To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
The Eating Assessment in Toddlers FFQ (EAT FFQ) has been shown to have good reliability and comparative validity for ranking nutrient intakes in young children. With the addition of food items (n 4), we aimed to re-assess the validity of the EAT FFQ and estimate calibration factors in a sub-sample of children (n 97) participating in the Growing Up Milk – Lite (GUMLi) randomised control trial (2015–2017). Participants completed the ninety-nine-item GUMLi EAT FFQ and record-assisted 24-h recalls (24HR) on two occasions. Energy and nutrient intakes were assessed at months 9 and 12 post-randomisation and calibration factors calculated to determine predicted estimates from the GUMLi EAT FFQ. Validity was assessed using Pearson correlation coefficients, weighted kappa (κ) and exact quartile categorisation. Calibration was calculated using linear regression models on 24HR, adjusted for sex and treatment group. Nutrient intakes were significantly correlated between the GUMLi EAT FFQ and 24HR at both time points. Energy-adjusted, de-attenuated Pearson correlations ranged from 0·3 (fibre) to 0·8 (Fe) at 9 months and from 0·3 (Ca) to 0·7 (Fe) at 12 months. Weighted κ for the quartiles ranged from 0·2 (Zn) to 0·6 (Fe) at 9 months and from 0·1 (total fat) to 0·5 (Fe) at 12 months. Exact agreement ranged from 30 to 74 %. Calibration factors predicted up to 56 % of the variation in the 24HR at 9 months and 44 % at 12 months. The GUMLi EAT FFQ remained a useful tool for ranking nutrient intakes with similar estimated validity compared with other FFQ used in children under 2 years.
Using frequency-modulated continuous wave radar data from the 32nd Chinese Antarctic Research Expedition in 2015/16, subsurface profiles were obtained along an East Antarctic inland traverse from Zhongshan station to Dome A, and four distinct regions were selected to analyze the spatiotemporal variability in historical surface mass balance (SMB). Based on depth, density, and age data from ice cores along the traverse, the radar data were calibrated to yield average SMB data. The zone 49–195 km from the coast has the highest SMB (235 kg m−2 a−1). The 780–892 km zone was most affected by the Medieval Warm Period and the Little Ice Age, and the SMB during ad 1454–1836 (71 kg m−2 a−1) was only one-quarter of that in the 20th century. The SMB in the 1080–1157 km zone fluctuates the most, possibly due to erosion or irregular deposition of snow by katabatic winds in low SMB areas with surface elevation fluctuations. Dome A (1157–1236 km) has the lowest SMB (29 kg m−2 a−1) and did not decrease during Little Ice Age. Understanding the spatiotemporal variability of SMB in a larger space can help us understand the complex climate history of Antarctica.
Recognition of faces of family members, friends, and colleagues is an important skill essential for everyday life. Individuals affected by prosopagnosia (face blindness) have difficulty recognizing familiar individuals. The prevalence of prosopagnosia has been estimated to be as high as 3%. Prosopagnosia can severely impact the quality of life of those affected, and it has been suggested to co-occur with conditions such as depression and anxiety.
To determine real-world diagnostic frequency of prosopagnosia and the spectrum of its comorbidities, we utilized a large database of more than 7.5 million de-identified electronic health records (EHRs) from patients who received care at major academic health centers and Federally Qualified Health Centers in New York City. We designed a computable phenotype to search the database for diagnosed cases of prosopagnosia, revealing a total of n = 902 cases. In addition, data from a randomly sampled matched control population (n = 100,973) were drawn from the database for comparative analyses to study the condition’s comorbidity landscape. Diagnostic frequency of prosopagnosia, epidemiological characteristics, and comorbidity landscape were assessed.
We observed prosopagnosia diagnoses at a rate of 0.012% (12 per 100,000 individuals). We discovered elevated frequency of prosopagnosia diagnosis for individuals who carried certain comorbid conditions, such as personality disorder, depression, epilepsy, and anxiety. Moreover, prosopagnosia diagnoses increased with the number of comorbid conditions.
Results from this study show a wide range of comorbidities and suggest that prosopagnosia is vastly underdiagnosed. Findings imply important clinical consequences for the diagnosis and management of prosopagnosia as well as its comorbid conditions.
Leg weakness (LW) issues are a great concern for pig breeding industry. And it also has a serious impact on animal welfare. To dissect the genetic architecture of limb-and-hoof firmness in commercial pigs, a genome-wide association study was conducted on bone mineral density (BMD) in three sow populations, including Duroc, Landrace and Yorkshire. The BMD data were obtained by ultrasound technology from 812 pigs (including Duroc 115, Landrace 243 and Yorkshire 454). In addition, all pigs were genotyped using genome-by-sequencing and a total of 224 162 single-nucleotide polymorphisms (SNPs) were obtained. After quality control, 218 141 SNPs were used for subsequent genome-wide association analysis. Nine significant associations were identified on chromosomes 3, 5, 6, 7, 9, 10, 12 and 18 that passed Bonferroni correction threshold of 0.05/(total SNP numbers). The most significant locus that associated with BMD (P value = 1.92e−14) was detected at approximately 41.7 Mb on SSC6 (SSC stands for Sus scrofa chromosome). CUL7, PTK7, SRF, VEGFA, RHEB, PRKAR1A and TPO that are located near the lead SNP of significant loci were highlighted as functionally plausible candidate genes for sow limb-and-hoof firmness. Moreover, we also applied a new method to measure the BMD data of pigs by ultrasound technology. The results provide an insight into the genetic architecture of LW and can also help to improve animal welfare in pigs.
The meat quality of chicken is an important factor affecting the consumer’s health. It was hypothesized that n-3 polyunsaturated fatty acid (n-3 PUFA) could be effectively deposited in chicken, by incorporating antioxidation of soybean isoflavone (SI), which led to improved quality of chicken meat for good health of human beings. Effects of partial or complete dietary substitution of lard (LA) with linseed oil (LO), with or without SI on growth performance, biochemical indicators, meat quality, fatty acid profiles, lipid-related health indicators and gene expression of breast muscle were examined in chickens. A total of 900 males were fed a corn–soybean meal diet supplemented with 4% LA, 2% LA + 2% LO and 4% LO and the latter two including 30 mg SI/kg (2% LA + 2% LO + SI and 4% LO + SI) from 29 to 66 days of age; each of the five dietary treatments included six replicates of 30 birds. Compared with the 4% LA diet, dietary 4% LO significantly increased the feed efficiency and had no negative effect on objective indices related to meat quality; LO significantly decreased plasma triglycerides and total cholesterol (TCH); abdominal fat percentage was significantly decreased in birds fed the 4% LO and 4% LO + SI diets. Chickens with LO diets resulted in higher contents of α-linolenic acid (C18:3n-3), EPA (C20:5n-3) and total n-3 PUFA, together with a lower content of palmitic acid (C16:0), lignoceric acid (C24:0), saturated fatty acids and n-6:n-3 ratio in breast muscle compared to 4% LA diet (P < 0.05); they also significantly decreased atherogenic index, thrombogenic index and increased the hypocholesterolemic to hypercholesterolemic ratio. Adding SI to the LO diets enhanced the contents of EPA and DHA (C22:6n-3), plasma total superoxide dismutase, reduced glutathione (GSH)/oxidized glutathione and muscle GSH content, while decreased plasma total triglyceride and TCH and malondialdehyde content in plasma and breast muscle compared to its absence (P < 0.05). Expression in breast muscle of fatty acid desaturase 1 (FADS1), FADS2, elongase 2 (ELOVL2) and ELOVL5 genes were significantly higher with the LO diets including SI than with the 4% LA diet. Significant interactions existed between LO level and inclusion of SI on EPA and TCH contents. These findings indicate that diet supplemented with LO combined with SI is an effective alternative when optimizing the nutritional value of chicken meat for human consumers.
Flexibility is one of the important mechanical performance parameters of stent. The flexibility of tapered stents, especially self-expanding tapered stents, remains unknown. In this study, we developed a new selfexpanding tapered stent for tapered arteries and performed a numerical investigation of stent flexibility by using finite element method. The effect of stent design parameters, including taper and link space width, on stent flexibility was studied. The flexibility of the proposed stent was also compared with that of traditional cylindrical stents. Results show that the tapered stent is more flexible than the traditional cylindrical stent. Furthermore, the flexibility of the tapered stent increases with increasing stent taper and stent link space width. The increase in the stent link space width can contribute to the reduction in the peak stress. Therefore, tapered stents with high link space width will improve the stent flexibility. This work provides useful information for improvement of stent design and clinical selection.
Prior meta-analyses have suggested superior efficacy of venlafaxine compared to SSRIs. In this meta-analysis we compared the efficacy of venlafaxine and SSRIs in patients with MDD classified according to baseline severity
Data from 31 venlafaxine studies were pooled and remission rates defined as <8 on the HAM-D17- score were analyzed. Subjects were divided into two groups based on their baseline HAM-D-17 total score ≥30 / < 30. Fisher's exact test was used to compare the treatment effects on the remission rates for each subgroup. All of the analyses were based on intent-to-treat patients, LOCF and completer analysis were performed using standardized measurements.
5836 patients with a baseline HAM-D17 <30 could be identified. The LOCF analysis revealed, that the OR is 1.31 (95%CI 1.18, 1.46), p<0.001 and the NNT is 16, whereas the completer analysis revealed, that the OR is 1.25 (95%CI 1.09, 1.43), p=0.001 and the NNT is 16. Remission data for 656 patients with a baseline HAM-D17 >30 were available. The LOCF analysis revealed, that the OR is 1.55 (95%CI 1.10, 2.18), p=0.015 and the NNT is 11, whereas the completer analysis revealed, that the OR is 1.93 (95%CI 1.25, 2.97), p=0.003 and the NNT is 7.
This analysis demonstrates that venlafaxine is superior to SSRIs in both the mild/moderate and severe depression in achieving remission. However, the magnitude of superiority was higher in the subgroup of patients with a baseline HAM-D17 >30 suggesting a pronounced clinical benefit for the treatment of severely depressed patients.
To assess the efficacy of desvenlafaxine succinate (DVS) treatment in patients with major depressive disorder (MDD).
Seven randomized, double-blind, placebo-controlled, short-term studies were pooled to evaluate the efficacy of DVS in MDD. Adult outpatients with DSM-IV MDD were enrolled in all studies. Eligible patients were randomly assigned to DVS (n=1186) at doses of 100–400 mg/d, or placebo (n=797) for 8 weeks. The 17-item Hamilton Depression Rating Scale (HAM-D17) was the primary efficacy variable. Other efficacy variables were the Clinical Global Impressions scale (CGI), HAM-D6, Montgomery Åsberg Depression Rating Scale (MADRS), Covi Anxiety scale, Sheehan Disability Scale (SDS), WHO-5 Well-Being Index, and the Visual Analog Scale–Pain Intensity (VAS-PI). A mixed-effect model for repeated measures (MMRM) analysis was used to analyze continuous variables. Logistic regression was used to analyze response and remission rates.
An adjusted mean difference of –2.8 points on HAM-D17 total score at end point for DVS vs placebo (95% confidence limits: –2.2, –3.4; P<0.001) was demonstrated. Response and remission rates were significantly elevated for DVS-treated patients compared with placebo (P<0.001) across rating scales (HAM-D17, MADRS, and CGI). For other secondary measures at end point, including the CGI, HAM-D6, MADRS, Covi, SDS, WHO-5, and VAS-PI, significant differences from placebo were also observed. No additional benefit was observed for DVS doses above 100 mg/d in analyses of fixed-dose studies.
DVS was efficacious in treating MDD based on standard depression rating scales and measures of anxiety, global severity/improvement, functioning, well being, and pain.
To analyze baseline scores on individual items of the 17-item Hamilton Rating Scale for Depression (HAM-D17) in depressed outpatients by age groups approximating menopausal status.
This post-hoc, pooled analysis was conducted with populations from 7 double-blind, placebo-controlled desvenlafaxine succinate (DVS) trials in patients with major depressive disorder. The age groups, chosen as a proxy for pre-, peri-, and postmenopausal status, respectively, were 18-39, 40-55, and >55 years of age. Data from male patients were used to differentiate effects due to menopausal status from those related to age. Analysis of variance with Bonferroni adjustments was used to compare differences in baseline scores on individual HAM-D17 items.
A total of 1203 women (18-39 years [n=525]; 40-55 years [n=513]; >55 [n=165]) and 780 men (18-39 years [n=321]; 40-55 years [n=354]; >55 [n=105]) were included in this analysis. When analyzing these data by gender, women had significantly higher scores on HAM-D17 total (P=0.002), anxiety (P<0.001) and retardation subscales (P<0.001), and the somatic–anxiety (P<0.001), genital (P<0.001), and hypochondriasis (P=0.007) items. A significant age effect was observed for the HAM-D17 insomnia scale (P=0.004), and guilt (P<0.001), all insomnia items (P≤0.001), somatic–general (P<0.001), genital (P=0.019), and hypochondriasis (P≤0.001) individual items. An age effect among women was observed on the guilt (P=0.017), all insomnia items (P<0.05), somatic–general (P=0.022), and hypochondriasis (P=0.001) items.
Women in age groups approximating peri- and postmenopausal status had significantly higher baseline scores than younger women for the hypochondriasis, insomnia–middle and insomnia–late items of the HAM-D17.
In this meta-analysis we compared the effects of venlafaxine and SSRIs on work activity in MDD patients classified according to baseline severity
Data from the work and activity item 7 of the HAMD17 of 31 pooled studies comparing venlafaxine with SSRIs were used. Subjects were divided into two groups based on their baseline HAMD17 total score ≥30/< 30.Score distributions and the proportions of patients achieving full work functionality were summarized for both LOCF and Completers at week 8. Fisher's exact test was used to compare the treatment effects..
5836 patients with a baseline HAMD17 <30 were identified. The OR for all subjects achieving full work functionality is 1.22 (95%CI 1.08, 1.36), p<0.001 for LOCF and 1.19 (95%CI 1.04, 1.38), p=0.015 for completers. The OR for subjects with work impairment at baseline is 1.17 (95%CI 1.02, 1.35), p=0.029 for LOCF and 1.13 (95%CI 0.95, 1.35), p=0.18 for completers. 656 patients with a baseline HAMD17 >30 were identified. The OR for all subjects achieving full work functionality is 1.80 (95%CI 1.24, 2.63), p=0.002 for LOCF and 1.64 (95%CI 1.05, 2.58), p=0.032 for completers. The OR for subjects with work impairment at baseline is 1.93 (95%CI 1.30, 2.87), p=0.001 for LOCF and 1.81 (95%CI 1.12, 2.92), p=0.017 for completers.
This analysis demonstrates that venlafaxine is superior to SSRIs in improving work functionality in both mild/moderate and even more pronounced in severe depression. These results emphasize the impact of the treatment with venlafaxine on patients returning to normal social life.
Although the deviations of brain volume deficits in sporadic and familial first-episode schizophrenia patients (FEP) had been presented, the difference of brain asymmetries remained unidentified.
To assess the potential differences of volumetric asymmetries of gray matter (GM) and white matter (WM) between groups.
To find out the different injury alteration of sporadic FEP and familial FEP.
42 sporadic and 30 familiar drug-naïve FEP with and 72 matched normal controls (NC) were recruited. Participants were assessed with neuropsychological tests and scanned by a 3.0T MRI to obtain T1-weighted and DTI images. Lateralization distribution maps of GM and WM volume were generated by employing optimized voxel-based morphometry. The asymmetries were analyzed by comparing calculating Laterality Index (LI) voxel by voxel.
All three groups showed similar overall brain torque. Familiar FEP have more regional extensive GM asymmetry brain lesions compared to sporadic FEP. There was no shared regional lesion between two groups. LIGM and LIWM in right superior temporal were negatively correlated. Significant negative correlations were also found between LIGM of left superior parietal lobule and LIWM of right superior parietal lobule, and between LIGM of right inferior parietal lobule and LIWM of left inferior parietal lobule. The asymmetry in distinct brain regions were related to cognitive deficits especially in the domains of language and memory.
The two patient groups had different alteration in injuries of brain asymmetry. Familiar FEP has more GM extensive asymmetry brain region, which may correlate with their high genetic burdens.
Multiple neurotrophic factors, including vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-2, nerve growth factor (NGF) and insulin-like growth factor(IGF)-1, have been shown to play important roles in the pathophysiology of mood disorders. However, insufficient clinical data supporting the importance of these neurotrophic factors in mood disorders, especially manic episode, have made inconclusive to make a connection between these factors and the disorder.
This study intended to investigate possible peripheral biomarkers in serum of manic episode of bipolar disorder.
We aimed to investigate whether or not serum levels of VEGF, FGF-2, NGF and IGF-1 varied in manic state.
Serum levels of VEGF, FGF-2, NGF and IGF-1 were examined in 70 drug-naïve patients with manic episode of bipolar disorder (BM) as well as 50 healthy controls, using an ELISA method.
The mean serum levels of VEGF, FGF-2, NGF and IGF-1 were 168.13±225.61pg/ml, 279.09±378.62pg/ml, 61.38±171.67pg/ml and 162.01±72.00ng/ml in BM patients, and 140.80±143.71pg/ml, 275.46±235.29pg/ml, 36.34±15.14pg/ml and 138.90±80.11ng/ml in healthy controls, respectively. Serum levels of FGF-2, NGF and IGF-1 in patients were significantly higher than those in healthy controls (Z=−2.896, P=0.004; Z=− 2.050, P=0.040; Z=−2.188, P=0.029; respectively), although there was no statistical difference in the serum levels of VEGF between two groups (Z=-0.468, P=0.639). Moreover, serum levels of NGF in patients correlated with the duration of disorder (rs=−0.241, P=0.044).
The increase in serum levels of FGF-2, NGF and IGF-1 in manic state may reflect a neuroprotective role for these factors, and these factors may be considered biological markers for manic episode.
The aim of this study was to develop and externally validate a simple-to-use nomogram for predicting the survival of hospitalised human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients (hospitalised person living with HIV/AIDS (PLWHAs)). Hospitalised PLWHAs (n = 3724) between January 2012 and December 2014 were enrolled in the training cohort. HIV-infected inpatients (n = 1987) admitted in 2015 were included as the external-validation cohort. The least absolute shrinkage and selection operator method was used to perform data dimension reduction and select the optimal predictors. The nomogram incorporated 11 independent predictors, including occupation, antiretroviral therapy, pneumonia, tuberculosis, Talaromyces marneffei, hypertension, septicemia, anaemia, respiratory failure, hypoproteinemia and electrolyte disturbances. The Likelihood χ2 statistic of the model was 516.30 (P = 0.000). Integrated Brier Score was 0.076 and Brier scores of the nomogram at the 10-day and 20-day time points were 0.046 and 0.071, respectively. The area under the curves for receiver operating characteristic were 0.819 and 0.828, and precision-recall curves were 0.242 and 0.378 at two time points. Calibration plots and decision curve analysis in the two sets showed good performance and a high net benefit of nomogram. In conclusion, the nomogram developed in the current study has relatively high calibration and is clinically useful. It provides a convenient and useful tool for timely clinical decision-making and the risk management of hospitalised PLWHAs.
The fatty acid composition of chicken’s meat is largely influenced by dietary lipids, which are often used as supplements to increase dietary caloric density. The underlying key metabolites and pathways influenced by dietary oils remain poorly known in chickens. The objective of this study was to explore the underlying metabolic mechanisms of how diets supplemented with mixed or a single oil with distinct fatty acid composition influence the fatty acid profile in breast muscle of Qingyuan chickens. Birds were fed a corn-soybean meal diet supplemented with either soybean oil (control, CON) or equal amounts of mixed edible oils (MEO; soybean oil : lard : fish oil : coconut oil = 1 : 1 : 0.5 : 0.5) from 1 to 120 days of age. Growth performance and fatty acid composition of muscle lipids were analysed. LC-MS was applied to investigate the effects of CON v. MEO diets on lipid-related metabolites in the muscle of chickens at day 120. Compared with the CON diet, chickens fed the MEO diet had a lower feed conversion ratio (P < 0.05), higher proportions of lauric acid (C12:0), myristic acid (C14:0), palmitoleic acid (C16:1n-7), oleic acid (C18:1n-9), EPA (C20:5n-3) and DHA (C22:6n-3), and a lower linoleic acid (C18:2n-6) content in breast muscle (P < 0.05). Muscle metabolome profiling showed that the most differentially abundant metabolites are phospholipids, including phosphatidylcholines (PC) and phosphatidylethanolamines (PE), which enriched the glycerophospholipid metabolism (P < 0.05). These key differentially abundant metabolites – PC (14:0/20:4), PC (18:1/14:1), PC (18:0/14:1), PC (18:0/18:4), PC (20:0/18:4), PE (22:0/P-16:0), PE (24:0/20:5), PE (22:2/P-18:1), PE (24:0/18:4) – were closely associated with the contents of C12:0, C14:0, DHA and C18:2n-6 in muscle lipids (P < 0.05). The content of glutathione metabolite was higher with MEO than CON diet (P < 0.05). Based on these results, it can be concluded that the diet supplemented with MEO reduced the feed conversion ratio, enriched the content of n-3 fatty acids and modified the related metabolites (including PC, PE and glutathione) in breast muscle of chickens.
Only 30% or fewer of individuals at clinical high risk (CHR) convert to full psychosis within 2 years. Efforts are thus underway to refine risk identification strategies to increase their predictive power. Our objective was to develop and validate the predictive accuracy and individualized risk components of a mobile app-based psychosis risk calculator (RC) in a CHR sample from the SHARP (ShangHai At Risk for Psychosis) program.
In total, 400 CHR individuals were identified by the Chinese version of the Structured Interview for Prodromal Syndromes. In the first phase of 300 CHR individuals, 196 subjects (65.3%) who completed neurocognitive assessments and had at least a 2-year follow-up assessment were included in the construction of an RC for psychosis. In the second phase of the SHARP sample of 100 subjects, 93 with data integrity were included to validate the performance of the SHARP-RC.
The SHARP-RC showed good discrimination of subsequent transition to psychosis with an AUC of 0.78 (p < 0.001). The individualized risk generated by the SHARP-RC provided a solid estimation of conversion in the independent validation sample, with an AUC of 0.80 (p = 0.003). A risk estimate of 20% or higher had excellent sensitivity (84%) and moderate specificity (63%) for the prediction of psychosis. The relative contribution of individual risk components can be simultaneously generated. The mobile app-based SHARP-RC was developed as a convenient tool for individualized psychosis risk appraisal.
The SHARP-RC provides a practical tool not only for assessing the probability that an individual at CHR will develop full psychosis, but also personal risk components that might be targeted in early intervention.
Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.
To study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.
The result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.
These findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.
With growing demand for better fuel economy for automobiles, multimaterial solutions are increasingly being utilized in the automotive industry for reducing weight in the vehicle body structure. This poses challenges in terms of joining dissimilar metals, especially those with vastly different properties such as aluminum to steel joining. General Motors has developed a new resistance spot-welding technique for dissimilar materials using a multi-ring domed (MRD) electrode and multiple solidification weld schedules to address this challenge. Originally developed for aluminum to aluminum resistance spot welding, this technology is being deployed as the mainstream aluminum joining solution to leverage existing infrastructure and workforce competency in resistance spot welding. With the recent expansion of MRD technology to aluminum to steel resistance spot welding, there is an ever-greater need to experimentally verify the quality of each aluminum to steel resistance spot-weld application with limited time and resources. Nondestructive evaluation (NDE) would enable the transfer of resistance spot-welding technology to dissimilar aluminum to steel joints. This article describes the current state of the art of aluminum to steel resistance spot welding and the challenges in developing a robust NDE process for this technology.
Vaporizing foil actuator welding is a form of impact welding, which can be carried out without the use of chemical explosives. Operating at smaller length scales, but with similar driving pressures as explosive welding, vaporizing foil actuator welding is capable of welding a wide variety of advanced and dissimilar metal combinations. With negligible heating developing during the process, thermal distortion does not occur, and the base-metal properties are retained in the weld. In this article, vaporizing foil actuator welding of an automotive grade aluminum and steel pair is discussed. A currently functional and complete welding system that can be used for research as well as low volume production is also discussed.
We are developing the novel αIIbβ3 antagonist, RUC-4, for subcutaneously (SC)-administered first-point-of-medical-contact treatment for ST segment elevation myocardial infarction (STEMI).
We studied the (1) pharmacokinetics (PK) of RUC-4 at 1.0, 1.93, and 3.86 mg/kg intravenous (IV), intramuscular (IM), and SC in non-human primates (NHPs); (2) impact of aspirin on RUC-4 IC50 in human platelet-rich plasma (PRP); (3) effect of different anticoagulants on the RUC-4 IC50 in human PRP; and (4) relationship between αIIbβ3 receptor blockade by RUC-4 and inhibition of ADP-induced platelet aggregation.
(1) All doses of RUC-4 were well tolerated, but animals demonstrated variable temporary bruising. IM and SC RUC-4 reached dose-dependent peak levels within 5–15 minutes, with T1/2 s between 0.28 and 0.56 hours. Platelet aggregation studies in NHPs receiving IM RUC-4 demonstrated >80% inhibition of the initial slope of ADP-induced aggregation with all three doses 30 minutes post-dosing, with subsequent dose-dependent loss of inhibition over 4–5 hours. (2) The RUC-4 IC50 for ADP-induced platelet aggregation was unaffected by aspirin treatment (40±9 nM vs 37±5 nM; p = 0.39). (3) The RUC-4 IC50 was significantly higher in PRP prepared from D-phenylalanyl-prolyl-arginyl chloromethyl ketone (PPACK)-anticoagulated blood compared to citrate-anticoagulated blood using either thrombin receptor activating peptide (TRAP) (122±17 vs 66±25 nM; p = 0.05; n = 4) or ADP (102±22 vs 54±13; p<0.001; n = 5). (4) There was a close correspondence between receptor blockade and inhibition of ADP-induced platelet aggregation, with aggregation inhibition beginning with ~40% receptor blockade and becoming nearly complete at >80% receptor blockade.
Based on these results and others, RUC-4 has now progressed to formal preclinical toxicology studies.