanisms in the inner plexiform layer contribute to determining size tuning and provide specificity to stimulus polarity.
A cheap, convenient and sensitive electrochemical method was developed for the determination of ciprofloxacin (CIP), one of quinolones, based on a graphene (GNs) modified glassy carbon electrode ...(GCE). Graphene oxide (GO) was prepared via improved Hummer method, and GNs were synthesised via reduction of GO using the hydrothermal method. Graphene modified GCE was obtained by dropping the GNs dispersion onto the surface of GCE and dried in air. The as prepared electrode was not only characterised by Fourier transform infrared, X-ray diffraction and SEM but also used to analyse the electrochemical behaviour of CIP. The results show that, under the optimal conditions, the oxidation peak current of CIP displays a linear response to its concentration in the range between 0·5 and 200 μmol L
− 1
with a correlation coefficient R
2
= 0·9970. The detection limit is 0·02 μmol L
− 1
at a signal/noise of 3. The analytical performance of this sensor has been evaluated for the detection of ciprofloxacin hydrochloride drugs sold in the market. The relative standard deviation (RSD) of each sample is < 5%, indicating that the as established analysis method has high accuracy and operability, which can be used for the rapid detection of the sample.
Wheat stem rust, caused by Puccinia graminis f. sp. tritici, has been effectively controlled through the use of genetic resistance. P. graminis f. sp. tritici race TTKSK (Ug99) possesses virulence to ...many resistance genes that have been used in wheat breeding worldwide. One strategy to aid breeders in developing resistant cultivars is to utilize resistance genes transferred from wild relatives to wheat. Stem rust resistance genes have previously been introgressed from Triticum monococcum to wheat. In order to identify additional resistance genes, we screened 1,061 accessions of T. monococcum and 205 accessions of T. urartu against race TTKSK and four additional P. graminis f. sp. tritici races: TTTTF, TRTTF, QFCSC, and MCCFC. A high frequency of the accessions (78.7% of T. monococcum and 93.0% of T. urartu) were resistant to P. graminis f. sp. tritici race TTKSK, with infection types ranging from 0 to 2+. Among these resistant accessions, 55 T. monococcum accessions (6.4% of the total) were also resistant to the other four races. Associations of resistance in T. monococcum germplasm to different races indicated the presence of genes conferring resistance to multiple races. Comparing the observed infection type patterns to the expected patterns of known genes indicated that previously uncharacterized genes for resistance to race TTKSK exist in both T. monococcum and T. urartu.
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