401(k) plan asset allocation, account balances, and loan activity in 2011.
THE BULK OF 401(K) ASSETS CONTINUED TO BE INVESTED IN STOCKS: On average, at year-end 2011, 61 percent of 401(k) participants' assets was invested in equity securities through equity funds, the equity portion of balanced funds, and company stock. Thirty-four percent was in fixed-income securities such as stable-value investments and bond and money funds. SEVENTY-TWO PERCENT OF 401(K) PLANS INCLUDED TARGET-DATE FUNDS IN THEIR INVESTMENT LINEUP AT YEAR-END 2011: At year-end 2011, 13 percent of the assets in the EBRI/ICI 401(k) database was invested in target-date funds and 39 percent of 401(k) participants held target-date funds. Also known as lifecycle funds, these funds are designed to offer a diversified portfolio that automatically rebalances to be more focused on income over time. MORE NEW OR RECENT HIRES INVESTED THEIR 401(K) ASSETS IN BALANCED FUNDS, INCLUDING TARGET-DATE FUNDS: For example, at year-end 2011, 51 percent of the account balances of recently hired participants in their 20s was invested in balanced funds, compared with 44 percent in 2010, and about 7 percent in 1998. A significant subset of that balanced fund category is target-date funds. At year-end 2011, 40 percent of the account balances of recently hired participants in their 20s was invested in target-date funds, compared with 35 percent at year-end 2010. 401(K) PARTICIPANTS CONTINUED TO SEEK DIVERSIFICATION OF THEIR INVESTMENTS: The share of 401(k) accounts invested in company stock remained at 8 percent in 2011. This share has fallen by more than half since 1999. Recently hired 401(k) participants contributed to this trend: They tended to be less likely to hold employer stock. PARTICIPANTS' 401(K) LOAN ACTIVITY REMAINED STEADY, ALTHOUGH LOAN BALANCES INCREASED SLIGHTLY IN 2011: At year-end 2011, 21 percent of all 401(k) participants who were eligible for loans had loans outstanding against their 401(k) accounts, unchanged from year-end 2009 and year-end 2010, and up from 18 percent at year-end 2008. Loans outstanding amounted to 14 percent of the remaining account balance, on average, at year-end 2011, unchanged from year-end 2010. Loan amounts outstanding increased slightly from those at year-end 2010. THE YEAR-END 2011 AVERAGE ACCOUNT BALANCE IN THE DATABASE WAS 2.2 PERCENT LOWER THAN THE YEAR BEFORE, BUT MAY NOT ACCURATELY REFLECT THE EXPERIENCE OF TYPICAL 401(K) PARTICIPANTS IN 2011: To understand changes in 401(k) participants' average account balances, it is important to analyze a sample of consistent participants. As with previous EBRI/ICI updates, analysis of a sample of consistent 401(k) participants (those that have been in the same plan since 2003) is expected to be published in 2013.


Risk of endometrial cancer in relationship to cigarette smoking: results from the EPIC study.
Current epidemiologic evidence indicates that cigarette smoking reduces the risk of endometrial cancer. We examined data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to analyze further aspects of the smoking-endometrial cancer relationship, such as possible modifying effects of menopausal status, HRT use, BMI and parity. In a total of 249,986 women with smoking exposure and menopausal status information, 619 incident endometrial cancer cases were identified during 1.56 million person-years of follow-up. Among postmenopausal women, the hazard ratio (HR) for current smokers versus never smokers was 0.70 (95% CI = 0.53-0.93), while it was 1.75 (95% CI = 1.13-2.70) among premenopausal women at recruitment. After adjustment for risk factors, the HR for postmenopausal women was slightly attenuated to 0.78 (95% CI = 0.59-1.03). No heterogeneity of effect was observed with HRT use or BMI. Among premenopausal women, current smokers of more than 15 cigarettes per day or who smoked for 30 years or more at the time of recruitment had a more than 2-fold increased risk of endometrial cancer compared to never smokers (HR = 2.54; 95% CI = 1.47-4.38 and HR = 2.23; 95% CI = 1.04-4.77, respectively). Past smoking was not associated with endometrial cancer risk, either among pre- or postmenopausal women. In this prospective study, we observed an increased risk of endometrial cancer with cigarette smoking in premenopausal women. The reduction of endometrial cancer risk observed among postmenopausal women does not have direct public health relevance since cigarette smoking is the main known risk factor for cancer.


Somatosensory evoked potential monitoring during carotid surgery.
Controversy exists over the value of intraoperative monitoring and shunting in patients undergoing carotid endarterectomy. Although it is widely believed that contralateral carotid occlusion and previous stroke mandate intraoperative shunting, the susceptibility of these two groups of patients to cerebral ischemia during carotid artery endarterectomy is not well defined. Somatosensory evoked potentials (SSEPs) were monitored in 113 carotid artery endarterectomy patients. Of these, 32 (28.3%) had a previous stroke, 24 (21.2%) had a contralateral carotid occlusion and 33 (29.2%) were diabetic. There were no deaths and only one perioperative stroke (0.9%). Cerebral ischemia occurred in 14 patients (12.4%). Six of these patients had a contralateral carotid occlusion. Some 29 patients (25.7%) were shunted, including 10 with contralateral carotid occlusions that did not have major SSEP changes. In the latter half of the study, 14 patients with contralateral carotid occlusions were selectively shunted (six shunted, eight not shunted) with no neurological complications. Thirty-two patients with prior strokes were selectively shunted (nine shunted, 23 not shunted); of these, one shunted patient undergoing combined carotid artery endarterectomy and coronary artery bypass grafting had a perioperative stroke. Intraoperative monitoring with SSEPs accurately identifies cerebral ischemia secondary to carotid clamping as well as patients requiring shunts. With use of intraoperative SSEP monitoring, selective shunting may be safely performed in patients with a contralateral carotid occlusion or a previous stroke.


Selective responses of visual cortical cells do not depend on shunting inhibition.
Theoretical analyses of the electrical behaviour of the highly branched processes of nerve cells has focused attention on the possibility that single cells perform complex logical operations rather than simply summing their synaptic inputs. In particular, it has been suggested that the orientation and direction selectivity of cells in the visual cortex results from the action of a nonlinear 'shunting' inhibition that emulates an AND-NOT logical operation. The characteristic biophysical feature of this proposed inhibitory mechanism is that it evokes a large and relatively sustained increase in the conductance of the neuronal membrane while leaving the membrane potential unaffected. This shunting mechanism contrasts with linear 'summative' inhibition in which conductance changes are less prominent, and inhibition is achieved by hyperpolarization of the membrane potential. In a direct experimental test of the hypothesis that the selectivity of visual cortical neurons depends on shunting inhibition we found no evidence for the large conductance changes predicted by the theory.


Decreases in implicit self-esteem explain the racial impact of microaggressions among Asian Americans.
Asian Americans are commonly perceived as perpetual foreigners and, therefore, not "true" Americans. Asian Americans report inquiries about nationality and English abilities as the most common forms of racial microaggressions perpetrated by White Americans (Sue, 2015). Race theorists assert that these microaggressions are race-related and marginalize Asian Americans. Scholars have claimed that these subtle acts are harmful, yet only a few studies have uncovered the mechanisms by which racial microaggressions affect mental and physical well-being (Ong, Burrow, Fuller-Rowell, Ja, & Sue, 2013; Wong, Derthick, David, Saw, & Okazaki, 2013). The current study conceptualized racial microaggressions as a stressor to address the major gaps in research. Specifically, this study (a) experimentally tested the race-related nature of the microaggression event to determine whether a White American perpetrator would elicit more stress in Asian Americans compared to an Asian American perpetrator and (b) examined threats to explicit and implicit self-esteem as possible mediators of microaggression-generated stress. Findings confirmed that the race of the perpetrator did have an impact on stress among Asian Americans. In the multiple meditation analysis, experience with a White American perpetrator, compared to an Asian American perpetrator, lowered implicit self-esteem, which resulted in more stress. Implications and strategies for counseling Asian American clients are discussed. (PsycINFO Database Record


Glycosaminoglycan-based hydrogels capture inflammatory chemokines and rescue defective wound healing in mice.
Excessive production of inflammatory chemokines can cause chronic inflammation and thus impair cutaneous wound healing. Capturing chemokine signals using wound dressing materials may offer powerful new treatment modalities for chronic wounds. Here, a modular hydrogel based on end-functionalized star-shaped polyethylene glycol (starPEG) and derivatives of the glycosaminoglycan (GAG) heparin was customized for maximal chemokine sequestration. The material is shown to effectively scavenge the inflammatory chemokines MCP-1 (monocyte chemoattractant protein-1), IL-8 (interleukin-8), and MIP-1α (macrophage inflammatory protein-1α) and MIP-1β (macrophage inflammatory protein-1β) in wound fluids from patients suffering from chronic venous leg ulcers and to reduce the migratory activity of human monocytes and polymorphonuclear neutrophils. In an in vivo model of delayed wound healing (db/db mice), starPEG-GAG hydrogels outperformed the standard-of-care product Promogran with respect to reduction of inflammation, as well as increased granulation tissue formation, vascularization, and wound closure.


The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements.
Piwi proteins and Piwi-interacting RNAs (piRNAs) have conserved functions in transposon silencing. The murine Piwi proteins Mili and Miwi2 (also called Piwil2 and Piwil4, respectively) direct epigenetic LINE1 and intracisternal A particle transposon silencing during genome reprogramming in the embryonic male germ line. Piwi proteins are proposed to be piRNA-guided endonucleases that initiate secondary piRNA biogenesis; however, the actual contribution of their endonuclease activities to piRNA biogenesis and transposon silencing remain unknown. To investigate the role of Piwi-catalysed endonucleolytic activity, we engineered point mutations in mice that substitute the second aspartic acid to an alanine in the DDH catalytic triad of Mili and Miwi2, generating the Mili(DAH) and Miwi2(DAH) alleles, respectively. Analysis of Mili-bound piRNAs from homozygous Mili(DAH) fetal gonadocytes revealed a failure of transposon piRNA amplification, resulting in the marked reduction of piRNA bound within Miwi2 ribonuclear particles. We find that Mili-mediated piRNA amplification is selectively required for LINE1, but not intracisternal A particle, silencing. The defective piRNA pathway in Mili(DAH) mice results in spermatogenic failure and sterility. Surprisingly, homozygous Miwi2(DAH) mice are fertile, transposon silencing is established normally and no defects in secondary piRNA biogenesis are observed. In addition, the hallmarks of piRNA amplification are observed in Miwi2-deficient gonadocytes. We conclude that cycles of intra-Mili secondary piRNA biogenesis fuel piRNA amplification that is absolutely required for LINE1 silencing.


Southerly Extension of Poplar Leaf Blight (Linospora tetraspora) in the Pacific Northwest.
Poplar leaf blight caused by Linospora tetraspora G. E. Thompson (Ascomycetes, Valsaceae) is widespread on Populus balsamifera in Canada from Quebec to British Columbia (1). The only United States records of this northerly fungus are from Vermont, Wisconsin, and Alaska (1,2). There are no records of this fungus on the Pacific Coast south of British Columbia, despite the presence of susceptible hosts (i.e., Populus trichocarpa and its hybrids). However, in September of 1997, the disease was observed in a hybrid poplar plantation at latitude 47.9°N and longitude 122.1°W near Snohomish, Washington. Blight affected the lower crown of trees in their second year of growth. Leaf lesions, with their characteristic black stromata, were easily distinguished from symptoms of other diseases. Some individual lesions of L. tetraspora affected entire leaf laminae, but there appeared to be little premature defoliation at the time of observation. Populus trichocarpa × P. deltoides hybrids were more commonly blighted than were P. trichocarpa × P. maximowiczii hybrids (i.e., 13/18 clones affected versus 4/11, respectively). A voucher specimen was deposited in the Herbarium at the Pacific Forestry Centre (DAVFP 25289). References: (1) M. E. Barr. Mycol. Mem. No. 7:130, 1978. (2) D. F. Farr. et al. 1989. Fungi on Plants and Plant Products in the United States. American Phytopathological Society, St. Paul, MN.


Invasion of dentinal tubules by oral streptococci is associated with collagen recognition mediated by the antigen I/II family of polypeptides.
Cell surface proteins SspA and SspB in Streptococcus gordonii and SpaP in Streptococcus mutans are members of the antigen I/II family of polypeptides produced by oral streptococci. These proteins are adhesins and mediate species-specific binding of cells to a variety of host and bacterial receptors. Here we show that antigen I/II polypeptides are involved in the attachment of oral streptococci to collagen and that they also determine the ability of these bacteria to invade human root dentinal tubules. Wild-type S. gordonii DL1 (Challis) cells showed heavy invasion of tubules to a depth of approximately 200 microm, whereas the abilities of cells of isogenic mutant strains OB220 (sspA) and OB219 (sspA sspB) to invade were 50 and >90% reduced, respectively. Likewise, wild-type S. mutans NG8 cells invaded dentinal tubules, whereas cells of isogenic mutant strain 834 (spaP) did not. The invasive abilities of strains OB220 and OB219 were restored by heterologous expression of S. mutans SpaP polypeptide in these strains. The extents of tubule invasion by various wild-type and mutant strains correlated with their levels of adhesion to type I collagen, a major component of dentin. Furthermore, S. gordonii DL1 cells exhibited a growth response to collagen by forming long chains. This was not shown by ssp mutants but was restored by the expression of SpaP in these cells. The production of SspA polypeptide by S. gordonii DL1, but not production of SspB polypeptide by strain OB220 (sspA), was enhanced in the presence of collagen. These results are the first to demonstrate that antigen I/II family polypeptides bind collagen and mediate a morphological growth response of streptococci to collagen. These antigen I/II polypeptide activities are critical for intratubular growth of streptococci and thus for establishment of endodontic infections.


The effect of whole-body vibration on lower extremity function in children with cerebral palsy: A meta-analysis.
The aim of this meta-analysis was to evaluate the effect of whole-body vibration training on lower limb motor function in children with cerebral palsy in randomized-controlled trials (RCTs). Two independent reviewers systematically searched the records of nine databases (PubMed, Cochrane, Web of Science, EMBASE, CNKI, etc.) from inception to December 2022. Tools from the Cochrane Collaboration were used to assess risk of bias. Standard meta-analyses were performed using Stata 16.0 and Revman 5.3. For continuous variables, the arms difference was calculated as the weighted mean difference (WMD) between the values before and after the intervention and its 95% confidence interval (95% CI). Of the 472 studies identified, 13 (total sample size 451 participants) met the inclusion criteria. Meta-analysis showed that WBV training could effectively improve GMFM88-D [WMD = 2.46, 95% CI (1.26, 3.67), P<0.01] and GMFM88-E [WMD = 3.44, 95% CI (1.21, 5.68), P = 0.003], TUG [WMD = -3.17, 95% CI (-5.11, -1.24), P = 0.001], BBS [WMD = 4.00,95% CI (3.29, 4.71), P<0. 01] and the range of motion of ankle joint and the angle of ankle joint during muscle reaction in children with cerebral palsy. The effect of WBV training on 6MWT walking speed [WMD = 47.64, 95% CI (-25.57, 120.85), p = 0.20] in children with cerebral palsy was not significantly improved. WBV training is more effective than other types of conventional physical therapy in improving the lower limb motor function of children with cerebral palsy. The results of this meta-analysis strengthen the evidence of previous individual studies, which can be applied to the clinical practice and decision-making of WBV training and rehabilitation in children with cerebral palsy.


New views on strand asymmetry in insect mitochondrial genomes.
Strand asymmetry in nucleotide composition is a remarkable feature of animal mitochondrial genomes. Understanding the mutation processes that shape strand asymmetry is essential for comprehensive knowledge of genome evolution, demographical population history and accurate phylogenetic inference. Previous studies found that the relative contributions of different substitution types to strand asymmetry are associated with replication alone or both replication and transcription. However, the relative contributions of replication and transcription to strand asymmetry remain unclear. Here we conducted a broad survey of strand asymmetry across 120 insect mitochondrial genomes, with special reference to the correlation between the signs of skew values and replication orientation/gene direction. The results show that the sign of GC skew on entire mitochondrial genomes is reversed in all species of three distantly related families of insects, Philopteridae (Phthiraptera), Aleyrodidae (Hemiptera) and Braconidae (Hymenoptera); the replication-related elements in the A+T-rich regions of these species are inverted, confirming that reversal of strand asymmetry (GC skew) was caused by inversion of replication origin; and finally, the sign of GC skew value is associated with replication orientation but not with gene direction, while that of AT skew value varies with gene direction, replication and codon positions used in analyses. These findings show that deaminations during replication and other mutations contribute more than selection on amino acid sequences to strand compositions of G and C, and that the replication process has a stronger affect on A and T content than does transcription. Our results may contribute to genome-wide studies of replication and transcription mechanisms.


Clinical vasospasm after subarachnoid hemorrhage: response to hypervolemic hemodilution and arterial hypertension.
Delayed neurologic deterioration from vasospasm remains the greatest cause of morbidity and mortality following subarachnoid hemorrhage. The authors assess the incidence and clinical course of symptomatic vasospasm following subarachnoid hemorrhage using a uniform management protocol over a 24-month period. One hundred eighteen consecutive patients were admitted to the neurovascular surgery service within 2 weeks of subarachnoid hemorrhage not attributed to trauma, tumor, or vascular malformation (113 patients had aneurysms). Early surgery was performed whenever possible, and hypertensive hypervolemic hemodilution therapy was instituted at the first sign of clinical vasospasm. Forty-two patients (35.6%) developed characteristic signs and symptoms of clinical vasospasm with angiographic verification of spasm in 39 cases. All patients with clinical vasospasm received hypervolemic hemodilution therapy aiming for a hematocrit of 33-38%, a central venous pressure of 10-12 mm Hg (or a pulmonary wedge pressure of 15-18 mm Hg), and a systolic arterial pressure of 160-200 mm Hg (120-150 mm Hg for unclipped aneurysms) for the duration of clinical vasospasm. Over the course of treatment, 60% of patients with clinical vasospasm had sustained improvement by at least 1 neurologic grade, 24% maintained a stable neurologic status, and 16% continued to worsen. At the end of hypervolemic hemodilution therapy, 47.6% had become neurologically normal, 33.3% had a minor neurologic deficit, and 19% had a major neurologic deficit or were dead. There were 3 instances of cardiopulmonary deterioration (7%), all of which were in patients without Swan-Ganz catheters, and all resolved with appropriate diuresis. One patient rebled and died while on hypervolemic hemodilution therapy.(ABSTRACT TRUNCATED AT 250 WORDS)


Psychometric evaluation of the Texas revised inventory of grief in a sample of bereaved family caregivers.
The Texas Revised Inventory of Grief (TRIG) was developed to measure the intensity of grief after the death of a close person. It consists of two scales: TRIG I (past behaviors) and TRIG II (present feelings). Because of inconsistencies in previous validations, the instrument needs to be further validated, hence the aim of this study was to evaluate the psychometric properties of the TRIG in a sample of bereaved family caregivers in Sweden. The TRIG was translated to Swedish according to standard principles, and 129 bereaved family caregivers completed the questionnaire. Parallel analysis was used to decide the number of factors to extract, followed by confirmatory factor analysis. An ordinal version of Cronbach's alpha was used to evaluate the internal consistency of the scales. Construct validity was tested against the Hospital Anxiety and Depression Scale (HADS). The factor analyses resulted in one factor being retained for both scales. The internal consistency was excellent (α > 0.9) for both scales. Construct validity was supported by strong correlations between TRIG I and TRIG II as well as moderate correlations between the TRIG scales and HADS. In conclusion, the TRIG has sound psychometric qualities and the two scales should be treated as unidimensional measures of grief. Hence, the instrument is suited to be used in the context of palliative care.


Computed tomography screening for lung cancer.
Low-dose computed tomography (CT) screening was shown to reduce lung cancer-specific mortality in a large randomized trial of a high-risk population. The decision to pursue CT screening for lung cancer is a timely question raised by individuals at risk of lung cancer and by their health care practitioners. To discuss the evidence for use of chest x-rays and low-dose CT in screening for lung cancer; to describe potential benefits, harms, and uncertainties of CT screening; and to review current guidelines for CT screening. MEDLINE and the Cochrane Library were searched from 1984 to 2012. Additional citations were obtained from lists of references from select research and review articles on this topic. Evidence was graded using the American Hospital Association level of evidence guidelines. Low-dose CT screening has been associated with a 20% reduction in lung cancer mortality in a large randomized controlled trial (National Lung Screening Trial [NLST]) of a high-risk population. Mortality data have not yet been reported for 5 other randomized controlled trials, and the sample sizes were too small to detect a meaningful difference in 2 other completed trials. A major risk of CT screening is a high false-positive rate, with associated risks and costs associated with follow-up CT scans and the potential for more invasive diagnostic procedures. Published guidelines for screening indicate a consensus that screening may be indicated for individuals who meet entry criteria for the NLST, but some guidelines expand their recommendations for screening beyond these criteria. Individuals at high risk of lung cancer who meet the criteria for CT screening in published guidelines should participate in an informed and shared decision-making process by discussing the potential benefits, harms, and uncertainties of screening with their physicians.


Development of a novel synthetic oligopeptide for the detection of DNA damage in human spermatozoa.
The integrity of DNA in spermatozoa is considered an additional parameter of semen quality and a potential fertility predictor. Significant progress has been made in recent years towards the development of reliable tests for sperm chromatin integrity and DNA damage assessment. However, most of the techniques available are labor intensive, require expensive instrumentation or utilize enzymes whose activity could be compromised by the highly condensed nature of sperm chromatin. In addition, all the methods currently available involve the destruction of the sperm tested; none is able to select intact spermatozoa that could then be used for fertilization. The aim of the present study was to create a peptide ligand-based stain, capable of binding specific DNA structures, thereby revealing the presence of DNA damage, preferably in living cells. The peptide was bioinformatically modelled on the critical region of the p53 protein associated with DNA binding and fluorescently labeled with a terminal rhodamine B dye. The ability of this 21 amino acid synthetic peptide (DW1) to detect DNA damage in intact and fixed human spermatozoa was assessed in detail. Human sperm samples (n=20) were treated with reagents that induce single- and/or double-stranded DNA breaks. The effect of these treatments on peptide-labelling was measured and compared with results obtained using established tests for the evaluation of DNA damage, such as comet assay, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and sperm chromatin dispersion test. The peptide had a high affinity for single-stranded DNA, and DNA lesions such as double- and single-stranded breaks. The proportion of spermatozoa with intense staining was found to be closely associated with the percentage of cells possessing DNA damage. The analysis of 10 sperm samples using DW1 staining and TUNEL technique showed a significant correlation between the extent of DNA fragmentation for the two methods (r=0.892, Pearson's correlation, P<0.05). We have produced a novel peptide-based stain capable of detecting DNA damage in individual sperm cells. Evaluation of sperm DNA fragmentation using this peptide may be an inexpensive and easier to use alternative to the tests in current use. Additionally, although DW1 currently requires removal of the membrane using a detergent, further research may allow this approach to be applied to the selection of viable spermatozoa with intact DNA for use in ICSI and/or intra-cytoplasmic morphologically selected sperm injection.


Population-based study of the outcome following the prenatal diagnosis of cystic hygroma.
To identify the population prevalence, pregnancy outcome, and the pattern of associated anomalies with a prenatal diagnosis of cystic hygroma. We analysed the pregnancy outcomes from 99 cases of prenatally diagnosed cystic hygroma reported to the Trent Congenital Anomalies Register from 1 January 1997 to 31 December 1999, by means of an outcome reporting form completed by the notifying centre. We identified a population prevalence of 1 in 1775 livebirths for prenatally diagnosed cystic hygroma. There were 64 terminations of pregnancy, 19 spontaneous pregnancy failures, and 16 livebirths. Of the 87 pregnancies karyotyped, 53 (61%) demonstrated aneuploidy with Turner syndrome being the most common, 29 (33%). There were a large variety of structural malformations identified, however, only 14 out of 83 terminations of pregnancy and spontaneous pregnancy failures had post-mortem examinations. Termination of pregnancy for Turner syndrome not complicated by identified structural malformations was the norm. Of the 16 livebirths, only 6 were normal at birth, 1 other has had successful hygroma surgery. Four of the liveborn infants have since died. The 'normal outcome' rate from pregnancies complicated by prenatally diagnosed cystic hygroma is less than 10% in this study (6/99). Prenatal diagnosis of cystic hygroma requires careful assessment of the fetus, with regard to both karyotyping and ultrasound. Post-mortem examination should be encouraged after termination of pregnancy, or spontaneous pregnancy loss. This is important not just to the current pregnancy but also for future pregnancies.


Developing classification criteria for polymyalgia rheumatica: comparison of views from an expert panel and wider survey.
This report summarizes the findings from a consensus process to identify potential classification criteria for polymyalgia rheumatica (PMR). A 3-stage hybrid consensus approach was used to develop potential PMR classification criteria. The first stage consisted of a facilitated meeting of 27 international experts who anonymously rated the importance of 68 potential criteria. The second stage involved a meeting of the experts, who were provided with the results of the first round of ratings and were then asked to re-rate the criteria. In the third stage, the wider acceptance of the 43 criteria that received > 50% support at round 2 was evaluated using an extended mailed survey of 111 rheumatologists and 53 nonrheumatologists in the United States, Canada, and Northern and Western Europe. A total of 68 and 50 criteria were identified and rated in round 1 and round 2, respectively. In round 2, 43 of the 50 items achieved at least 50% support, including 10 core criteria achieving 100% support. In round 3, over 70% of survey respondents agreed on the importance of 7 core criteria. These were age >or=50 years, duration >or=2 weeks, bilateral shoulder and/or pelvic girdle aching, duration of morning stiffness > 45 min, elevated erythrocyte sedimentation rate, elevated C-reactive protein, and rapid steroid response (> 75% global response within 1 wk to prednisolone/prednisone 15 20 mg daily). Among physical signs, more than 70% of survey respondents agreed on the importance of assessing pain and limitation of shoulder (84%) and/or hip (76%) on motion, but agreement was low for peripheral signs like carpal tunnel, tenosynovitis, and peripheral arthritis. There are differences in opinion as to what PMR is and how it should be treated. These findings make it important to develop classification criteria for PMR. The next step is to perform an international prospective study to evaluate the utility of candidate classification criteria for PMR in patients presenting with the polymyalgic syndrome.


Evaluation of subclinical left ventricular dysfunction in overweight people with 3D speckle-tracking echocardiography.
Obesity is associated with cardiovascular risk factors and is a major predictor of cardiovascular disease and mortality. This global burden affects myocardial function by inducing structural and functional alterations. Although subclinical left ventricular (LV) dysfunction is known in obese subjects, there is not sufficient information about overweight people. The aim of the present study was to evaluate subclinical LV dysfunction in overweight people with three-dimensional speckle-tracking echocardiography (3D-STE). One hundred eighteen consecutive patients between 18 and 80 years old were enrolled into the study. Patients were divided into three groups according to body mass index (BMI): normal (BMI: 18.5-24.9 kg/m2) (n=35), overweight (BMI: 25-29.9 kg/m2) (n=43), and obese (BMI ≥30 kg/m2) (n=40). 3D-STE was performed, and global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), and global area strain (GAS) were measured. 3D-STE results were compared between the groups. The mean age of the patients was 60.97+-8.94 years, and 55.1% of the patient population were male. Mean GCS was -13.5, GLS was -11.9, GRS was 32.3, and GAS was -22. As BMI increased, GCS and all other strain parameters were significantly worse [p<0.001 (normal-overweight), p<0.001 (normal-obese), and p<0.001 (overweight-obese) for GCS, GLS, GRS, and GAS]. A positive linear correlation was observed between BMI and all measured strain parameters (r=0.673, p<0.001 for BMI and GCS). 3D-STE is a non-invasive parameter to detect subclinical LV dysfunction, and global strain values are significantly correlated with BMI. Subclinical LV dysfunction was detected in overweight people in addition to obese subjects.


Endoluminal negative-pressure therapy for preventing rectal anastomotic leaks: a pilot study in a pig model.
Anastomotic leak after rectal resection carries substantial morbidity and mortality. A diverting ileostomy is beneficial for high-risk anastomoses, but its creation and reversal carry a surgical risk in addition to that of resection itself. We sought an alternative method for managing complications of rectal anastomosis. We developed an endoluminal negative-pressure technology with a diverting proximal sump, and hypothesized that it would close anastomotic disruptions in pigs. We performed rectal resections on pigs, with primary anastomoses and the creation of an anastomotic defect. In animals in the treatment group we inserted an endoluminal negative-pressure device and kept it at a low level of continuous suction for 5 d. No device was inserted in a control group of animals. After the 5-d period of treatment we evaluated the anastomoses in both the treatment and control groups of animals for leakage, using contrast enemas. Specimens of anastomosed rectum were evaluated histologically for mucosal integrity and for the location and density of inflammatory responses. Fourteen pigs were assigned to either the treatment (n=10) or control (n=4) group. Of the pigs in the treatment group, 90% had complete closure of their rectal defect, as compared with 25% of the animals in the control group (χ(2) test, p=0.04). The animals in the treatment group had only minimal mucosal and serosal inflammation, whereas those in the control group had extensive mucosal damage with associated serositis. Endoluminal negative-pressure therapy was well-tolerated and led to successful closure of 90% of the anastomic rectal defects in the treatment group of animals in the present study. Additional evaluation of this therapy is warranted.


Mutations causing DOK7 congenital myasthenia ablate functional motifs in Dok-7.
Dok-7 is a cytoplasmic activator of muscle-specific receptor-tyrosine kinase (MuSK). Both Dok-7 and MuSK are required for neuromuscular synaptogenesis. Mutations in DOK7 underlie a congenital myasthenic syndrome (CMS) associated with small and simplified neuromuscular synapses likely due to impaired Dok-7/MuSK signaling. The overwhelming majority of patients with DOK7 CMS have at least one allele with a frameshift mutation that causes a truncation in the COOH-terminal region of Dok-7 and affects MuSK activation. Dok-7 has pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains in the NH2-terminal moiety, both of which are indispensable for MuSK activation in myotubes, but little is known about additional functional elements. Here, we identify a chromosome region maintenance 1-dependent nuclear export signal (NES) in the COOH-terminal moiety and demonstrate that the NES-mediated cytoplasmic location of Dok-7 is essential for regulating the interaction with MuSK in myotubes. The NH2-terminal PH domain is responsible for the nuclear import of Dok-7. We also show that the Src homology 2 target motifs in the COOH-terminal moiety of Dok-7 are active and crucial for MuSK activation in myotubes. In addition, CMS-associated missense mutations found in the PH or PTB domain inactivate Dok-7. Together, these findings demonstrate that, in addition to the NH2-terminal PH and PTB domains, the COOH-terminal NES and Src homology 2 target motifs play key roles in Dok-7/MuSK signaling for neuromuscular synaptogenesis. Ablation or disruption of these functional elements in Dok-7 probably underlies the neuromuscular junction synaptopathy observed in DOK7 CMS.


Large-scale statistical analysis of secondary xylem ESTs in pine.
A computational analysis of pine transcripts was conducted to contribute to the functional annotation of conifer sequences. A statistical analysis of expressed sequential tags(ESTs) belonging the 7732 contigs in the TIGR Pinus Gene Index (PGI1.0) identified 260 differentially represented gene sequences across six cDNA libraries from loblolly pine secondary xylem. Cluster analysis of this subset of contigs resulted in five groups representing genes preferentially represented in one of the xylem samples (compression wood, plannings, root xylem, latewood) and one group containing mostly genes simultaneously present in compression and side wood libraries. To complement the sequence annotation, 27 cDNA clones representing selected transcripts were completely sequenced. Several genes were identified that could represent putative markers for xylem from different organs, at different stages of development. Several sequences encoding regulatory proteins were over-represented in root xylem as opposed to the other xylem samples. Some of them belonged to known families of plant transcription factors, but two genes were previously uncharacterized in plants. One transcript was homologous to the gene encoding the Smad4 interacting factor, a key co-activator in TGFbeta (transforming growth factor) signalling in animals. Thus, the digital analysis of pine ESTs highlighted a putative gene function of potentially broad interest but that has yet to be investigated in plants. More generally, this study showed that the application of numerical approaches to EST databases should be helpful in establishing priorities among genes to consider for targeted functional studies. Thus, we illustrated the potential of extracting information from conifer sequences already accessible through well-structured public databases.


Impacts of variable pH on stability and nutrient removal efficiency of aerobic granular sludge.
The impact of pH variation on aerobic granular sludge stability and performance was investigated. A 9-day alkaline (pH=9) and acidic (pH=6) pH shocks were imposed on mature granules with simultaneous chemical oxygen demand (COD), nitrogen and phosphorus removal. The imposed alkaline pH shock (pH 9) reduced nitrogen and phosphorus removal efficiency from 88% and 98% to 66% and 50%, respectively, with no further recovery. However, acidic pH shock (pH 6) did not have a major impact on nutrient removal and the removal efficiencies recovered to their initial values after 3 days of operation under the new pH condition. Operating the reactors under alkaline pH induced granules breakage and resulted in an increased solids concentration in the effluent and a significant decrease in the size of the bio-particles, while acidic pH did not have significant impacts on granules stability. Changes in chemical structure and composition of extracellular polymeric substances (EPS) matrix were suggested as the main factors inducing granules instability under high pH.


Celiac is a social disease: family challenges and strategies.
Celiac disease is the most common autoimmune inherited disorder in the United States, affecting approximately 1% of the population. Little research exists on the impact of family processes on adherence to a gluten-free diet (GFD), the only treatment for celiac disease. The objective of this qualitative study was to examine the barriers that families with a celiac child face and the strategies they use to adhere to the recommended diet. In-depth interviews were conducted with 10 families with a child between the ages of 6 and 12 diagnosed with celiac disease. Grounded theory and narrative analysis were used to analyze interview transcripts. Social isolation and misunderstandings about celiac disease and the GFD emerged as the most significant barriers to diet adherence including the reproduction of traditional gender relations among parents. Diet adherence facilitators included various types of institutional and societal support and idiosyncratic family arrangements. Successful diet adherence strategies used by families included planning ahead and taking their own food to social functions. Family processes play a critical role in GFD adherence. Implications for health care clinicians working with families with a child with celiac disease are discussed.


A comparison of the functional traits of common reed (Phragmites australis) in northern China: aquatic vs. terrestrial ecotypes.
Common reed (Phragmites australis (Cav.) Trin. ex Steud.) is distributed widely throughout the world with various ecotypes. This research compares the functional traits and biomass allocation patterns of two contrasting reed ecotypes. Twelve pairs of aquatic and terrestrial reed samples were collected in northern China. Significant differences in functional traits between the two reed ecotypes were observed, while biomass allocation patterns of reed organs did not differ significantly except for at the root. The dry matter content (DMC) in the whole of the reed plant, leaf, root, and rhizome was higher; while the specific leaf area (SLA) and specific root length (SRL) were lower in terrestrial versus aquatic reed. The biomass allocation in organs of the two forms of reed was isometric, only root in the terrestrial habitat increased faster with an increase in the whole plant biomass. It can be affirmed that aquatic and terrestrial reed that adapt to different environments generally has distinct leaf and root functional traits but isometric biomass allocation patterns. This suggests different resource acquisition strategies: (1) aquatic reed grows faster with high SLA and SRL and is more responsive to the environment, while (2) terrestrial reed with high DMC grows slower and is less responsive to the adverse environment (e.g. dry soil conditions).


The 3' processing of antisense RNAs physically links to chromatin-based transcriptional control.
Noncoding RNA plays essential roles in transcriptional control and chromatin silencing. At Arabidopsis thaliana FLC, antisense transcription quantitatively influences transcriptional output, but the mechanism by which this occurs is still unclear. Proximal polyadenylation of the antisense transcripts by FCA, an RNA-binding protein that physically interacts with RNA 3' processing factors, reduces FLC transcription. This process genetically requires FLD, a homolog of the H3K4 demethylase LSD1. However, the mechanism linking RNA processing to FLD function had not been established. Here, we show that FLD tightly associates with LUMINIDEPENDENS (LD) and SET DOMAIN GROUP 26 (SDG26) in vivo, and, together, they prevent accumulation of monomethylated H3K4 (H3K4me1) over the FLC gene body. SDG26 interacts with the RNA 3' processing factor FY (WDR33), thus linking activities for proximal polyadenylation of the antisense transcripts to FLD/LD/SDG26-associated H3K4 demethylation. We propose this demethylation antagonizes an active transcription module, thus reducing H3K36me3 accumulation and increasing H3K27me3. Consistent with this view, we show that Polycomb Repressive Complex 2 (PRC2) silencing is genetically required by FCA to repress FLC Overall, our work provides insights into RNA-mediated chromatin silencing.


Internet Use by Gynecologic Oncology Patients and Its Relationship with Anxiety.
This study describes the use of the Internet for health information research by patients attending a gynecologic oncology practice and examines the association between its use and anxiety. A self-administered survey assessed patients' demographic information and Internet use. The Hospital Anxiety and Depression Scale (HADS) and the State-Trait Anxiety Inventory (STAI) were administered concurrently. Of 212 patients who consented to the study, 98 (46%) had an appointment because of a cancer diagnosis. Of 199 respondents, 91 (46%) reported searching the Internet for information about their condition. Internet searching was unassociated with race/ethnicity and positively associated with education level, annual household income, and married/partnered civil status. Only 16% of the patients reported that a health-care provider recommended use of the Internet for research. Comparing patients who used the Internet for research with those who did not, the STAI state and trait anxiety scores were similar. The HADS anxiety subscale score was higher for those who used the Internet versus those who did not, which suggests heightened anxiety. Internet use for research is common in gynecologic oncology patients, and its use is associated with increased anxiety. Physicians can use this medium to educate patients about their disease, build trust, and alleviate fear.


Measurement of Muon Antineutrino Oscillations with an Accelerator-Produced Off-Axis Beam.
T2K reports its first measurements of the parameters governing the disappearance of ν[over ¯]_{μ} in an off-axis beam due to flavor change induced by neutrino oscillations. The quasimonochromatic ν[over ¯]_{μ} beam, produced with a peak energy of 0.6 GeV at J-PARC, is observed at the far detector Super-Kamiokande, 295 km away, where the ν[over ¯]_{μ} survival probability is expected to be minimal. Using a data set corresponding to 4.01×10^{20} protons on target, 34 fully contained μ-like events were observed. The best-fit oscillation parameters are sin^{2}(θ[over ¯]_{23})=0.45 and |Δm[over ¯]_{32}^{2}|=2.51×10^{-3} eV^{2} with 68% confidence intervals of 0.38-0.64 and 2.26-2.80×10^{-3} eV^{2}, respectively. These results are in agreement with existing antineutrino parameter measurements and also with the ν_{μ} disappearance parameters measured by T2K.


Transmission of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) from pre and asymptomatic infected individuals: a systematic review.
The role of SARS-Cov-2-infected persons who develop symptoms after testing (presymptomatics) or not at all (asymptomatics) in the pandemic spread is unknown. To determine infectiousness and probable contribution of asymptomatic persons (at the time of testing) to pandemic SARS-CoV-2 spread. LitCovid, medRxiv, Google Scholar, and WHO Covid-19 databases (to 31 March 2021) and references in included studies. Studies with a proven or hypothesized transmission chain based either on serial PCR cycle threshold readings and/or viral culture and/or gene sequencing, with adequate follow-up. People exposed to SARS-CoV-2 within 2-14 days to index asymptomatic (at time of observation) infected individuals. Reliability of symptom and signs was assessed within contemporary knowledge; transmission likelihood was assessed using adapted causality criteria. Systematic review. We contacted all included studies' corresponding authors requesting further details. We included 18 studies from a diverse setting with substantial methodological variation (this field lacks standardized methodology). At initial testing, prevalence of asymptomatic cases was 12.5-100%. Of these, 6-100% were later determined to be presymptomatic, this proportion varying according to setting, methods of case ascertainment and population. Nursing/care home facilities reported high rates of presymptomatic: 50-100% (n = 3 studies). Fourteen studies were classified as high risk of, and four studies as at moderate risk of symptom ascertainment bias. High-risk studies may be less likely to distinguish between presymptomatic and asymptomatic cases. Six asymptomatic studies and four presymptomatic studies reported culturing infectious virus; data were too sparse to determine infectiousness duration. Three studies provided evidence of possible and three of probable/likely asymptomatic transmission; five studies provided possible and two probable/likely presymptomatic SARS-CoV-2 transmission. High-quality studies provide probable evidence of SARS-CoV-2 transmission from presymptomatic and asymptomatic individuals, with highly variable estimated transmission rates.


Ethical machines: The human-centric use of artificial intelligence.
Today's increased availability of large amounts of human behavioral data and advances in artificial intelligence (AI) are contributing to a growing reliance on algorithms to make consequential decisions for humans, including those related to access to credit or medical treatments, hiring, etc. Algorithmic decision-making processes might lead to more objective decisions than those made by humans who may be influenced by prejudice, conflicts of interest, or fatigue. However, algorithmic decision-making has been criticized for its potential to lead to privacy invasion, information asymmetry, opacity, and discrimination. In this paper, we describe available technical solutions in three large areas that we consider to be of critical importance to achieve a human-centric AI: (1) privacy and data ownership; (2) accountability and transparency; and (3) fairness. We also highlight the criticality and urgency to engage multi-disciplinary teams of researchers, practitioners, policy makers, and citizens to co-develop and evaluate in the real-world algorithmic decision-making processes designed to maximize fairness, accountability, and transparency while respecting privacy.


Sex-Based Differences in Cortical and Subcortical Development in 436 Individuals Aged 4-54 Years.
Sex-based differences in brain development have long been established in ex vivo studies. Recent in vivo studies using magnetic resonance imaging (MRI) have offered considerable insight into sex-based variations in brain maturation. However, reports of sex-based differences in cortical volumes and thickness are inconsistent. We examined brain maturation in a cross-sectional, single-site cohort of 436 individuals (201 [46%] males) aged 4-54 years (median = 16 years). Cortical thickness, cortical surface area, subcortical surface area, volumes of the cerebral cortex, white matter (WM), cortical and subcortical gray matter (GM), including the thalamic subnuclei, basal ganglia, and hippocampi were calculated using automatic segmentation pipelines. Subcortical structures demonstrated distinct curvilinear trajectories from the cortex, in both volumetric maturation and surface-area expansion in relation to age. Surface-area analysis indicated that dorsal regions of the thalamus, globus pallidus and striatum, regions demonstrating structural connectivity with frontoparietal cortices, exhibited extensive expansion with age, and were inversely related to changes seen in cortical maturation, which contracted with age. Furthermore, surface-area expansion was more robust in males in comparison to females. Age- and sex-related maturational changes may reflect alterations in dendritic and synaptic architecture known to occur during development from early childhood through to mid-adulthood.


Maternal diet and dioxin-like activity, bulky DNA adducts and micronuclei in mother-newborns.
Maternal diet can contribute to carcinogenic exposures and also modify effects of environmental exposures on maternal and fetal genetic stability. In this study, associations between maternal diet and the levels of dioxin-like plasma activity, bulky DNA adducts in white blood cells and micronuclei (MN) in lymphocytes from mother to newborns were examined. From 98 pregnant women living in the greater area of Copenhagen, Denmark in 2006-2007, maternal peripheral blood and umbilical cord blood were collected, together with information on health, environmental exposure and lifestyle. Maternal diet was estimated on the basis of maternal food frequency questionnaire (FFQ) completed by the end of pregnancy. Biomarkers were detected in paired blood samples through the dioxin-responsive chemical-activated luciferase expression (CALUX)(®) bioassay, (32)P-postlabelling technique and cytokinesis-block MN assay. Maternal preference for meats with dark surface were significantly associated with higher bulky DNA adducts in both maternal (β 95%CI; 0.46 (0.08, 0.84)) and cord blood (β 95%CI; 0.46 (0.05, 0.86)) before and after adjustment for potential confounders. No other significant associations between the 18 dietary variables and the biomarkers measured in maternal and fetal samples were identified. The present study suggests that maternal intake of meats with dark surface contributes to the bulky DNA adduct levels in maternal and umbilical cord blood. Relationship between food preparation and bulky DNA adducts appear to be captured by a FFQ while potential associations for other biomarkers might be more complex or need larger sample size.


The AD7C-NTP neuronal thread protein biomarker for detecting Alzheimer's disease
Dementia in Alzheimer's disease (AD) is ultimately due to cell loss mediated by several mechanisms including, apoptosis, impaired mitochondrial function, and possibly necrosis. A second major neuroanatomic correlate of dementia is aberrant cortical neuritic sprouting with abundant proliferation of dystrophic neurites. Early in vivo detection of AD will require non-invasive assays of highly sensitive and relatively specific biomarkers that reflect these fundamental abnormalities in cellular function. The AD-associated neuronal thread protein (AD7c-NTP) gene encodes an approximately 41 kD membrane-spanning phosphoprotein that causes apoptosis and neuritic sprouting in transfected neuronal cells. The AD7c-NTP gene is over-expressed in AD beginning early in the course of disease. In the brain, increased AD7c-NTP immunoreactivity is associated with phospho-tau-immunoreactive cytoskeletal lesions, but not with amyloid-? accumulations. The levels of AD7c-NTP in postmortem brain tissue correlate with the levels measured in paired ventricular fluid samples, suggesting that the protein is secreted or released by dying cells into cerebrospinal fluid (CSF). In this regard, elevated levels of AD7c-NTP can be detected in both CSF and urine of patients with early or moderately severe AD, and the CSF and urinary levels of AD7c-NTP correlate with the severity of dementia. The newest configuration of the AD7c-NTP assay, termed "7c Gold", has greater than 90% sensitivity and specificity for detecting early AD. The aggregate results from a number of studies suggest that AD7c-NTP is an excellent biomarker that could be helpful in the routine clinical evaluation of elderly patients at risk for AD.


Evaluation of pneumococcal vaccination rates after vaccine protocol changes and nurse education in a tertiary care teaching hospital.
Pneumococcal vaccination in eligible patients is recommended by the Infectious Disease Society of America and the Centers for Disease Control (CDC) Advisory Committee on Immunization Practices. Because hospitalization provides an opportunity to vaccinate patients at high risk for developing serious pneumonia complications, eligibility screening and administration of the pneumococcal vaccine prior to discharge in qualified patients are evaluated by the Joint Commission and the Centers for Medicare Medicaid Services (CMS) as part of pneumococcal vaccination core quality measures. Among patients with an inpatient diagnosis of pneumonia in 2008, 56% in our 580-bed tertiary care teaching hospital, compared with 84% nationwide, received pneumococcal vaccination. To improve pneumococcal vaccination rates for all patients in the study facility and not just those with pneumonia, a multifaceted intervention including a revised nurse screening tool, rescheduling of the vaccine order, storage of the vaccine in automated dispensing cabinets on the nursing unit, and creation of a vaccine tracking system was developed and implemented between August 2009 and October 2009. To determine the impact of a multifaceted intervention on pneumococcal vaccine screening and administration rates in eligible patients according to the CDC recommendations who were admitted to an internal medicine unit of a tertiary care teaching hospital. All patients aged 18 years or older from 2 internal medicine units were identified during 4-month time intervals before (pre-intervention, April through July 2009) and after (post-intervention, November 2009 through February 2010) implementation of the multifaceted pneumococcal vaccine protocol. Of these, 150 patients from each 4-month period were randomly selected for electronic medical record review. Eligibility for pneumococcal vaccination was derived from the CDC recommendations and consensus of the vaccine steering committee at the study institution; the criteria included aged 65 years or older, admitting diagnosis of pneumonia, at least 1 of several chronic diseases, immunocompromising condition, cochlear implant, cerebrospinal fluid leak, current tobacco smoking, pregnancy or having a child in the home less than aged 6 months, or awaiting solid organ transplantation. Patients who had vaccine contraindications/precautions or had been vaccinated in the previous 5 years were ineligible. Data on demographics, presence of vaccine screening, indication, administration, rescheduling, and refusal were collected. The primary endpoint was the rate of pneumococcal vaccine administration in eligible medicine patients. Secondary endpoints included changes in screening rates, vaccine refusal, and order rescheduling. Descriptive statistics and Student's t-test were used to evaluate patient demographic data. Pearson chi-square was used to compare the pre- and post-implementation periods. The rate of pneumococcal vaccine administration in eligible patients significantly improved post-implementation compared with pre-implementation (74.2% vs. 19.1%, respectively, P < 0.001). Rates of vaccine screening were similar pre-implementation (96.0%) and post-implementation (99.3%, P = 0.056). The rates of vaccine refusal in the pre- and post-implementation periods did not significantly differ (10.6% vs. 22.6%, respectively, P = 0.203). Implementation of vaccine protocol changes was associated with improved pneumococcal vaccination rates in eligible medicine patients. Protocol changes were relatively easy to implement in a large institution, and a similar approach may be implemented at other institutions as an effective way to improve pneumococcal vaccination rates.


Color-changing and color-tunable photonic bandgap fiber textiles.
We present the fabrication and use of plastic Photonic Band Gap Bragg fibers in photonic textiles for applications in interactive cloths, sensing fabrics, signage and art. In their cross section Bragg fibers feature periodic sequence of layers of two distinct plastics. Under ambient illumination the fibers appear colored due to optical interference in their microstructure. Importantly, no dyes or colorants are used in fabrication of such fibers, thus making the fibers resistant to color fading. Additionally, Bragg fibers guide light in the low refractive index core by photonic bandgap effect, while uniformly emitting a portion of guided color without the need of mechanical perturbations such as surface corrugation or microbending, thus making such fibers mechanically superior to the standard light emitting fibers. Intensity of side emission is controlled by varying the number of layers in a Bragg reflector. Under white light illumination, emitted color is very stable over time as it is defined by the fiber geometry rather than by spectral content of the light source. Moreover, Bragg fibers can be designed to reflect one color when side illuminated, and to emit another color while transmitting the light. By controlling the relative intensities of the ambient and guided light the overall fiber color can be varied, thus enabling passive color changing textiles. Additionally, by stretching a PBG Bragg fiber, its guided and reflected colors change proportionally to the amount of stretching, thus enabling visually interactive and sensing textiles responsive to the mechanical influence. Finally, we argue that plastic Bragg fibers offer economical solution demanded by textile applications.


Expression of functional beta-adrenoceptors and polyploidy development in cultured vascular smooth muscle cells from spontaneously hypertensive rats.
The main objective of this study was to investigate the role of beta-adrenoceptor activation in the development of polyploidy in these cells. Smooth muscle cells (SMCs) were cultured from 3- to 4-, 10- to 12-, and 28- to 30-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Functional expression of beta-adrenoceptors was examined by treatment of cultured SMCs with a nonselective beta-adrenoceptor agonist, isoproterenol, or an adenylate cyclase activator, forskolin, or a membrane-permeable analog of adenosine 3',5'-cyclic monophosphate (cAMP), 8-bromo-cAMP, and the measurement of intracellular cAMP levels, using a radioimmunoassay. The effects of these treatments on polyploidy development were also studied by measuring the DNA content of SMCs, using scanning microdensitometry. Treatments with isoproterenol or forskolin increased intracellular cAMP levels in both strains of rats in all three age groups. Addition of the beta-adrenoceptor antagonist DL-propranolol inhibited the isoproterenol-stimulated response in SMCs from both SHR and WKY in all three age groups. The number of polyploid SMCs was significantly increased by treatments with isoproterenol, forskolin, or 8-bromo-cAMP in SMCs from 3- to 4-week-old WKY and SHR, but in the 10- to 12-week age group, an increase was found only in SMCs from WKY. Such treatments had no effect on the incidence of polyploid SMCs in the 28- to 30-week groups. We conclude that (i) beta-adrenoceptors expressed by the SMCs from WKY and SHR at all three ages are functional and are coupled via Gs proteins to the stimulation of adenylate cyclase, (ii) treatments that elevate intracellular cAMP levels (by activation of beta-adrenoceptors or of adenylate cyclase) lead to increased polyploid SMCs from WKY and SHR in the younger age group, confirming a role for the beta-adrenoceptor-adenylate cyclase pathway in the development of polyploidy in cultured SMCs from both of these strains of rats, and (iii) the absence of these treatment effects in the induction of polyploid SMCs in older age groups suggests that in these cells, other factors or processes may be involved in regulating the development of polyploid SMCs.


Test for positional candidate genes for body composition on pig chromosome 6.
One QTL affecting backfat thickness (BF), intramuscular fat content (IMF) and eye muscle area (MA) was previously localized on porcine chromosome 6 in an F2 cross between Iberian and Landrace pigs. This work was done to study the effect of two positional candidate genes on these traits: H-FABP and LEPR genes. The QTL mapping analysis was repeated with a regression method using genotypes for seven microsatellites and two PCR-RFLPs in the H-FABP and LEPR genes. H-FABP and LEPR genes were located at 85.4 and 107 cM respectively, by linkage analysis. The effects of the candidate gene polymorphisms were analyzed in two ways. When an animal model was fitted, both genes showed significant effects on fatness traits, the H-FABP polymorphism showed significant effects on IMF and MA, and the LEPR polymorphism on BF and IMF. But when the candidate gene effect was included in a QTL regression analysis these associations were not observed, suggesting that they must not be the causal mutations responsible for the effects found. Differences in the results of both analyses showed the inadequacy of the animal model approach for the evaluation of positional candidate genes in populations with linkage disequilibrium, when the probabilities of the parental origin of the QTL alleles are not included in the model.


Characteristics of COPD in never-smokers and ever-smokers in the general population: results from the CanCOLD study.
There is limited data on the risk factors and phenotypical characteristics associated with spirometrically confirmed COPD in never-smokers in the general population. To compare the characteristics associated with COPD by gender and by severity of airway obstruction in never-smokers and in ever-smokers. We analysed the data from 5176 adults aged 40 years and older who participated in the initial cross-sectional phase of the population-based, prospective, multisite Canadian Cohort of Obstructive Lung Disease study. Never-smokers were defined as those with a lifetime exposure of <1/20 pack year. Logistic regressions were constructed to evaluate associations for 'mild' and 'moderate-severe' COPD defined by FEV1/FVC <5th centile (lower limits of normal). Analyses were performed using SAS V.9.1 (SAS Institute, Cary, North Carolina, USA). The prevalence of COPD (FEV1/FVC<lower limits of normal) in never-smokers was 6.4%, constituting 27% of all COPD subjects. The common independent predictors of COPD in never-smokers and ever-smokers were older age, self reported asthma and lower education. In never-smokers a history of hospitalisation in childhood for respiratory illness was discriminative, while exposure to passive smoke and biomass fuel for heating were discriminative for women. COPD in never-smokers and ever-smokers was characterised by increased respiratory symptoms, 'respiratory exacerbation' events and increased residual volume/total lung capacity, but only smokers had reduced DLCO/Va and emphysema on chest CT scans. The study confirmed the substantial burden of COPD among never-smokers, defined the common and gender-specific risk factors for COPD in never-smokers and provided early insight into potential phenotypical differences in COPD between lifelong never-smokers and ever-smokers. NCT00920348 (ClinicalTrials.gov); study ID number: IRO-93326.


Effects of organic and conventional growth systems on the content of carotenoids in carrot roots, and on intake and plasma status of carotenoids in humans.
The demand for organic food products has increased during the last decades due to their probable health effects, among others. A higher content of secondary metabolites such as carotenoids in organic food products has been claimed, though not documented, to contribute to increased health effects of organic foods. The aim was to study the impact of organic and conventional agricultural systems on the content of carotenoids in carrots and human diets. In addition, a human cross-over study was performed, measuring the plasma status of carotenoids in humans consuming diets made from crops from these agricultural systems. The content of carotenoids in carrot roots and human diets was not significantly affected by the agricultural production system or year, despite differences in fertilisation strategy and levels. The plasma status of carotenoids increased significantly after consumption of the organic and conventional diets, but no systematic differences between the agricultural production systems were observed. The expected higher content of presumed health-promoting carotenoids in organic food products was not documented in this study.


Informing the Design of Direct-to-Consumer Interactive Personal Genomics Reports.
In recent years, people who sought direct-to-consumer genetic testing services have been increasingly confronted with an unprecedented amount of personal genomic information, which influences their decisions, emotional state, and well-being. However, these users of direct-to-consumer genetic services, who vary in their education and interests, frequently have little relevant experience or tools for understanding, reasoning about, and interacting with their personal genomic data. Online interactive techniques can play a central role in making personal genomic data useful for these users. We sought to (1) identify the needs of diverse users as they make sense of their personal genomic data, (2) consequently develop effective interactive visualizations of genomic trait data to address these users' needs, and (3) evaluate the effectiveness of the developed visualizations in facilitating comprehension. The first two user studies, conducted with 63 volunteers in the Personal Genome Project and with 36 personal genomic users who participated in a design workshop, respectively, employed surveys and interviews to identify the needs and expectations of diverse users. Building on the two initial studies, the third study was conducted with 730 Amazon Mechanical Turk users and employed a controlled experimental design to examine the effectiveness of different design interventions on user comprehension. The first two studies identified searching, comparing, sharing, and organizing data as fundamental to users' understanding of personal genomic data. The third study demonstrated that interactive and visual design interventions could improve the understandability of personal genomic reports for consumers. In particular, results showed that a new interactive bubble chart visualization designed for the study resulted in the highest comprehension scores, as well as the highest perceived comprehension scores. These scores were significantly higher than scores received using the industry standard tabular reports currently used for communicating personal genomic information. Drawing on multiple research methods and populations, the findings of the studies reported in this paper offer deep understanding of users' needs and practices, and demonstrate that interactive online design interventions can improve the understandability of personal genomic reports for consumers. We discuss implications for designers and researchers.


Fertility traits in spring-calving Aberdeen Angus cattle. 2. Model comparison.
The aim of this study was to investigate the possible superiority of a threshold-linear (TL) approach for calving day (CD) and calving success (CS) analysis in beef cattle over 2 multiple-trait (MT), censored models, considering CD at the first 3 calving opportunities. The CD observations on animals that failed to calve in the latter models were defined as cows being assigned a penalty value of 21 d beyond the last observed CD record within contemporary group (PEN model) or censored CD values that were randomly obtained from a truncated normal distribution (CEN-model). In the TL model, CD records were treated as missing if a cow failed to calve, and parameters were estimated in a TL analysis including CS traits (TLMISS-model). The models included the effects of contemporary group (herd x year of calving x mating management), age at calving, physiological status at mating (lactating or nonlactating cow), animal additive genetic effects, and residual. Field data included 6,763 calving records obtained from first, second, and third parities of 3,442 spring-calving Uruguayan Aberdeen Angus cows. Models were contrasted using a data splitting technique, analyzing correlations between predicted breeding values (PBV) for each pair of subsamples, by rank correlations between PBV obtained with the different models, and by inspecting percentage of sires selected in common using the different approaches at 10 and 25% hypothetical percentages of animals selected. Breeding value correlations of CD between the subsamples for the TLMISS approach were greater (0.67 to 0.68) than correlations for the censored MT models (0.49 to 0.54). Average correlations between PBV of CD in 1 subsample obtained by CEN (PEN, TLMISS) and PBV of CS in the other subsample were -0.53 (-0.55, -0.60) in the first calving opportunity (CO), -0.54 (-0.58, -0.63) in the second CO, and -0.50 (-0.49, -0.58) in the third CO. Rank correlations between PBV for CD in PEN and CEN were high (0.93 to 0.97), but correlations of either method with PBV of CD in TLMISS ranged from 0.50 to 0.71. Common identification of bulls for the top 10% of sires (25% of sires), when selected with PEN/CEN models or the TLMISS model, varied between 50 (44%) and 60 (52%). The use of the TL animal model for genetic evaluation seems attractive for genetic evaluation of fertility traits in beef cattle.


p190RhoGAP proteins contain pseudoGTPase domains.
The two p190RhoGAP proteins, p190RhoGAP-A and -B, are key regulators of Rho GTPase signaling and are essential for actin cytoskeletal structure and contractility. Here we report the discovery of two evolutionarily conserved GTPase-like domains located in the 'middle domain', previously thought to be unstructured. Deletion of these domains reduces RhoGAP activity. Crystal structures, MANT-GTPγS binding, thermal denaturation, biochemical assays and sequence homology analysis all strongly support defects in nucleotide-binding activity. Analysis of p190RhoGAP proteins therefore indicates the presence of two previously unidentified domains which represent an emerging group of pseudoenzymes, the pseudoGTPases.A growing number of 'pseudoenzymes' with a regulatory role in signal transduction processes but without catalytic activity are being identified. Here, the authors identify two pseudoGTPase domains in p190RhoGAP, characterize them biochemically and structurally and show that they influence RhoGAP activity.


Craniofacial phenotypes in segmentally trisomic mouse models for Down syndrome.
Trisomy for chromosome 21 (Chr 21) has profound effects on development that result in a constellation of phenotypes known as Down syndrome (DS). Distinctive craniofacial manifestations are among the few features common to all individuals with DS. The characteristic face of a person with DS results primarily from maldevelopment of the underlying craniofacial skeleton. The Ts65Dn mouse, which has segmental trisomy 16, producing dosage imbalance for about half the genes found on human Chr 21, exhibits specific skeletal malformations corresponding directly to the craniofacial dysmorphogenesis in DS. Here we demonstrate that Ts1Cje mice, which are at dosage imbalance for about 3/4 of the genes triplicated in Ts65Dn, demonstrate a very similar pattern of anomalies in the craniofacial skeleton. However, one characteristic of Ts65Dn mice, a broadening of the cranial vault contributing to brachycephaly, is not seen in Ts1Cje mice. These observations independently confirm that a dosage imbalance for mouse genes orthologous to those on human Chr 21 has corresponding effects in both species. The subtle differences in the craniofacial phenotypes of Ts1Cje and Ts65Dn mice have implications for elucidation of the mechanisms by which this aneuploidy disrupts development.


Predictive genetic testing for adult-onset disorders in minors: a critical analysis of the arguments for and against the 2013 ACMG guidelines.
The publication of the ACMG recommendations has reignited the debate over predictive testing for adult-onset disorders in minors. Response has been polarized. With this in mind, we review and critically analyze this debate. First, we identify long-standing inconsistencies between consensus guidelines and clinical practice regarding risk assessment for adult-onset genetic disorders in children using family history and molecular analysis. Second, we discuss the disparate assumptions regarding the nature of whole genome and exome sequencing underlying arguments of both supporters and critics, and the role these assumptions play in the arguments for and against reporting. Third, we suggest that implicit differences regarding the definition of best interests of the child underlie disparate conclusions as to the best interests of children in this context. We conclude by calling for clarity and consensus concerning the central foci of this debate.


Sleep trends of active-duty service members referred for psychiatric care: a descriptive study.
Military service members have unique experiences that may contribute to sleep problems in this patient population. To gather sleep habits and chronic sleep complaints among active-duty service members to identify common characteristics. The investigators administered a detailed sleep log, the Pittsburgh Insomnia Rating Scale, the Zung Self-Rating Depression Scale, the Epworth Sleepiness Scale, and the Pre-Sleep Arousal Scale to consenting service members referred to a military psychiatric partial hospitalization program. A total of 57 service members participated in this study. Participants reported a mean of less than 5 total hours of sleep and sleep latencies of 30 minutes or more. Tobacco users (n=22) reported nearly a full hour less of total time slept. Service members with combat experience (n=26) reported qualitatively poorer sleep with less total sleep time (P=.05), greater presleep arousal (P=.01), and a substantially greater number of troubling dreams (P=.06) compared with service members without combat experience. Chronic sleep issues are common complaints among military personnel, an anecdotal finding confirmed by the results of this study. These results lend support for more detailed sleep assessments, particularly among combat veterans.


Development of a flow-through optosensor for determination of Co(II).
A flow-through optical fibre chemical sensor for the determination of Co(II) at trace level using immobilised 2-(4-pyridylazo)resorcinol (PAR) as the reagent phase is proposed. PAR is physically adsorbed onto XAD-7. This method provided a great sensitivity and simplicity with wide linear response range from 1x10(-2) to 1x10(3)ppm and detection limit of 20ppb. This method also showed a reproducible result with relative standard deviation (R.S.D.) of 1.78% and response time of approximately 5min. The response towards Co(II) was also reversible using acidified KCl as the regenerating solution. Interference studies showed that Cr(III) significantly interfered during the determination. Excellent agreement with reference to inductively coupled plasma optical emission spectroscopy (ICPOES) method was achieved when the developed sensor was applied for determination of Co(II) in aqueous samples.


Molecular characterization of Giardia intestinalis haplotypes in marine animals: variation and zoonotic potential.
Giardia intestinalis is a microbial eukaryotic parasite that causes diarrheal disease in humans and other vertebrates worldwide. The negative effect on quality of life and economics caused by G. intestinalis may be increased by its potential status as a zoonosis, or a disease that can be transmitted from animals to humans. The zoonotic potential of G. intestinalis has been implied for over 2 decades, with human-infecting genotypes (belonging to the 2 major subgroups, Assemblages A and B) occurring in wildlife and domesticated animals. There are recent reports of G. intestinalis in shellfish, seals, sea lions and whales, suggesting that marine animals are also potential reservoirs of human disease. However, the prevalence, genetic diversity and effect of G. intestinalis in marine environments and the role that marine animals play in transmission of this parasite to humans are relatively unexplored. Here, we provide the first thorough molecular characterization of G. intestinalis in marine vertebrates. Using a multi-locus sequencing approach, we identify human-infecting G. intestinalis haplotypes of both Assemblages A and B in the fecal material of dolphins, porpoises, seals, herring gulls Larus argentatus, common eiders Somateria mollissima and a thresher shark Alopias vulpinus. Our results indicate that G. intestinalis is prevalent in marine ecosystems, and a wide range of marine hosts capable of harboring zoonotic forms of this parasite exist. The presence of G. intestinalis in marine ecosystems raises concerns about how this disease might be transmitted among different host species.


Oncologists' perspectives on adherence/non-adherence to adjuvant endocrine therapy and management strategies in women with breast cancer.
Adherence to adjuvant endocrine therapy (AET) is suboptimal, and a range of variables have been explored for understanding patients' experiences and motivations for medication-taking. However, oncologists' views on adherence are poorly understood. The aim of this study was to explore oncologists' perspectives on adherence/non-adherence and their strategies to ensure patients continue with treatments to inform the development of potential modifiable interventions. A qualitative study using in-depth, semi-structured interviews with 16 oncologists was conducted in Argentina. A stratified purposive sampling was used to recruit female and male participants from 3 health subsystems (private, social security, and public). Data were analyzed using the Framework approach. Oncologists believed patients' adherence was overall high and associated it with good tolerance of AET in comparison to chemotherapy, information provided, and patients feeling reassured (fear of recurrence). Non-adherence was not perceived as a major source of concern, and it was related to rare cases of severe side effects, young age, refusing treatment, losing the insurance plan, lack of education, and social circumstances. Patients' complaints of bothersome side effects were not identified as a main reason to discontinuation. Public and private sector patients, however, were perceived as having different attitudes toward side effects. Management strategies included medicine change, referral to support services, and a supportive relationship with the oncologist. Oncologists' perspectives on adherence/non-adherence to AET show similarities and significant differences with those in the literature based on patient-reported factors. Overall adherence was considered high, but the likelihood of unintentional non-adherence seems important in public sector patients. Information to patients should provide clear explanations on both severe and unpleasant side effects. Interventions to improve communication skills in oncologists and specialists responsible for survivorship care should be considered to strengthen patients' self-efficacy and effective medication-taking. Reliable data on adherence are needed.


Comparative evaluation of As, Se and V removal technologies for the treatment of oil refinery wastewater.
In this study, a broad range of readily deployable metal removal technologies were tested on a US refinery's wastewater to determine vanadium, arsenic and selenium removal performance. The bench-scale treatability studies were designed and performed so that test conditions could be as uniform as possible given the different mechanisms of action and engineering applications of each technology. The experimental data show that both ferric precipitation and reactive filtration were able to remove As, Se and V more efficiently from the wastewater than other tested technologies. Additionally, granular ferric hydroxide (GFH) adsorption was also effective in both V and As removal. Although the thiol-SAMMS adsorbent was developed for mercury removal, it also demonstrated appreciable selenium removal. None of the tested membrane filtration technologies showed any significant metals removal. This was attributed to the dissolved form of the metals as well as the wastewater's fouling characteristics.


Prevailing Clusters of Canine Behavioural Traits in Historical US Demand for Dog Breeds (1926⁻2005).
Drawing on American Kennel Club (AKC) puppy registration numbers for approximately 82 varieties of pedigree dogs between 1926 and 2005, the current article analyses behavioural reports on 32,005 dogs of these varieties reported through the Canine Behavioural Assessment and Research Questionnaire (C-BARQ). Cluster analysis of C-BARQ scores indicates that the 82 breeds fell into six clusters. Average scores for each of the 14 behavioural subscales and 22 miscellaneous traits in C-BARQ were calculated for each cluster, and the breeds in each cluster with average scores most similar to the cluster averages were selected as titular breeds. Titular breeds for each cluster were the Maltese terrier, the Great Dane, the Akita, the Australian shepherd, the American Staffordshire terrier, and the Weimaraner. Using the AKC data, we tracked longitudinal trends in annual registration numbers of breeds of each cluster over the period from 1926 to 2005. This period was subdivided into periods with differing overall trends by fitting natural cubic splines to the overall raw trend and considering both the spline and its derivative curves. Differences in the absolute numbers of dogs and trends in registrations over nearly 80 years were identified: an Early period (1926⁻1944, during which total registration numbers were very low); a Mid-Century Period (1945⁻1971, during which total registration numbers were tending to rise from year to year); a First Decline (1972⁻1979, a brief period during which registration numbers experienced a trend of more gradual decline); a Recovery (1980⁻1992, where registration numbers began to gradually rise again); and a Second Decline (1993⁻2005, a second sustained period of falling registration numbers, more dramatic than the first decline). The current article describes the ways in which the clustered behaviour of dogs associate with these trends. That said, there is no compelling evidence that shifts in the popularity within or between the clusters reflect consumer canine behavioural preferences. Understanding historic trends in the demand for certain canine behavioural traits could help veterinary and urban animal management stakeholders to anticipate future needs for education and infrastructure.


Randomised controlled trial of Lactobacillus rhamnosus (LGG) versus placebo in children presenting to the emergency department with acute gastroenteritis: the PECARN probiotic study protocol.
Acute gastroenteritis (AGE) is a common and burdensome condition that affects millions of children worldwide each year. Currently available strategies are limited to symptomatic management, treatment and prevention of dehydration and infection control; no disease-modifying interventions exist. Probiotics, defined as live microorganisms beneficial to the host, have shown promise in improving AGE outcomes, but existing studies have sufficient limitations such that the use of probiotics cannot currently be recommended with confidence. Here we present the methods of a large, rigorous, randomised, double-blind placebo-controlled study to assess the effectiveness and side effect profile of Lactobacillus rhamnosus GG (LGG) (ATCC 53103) in children with AGE. The study is being conducted in 10 US paediatric emergency departments (EDs) within the federally funded Pediatric Emergency Care Applied Research Network, in accordance with current SPIRIT and CONSORT statement recommendations. We will randomise 970 children presenting to participating EDs with AGE to either 5 days of treatment with LGG (1010colony-forming unit twice a day) or placebo between July 2014 to December 2017. The main outcome is the occurrence of moderate-to-severe disease over time, as defined by the Modified Vesikari Scale. We also record adverse events and side effects related to the intervention. We will conduct intention-to-treat analyses and use an enrichment design to restore the statistical power in case the presence of a subpopulation with a substantially low treatment effect is identified. Institutional review board approval has been obtained at all sites, and data and material use agreements have been established between the participating sites. The results of the trial will be published in peer-reviewed journals. A deidentified public data set will be made available after the completion of all study procedures. NCT01773967.


Mechanisms of head stability during gait initiation in young and older women: A neuro-mechanical analysis.
Decreased head stability has been reported in older women during locomotor transitions such as the initiation of gait. The aim of the study was to investigate the neuro-mechanical mechanisms underpinning head stabilisation in young and older women during gait initiation. Eleven young (23.1 ± 1.1 yrs) and 12 older (73.9 ± 2.4 yrs) women initiated walking at comfortable speed while focussing on a fixed visual target at eye level. A stereophotogrammetric system was used to assess variability of angular displacement and RMS acceleration of the pelvis, trunk and head, and dynamic stability in the anteroposterior and mediolateral directions. Latency of muscle activation in the sternocleidomastoid, and upper and lower trunk muscles were determined by surface electromyography. Older displayed higher variability of head angular displacement, and a decreased ability to attenuate accelerations from trunk to head, compared to young in the anteroposterior but not mediolateral direction. Moreover, older displayed a delayed onset of sternocleidomastoid activation than young. In conclusion, the age-related decrease in head stability could be attributed to an impaired ability to attenuate accelerations from trunk to head along with delayed onset of neck muscles activation.


The Grapevine and Wine Microbiome: Insights from High-Throughput Amplicon Sequencing.
From the time when microbial activity in wine fermentation was first demonstrated, the microbial ecology of the vineyard, grape, and wine has been extensively investigated using culture-based methods. However, the last 2 decades have been characterized by an important change in the approaches used for microbial examination, due to the introduction of DNA-based community fingerprinting methods such as DGGE, SSCP, T-RFLP, and ARISA. These approaches allowed for the exploration of microbial community structures without the need to cultivate, and have been extensively applied to decipher the microbial populations associated with the grapevine as well as the microbial dynamics throughout grape berry ripening and wine fermentation. These techniques are well-established for the rapid more sensitive profiling of microbial communities; however, they often do not provide direct taxonomic information and possess limited ability to detect the presence of rare taxa and taxa with low abundance. Consequently, the past 5 years have seen an upsurge in the application of high-throughput sequencing methods for the in-depth assessment of the grapevine and wine microbiome. Although a relatively new approach in wine sciences, these methods reveal a considerably greater diversity than previously reported, and identified several species that had not yet been reported. The aim of the current review is to highlight the contribution of high-throughput next generation sequencing and metagenomics approaches to vineyard microbial ecology especially unraveling the influence of vineyard management practices on microbial diversity.


Relationship between dietary phytoestrogens and development of urinary incontinence in midlife women.
Because exogenous estrogen treatment has been associated with a higher risk of urinary incontinence, our objective was to evaluate the longitudinal relationships of dietary phytoestrogen intakes (isoflavones, coumestans, and lignans) and the development of incontinence in midlife women transitioning through menopause. The Study of Women's Health Across the Nation (SWAN) Phytoestrogen Study was developed within SWAN, a community-based, multisite, multiracial/ethnic, prospective cohort study. SWAN interviewers administered a food consumption assessment at baseline and on follow-up visits 5 and 9. The SWAN Phytoestrogen Study created a phytonutrient database that allowed estimation of the usual daily intakes of four isoflavones, four lignans, and coumestrol. On an annual self-administered questionnaire, participants reported on the frequency and type of incontinence. We used discrete proportional hazards models to evaluate whether the estimated daily intake of each phytoestrogen class on the visit previous to the first report of incontinence was associated with the development of monthly or more incontinence versus remaining continent. We found no association or patterns of association between developing any, stress, or urge incontinence and the reported daily dietary intake of isoflavones, coumestrol, and lignans on the visit previous to the onset of incontinence. The results of this longitudinal study provide important information to better understand estrogenlike substances in the continence mechanism of midlife women. Our study shows that neither high nor low dietary intakes of isoflavones, coumestrol, and lignans prevent stress or urge incontinence. Future studies should evaluate whether serum levels of phytoestrogens or their metabolites impact incontinence symptoms.


Social support and the development of immune function in human immunodeficiency virus infection.
A psychosocial investigation offered to all human immunodeficiency virus (HIV)-infected men with moderately severe or severe hemophilia in Sweden was made in 1986. Most of these men had been infected in the years 1980 to 1984 and told about their infections in 1985. Forty-nine subjects had answered questions in regard to sources of emotional support in their life situation. Based on the responses to these questions a score of "availability of attachment" (AVAT) was calculated, and two groups of patients were identified: one with high AVAT and one with low AVAT scores. The subjects were followed with regard to the state of their immune system, as reflected by CD4 counts, until 1990. The results indicated that a low AVAT score in 1985 was associated with a significantly more rapid progressive deterioration in CD4 count during subsequent years. The mechanism behind this association is unknown. Several possible confounders were not studied. However, if the association between a poor AVAT score and rapid CD4 deterioration after HIV infection is replicated in other samples, it could be important to the future clinical care of HIV-infected subjects.


Human alveolar macrophages produce a fibroblast-like collagenase and collagenase inhibitor.
Human macrophages have been implicated in connective tissue remodeling; however, little is known about their direct effects upon collagen degradation. We now report that human alveolar macrophages in culture produced both a collagenase and a collagenase inhibitor. The collagenase was secreted in latent form and could be activated by exposure to trypsin. Collagenase production could be increased three- to fourfold by incubating the cells with lipopolysaccharide, but synthesis was largely unaffected by exposure to phorbol myristate acetate. By several criteria, macrophage collagenase was the same as the collagenase secreted by human skin fibroblasts: (a) they were antigenically indistinguishable in double immunodiffusion; (b) both degraded type III collagen preferentially to type I, had little activity against type II collagen, and none against types IV and V, and (c) their affinity for susceptible collagens was equivalent, Michaelis constant = 1-2 microM. Collagenase inhibitory activity was also present in the macrophage-conditioned medium, and was accounted for by an antigen that showed immunologic and functional identity with the collagenase inhibitor secreted by human skin fibroblasts. The amount of inhibitor released by unstimulated cells, approximately 100 ng/10(6) cells per 24 h, was substantially augmented by both phorbol and lipopolysaccharide, although considerable variability in response to these agents was observed between macrophage populations derived from different subjects. As negligible quantities of collagenase or collagenase inhibitor were detectable intracellularly, it appeared that both proteins were secreted rapidly after synthesis. Thus, human macrophages have the capacity to modulate collagen degradation directly by production of collagenase and collagenase inhibitor.


The Ratio of Exhausted to Resident Infiltrating Lymphocytes Is Prognostic for Colorectal Cancer Patient Outcome.
Immunotherapy success in colorectal cancer is mainly limited to patients whose tumors exhibit high microsatellite instability (MSI). However, there is variability in treatment outcomes within this group, which is in part driven by the frequency and characteristics of tumor-infiltrating immune cells. Indeed, the presence of specific infiltrating immune-cell subsets has been shown to correlate with immunotherapy response and is in many cases prognostic of treatment outcome. Tumor-infiltrating lymphocytes (TIL) can undergo distinct differentiation programs, acquiring features of tissue-residency or exhaustion, a process during which T cells upregulate inhibitory receptors, such as PD-1, and lose functionality. Although residency and exhaustion programs of CD8+ T cells are relatively well studied, these programs have only recently been appreciated in CD4+ T cells and remain largely unknown in tumor-infiltrating natural killer (NK) cells. In this study, we used single-cell RNA sequencing (RNA-seq) data to identify signatures of residency and exhaustion in colorectal cancer-infiltrating lymphocytes, including CD8+, CD4+, and NK cells. We then tested these signatures in independent single-cell data from tumor and normal tissue-infiltrating immune cells. Furthermore, we used versions of these signatures designed for bulk RNA-seq data to explore tumor-intrinsic mutations associated with residency and exhaustion from TCGA data. Finally, using two independent transcriptomic datasets from patients with colon adenocarcinoma, we showed that combinations of these signatures, in particular combinations of NK-cell activity signatures, together with tumor-associated signatures, such as TGFβ signaling, were associated with distinct survival outcomes in patients with colon adenocarcinoma.


Looking 'the same': experiences of women who have had corrective surgery for breast asymmetry.
Qualitative interviews with ten women found that following corrective surgery for congenital breast asymmetry, women were still concerned with the symmetry of their breasts and expressed high ideals regarding symmetry. Although women found an improvement in body confidence, some felt their confidence and socializing would be further improved with time. Women were secretive about their breast asymmetry and their surgery, being fearful of negative reactions from other people. It is necessary to establish and improve patients' expectations of the outcome of surgery particularly regarding symmetry, as well as providing psychological and social support to women after surgery.