To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Online self-reported 24-h dietary recall systems promise increased feasibility of dietary assessment. Comparison against interviewer-led recalls established their convergent validity; however, reliability and criterion-validity information is lacking. The validity of energy intakes (EI) reported using Intake24, an online 24-h recall system, was assessed against concurrent measurement of total energy expenditure (TEE) using doubly labelled water in ninety-eight UK adults (40–65 years). Accuracy and precision of EI were assessed using correlation and Bland–Altman analysis. Test–retest reliability of energy and nutrient intakes was assessed using data from three further UK studies where participants (11–88 years) completed Intake24 at least four times; reliability was assessed using intra-class correlations (ICC). Compared with TEE, participants under-reported EI by 25 % (95 % limits of agreement −73 % to +68 %) in the first recall, 22 % (−61 % to +41 %) for average of first two, and 25 % (−60 % to +28 %) for first three recalls. Correlations between EI and TEE were 0·31 (first), 0·47 (first two) and 0·39 (first three recalls), respectively. ICC for a single recall was 0·35 for EI and ranged from 0·31 for Fe to 0·43 for non-milk extrinsic sugars (NMES). Considering pairs of recalls (first two v. third and fourth recalls), ICC was 0·52 for EI and ranged from 0·37 for fat to 0·63 for NMES. EI reported with Intake24 was moderately correlated with objectively measured TEE and underestimated on average to the same extent as seen with interviewer-led 24-h recalls and estimated weight food diaries. Online 24-h recall systems may offer low-cost, low-burden alternatives for collecting dietary information.
We read with interest the recent editorial, “The Hennepin Ketamine Study,” by Dr. Samuel Stratton commenting on the research ethics, methodology, and the current public controversy surrounding this study.1 As researchers and investigators of this study, we strongly agree that prospective clinical research in the prehospital environment is necessary to advance the science of Emergency Medical Services (EMS) and emergency medicine. We also agree that accomplishing this is challenging as the prehospital environment often encounters patient populations who cannot provide meaningful informed consent due to their emergent conditions. To ensure that fellow emergency medicine researchers understand the facts of our work so they may plan future studies, and to address some of the questions and concerns in Dr. Stratton’s editorial, the lay press, and in social media,2 we would like to call attention to some inaccuracies in Dr. Stratton’s editorial, and to the lay media stories on which it appears to be based.
Ho JD, Cole JB, Klein LR, Olives TD, Driver BE, Moore JC, Nystrom PC, Arens AM, Simpson NS, Hick JL, Chavez RA, Lynch WL, Miner JR. The Hennepin Ketamine Study investigators’ reply. Prehosp Disaster Med. 2019;34(2):111–113
We assessed whether paternal demographic, anthropometric and clinical factors influence the risk of an infant being born large-for-gestational-age (LGA). We examined the data on 3659 fathers of term offspring (including 662 LGA infants) born to primiparous women from Screening for Pregnancy Endpoints (SCOPE). LGA was defined as birth weight >90th centile as per INTERGROWTH 21st standards, with reference group being infants ⩽90th centile. Associations between paternal factors and likelihood of an LGA infant were examined using univariable and multivariable models. Men who fathered LGA babies were 180 g heavier at birth (P<0.001) and were more likely to have been born macrosomic (P<0.001) than those whose infants were not LGA. Fathers of LGA infants were 2.1 cm taller (P<0.001), 2.8 kg heavier (P<0.001) and had similar body mass index (BMI). In multivariable models, increasing paternal birth weight and height were independently associated with greater odds of having an LGA infant, irrespective of maternal factors. One unit increase in paternal BMI was associated with 2.9% greater odds of having an LGA boy but not girl; however, this association disappeared after adjustment for maternal BMI. There were no associations between paternal demographic factors or clinical history and infant LGA. In conclusion, fathers who were heavier at birth and were taller were more likely to have an LGA infant, but maternal BMI had a dominant influence on LGA.
The aim of this study was to estimate the effectiveness of first-line biologic disease modifying drugs(boDMARDs), and their approved biosimilars (bsDMARDs), compared with conventional (csDMARD) treatment, in terms of ACR (American College of Rheumatology) and EULAR (European League against Rheumatism) responses.
Systematic literature search, on eight databases to January 2017, sought ACR and EULAR data from randomized controlled trials (RCTs) of boDMARDs / bsDMARDs (in combination with csDMARDs, or monotherapy). Two adult populations: methotrexate (MTX)-naïve patients with severe active RA; and csDMARD-experienced patients with moderate-to-severe active RA. Network meta-analyses (NMA) were conducted using a Bayesian Markov chain Monte Carlo simulation using a random effects model with a probit link function for ordered categorical.
Forty-six RCTs met the eligibility criteria. In the MTX-naïve severe active RA population, no biosimilar trials meeting the inclusion criteria were identified. MTX plus methylprednisolone (MP) was most likely to achieve the best ACR response. There was insufficient evidence that combination boDMARDs was superior to intensive (two or more) csDMARDs. In the csDMARD-experienced, moderate-to-severe RA population, the greatest effects for ACR responses were associated with tocilizumab (TCZ) monotherapy, and combination therapy (plus MTX) with bsDMARD etanercept (ETN) SB4, boDMARD ETN and TCZ. These treatments also had the greatest effects on EULAR responses. No clear differences were found between the boDMARDs and their bsDMARDs.
In MTX-naïve patients, there was insufficient evidence that combination boDMARDs was superior to two or more csDMARDs. In csDMARD-experienced patients, boDMARDs and bsDMARDs were comparable and all combination boDMARDs / bsDMARDs were superior to single csDMARD.
SNP in the vitamin D receptor (VDR) gene is associated with risk of lower respiratory infections. The influence of genetic variation in the vitamin D pathway resulting in susceptibility to upper respiratory infections (URI) has not been investigated. We evaluated the influence of thirty-three SNP in eleven vitamin D pathway genes (DBP, DHCR7, RXRA, CYP2R1, CYP27B1, CYP24A1, CYP3A4, CYP27A1, LRP2, CUBN and VDR) resulting in URI risk in 725 adults in London, UK, using an additive model with adjustment for potential confounders and correction for multiple comparisons. Significant associations in this cohort were investigated in a validation cohort of 737 children in Manchester, UK. In all, three SNP in VDR (rs4334089, rs11568820 and rs7970314) and one SNP in CYP3A4 (rs2740574) were associated with risk of URI in the discovery cohort after adjusting for potential confounders and correcting for multiple comparisons (adjusted incidence rate ratio per additional minor allele ≥1·15, Pfor trend ≤0·030). This association was replicated for rs4334089 in the validation cohort (Pfor trend=0·048) but not for rs11568820, rs7970314 or rs2740574. Carriage of the minor allele of the rs4334089 SNP in VDR was associated with increased susceptibility to URI in children and adult cohorts in the United Kingdom.
Enlist E3™ soybean, resistant to 2,4-D, glufosinate, and glyphosate, provides options to control glyphosate-resistant Sumatran fleabane before planting and in crop. Twenty field trials were conducted in Argentina to determine Enlist E3 soybean sensitivity to POST applications of 2,4-D choline+glyphosate or glufosinate. Maximum injury from a single 2,4-D choline+glyphosate application at 1X (1140+1140 g ae ha−1) and 2X rate was 4% and 13%, respectively, at 3 days after treatment in the temperate Humid Pampa region. Slightly higher injury of 11 and 23% was observed in sub-tropical region of northern Argentina. Injury was transient with recovery occurring within 14 days. Injury caused by sequential applications was equivalent to that caused by single applications. Soybean yield was not affected by single nor sequential applications. In four trials, control programs containing 2,4-D choline+glyphosate applied PRE and POST provided greater GR Sumatran fleabane control and a 12 to 26% increase in yield compared to 2,4-D choline+glyphosate applied at PRE only. This research demonstrates the glyphosate-resistant control programs that include 2,4-D choline, glyphosate, and glufosinate provide excellent GR Sumatran fleabane control.
Access to transition-related medical interventions (TRMIs) for transgender veterans has been the subject of substantial public interest and debate. To better inform these important conversations, the current study investigated whether undergoing hormone or surgical transition intervention(s) relates to the frequency of recent suicidal ideation (SI) and symptoms of depression in transgender veterans.
This study included a cross-sectional, national sample of 206 self-identified transgender veterans. They self-reported basic demographics, TRMI history, recent SI, and symptoms of depression through an online survey.
Significantly lower levels of SI experienced in the past year and 2-weeks were seen in veterans with a history of both hormone intervention and surgery on both the chest and genitals in comparison with those who endorsed a history of no medical intervention, history of hormone therapy but no surgical intervention, and those with a history of hormone therapy and surgery on either (but not both) the chest or genitals when controlling for sample demographics (e.g., gender identity and annual income). Indirect effect analyses indicated that lower depressive symptoms experienced in the last 2-weeks mediated the relationship between the history of surgery on both chest and genitals and SI in the last 2-weeks.
Results indicate the potential protective effect that TRMI may have on symptoms of depression and SI in transgender veterans, particularly when both genitals and chest are affirmed with one's gender identity. Implications for policymakers, providers, and researchers are discussed.
To illuminate which features of an unpredictable environment early in life best forecast adolescent and adult functioning, data from two longitudinal studies were examined. After decomposing a composite unpredictability construct found to predict later development, results of both studies revealed that paternal transitions predicted outcomes more consistently and strongly than did residential or occupational changes across the first 5 years of a child's life. These results derive from analyses of the NICHD Study of Early Child Care and Youth Development, which included diverse families from 10 different sites in the United States, and from the Minnesota Longitudinal Study of Risk and Adaptation, whose participants came from one site, were disproportionately economically disadvantaged, and were enrolled 15 years earlier than the NICHD Study sample. The finding that results from both studies are consistent with evolutionary, life history thinking regarding the importance of males in children's lives makes this general, cross-study replication noteworthy.
Aqueous two-phase systems and related emulsion-based structures defined within micro- and nanoscale environments enable a bottom-up synthetic biological approach to mimicking the dynamic compartmentation of biomaterial that naturally occurs within cells. Model systems we have developed to aid in understanding these phenomena include on-demand generation and triggering of reversible phase transitions in ATPS confined in microscale droplets, morpho-logical changes in networks of femtoliter-volume aqueous droplet interface bilayers (DIBs) formulated in microfluidic channels, and temperature-driven phase transitions in interfacial lipid bilayer systems supported on micro and nanostructured substrates. For each of these cases, the dynamics were intimately linked to changes in the chemical potential of water, which becomes increasingly susceptible to confinement and crowding. At these length scales, where interfacial and surface areas predominate over compartment volumes, both evaporation and osmotic forces become enhanced relative to ideal dilute solutions. Consequences of confinement and crowding in cell-sized microcompartments for increasingly complex scenarios will be discussed, from single-molecule mobility measurements with fluorescence correlation spectroscopy to spatio-temporal modulation of resource sharing in cell-free gene expression bursting.
In 2011, 14 Midwest trial locations evaluated tolerance of an AAD-1 and glyphosate-resistant corn hybrid to a 2,4-D choline+glyphosate premix formulation applied single and sequential POST at V4 and/or V7 corn with and without a PRE application of 2,4-D dimethylamine (DMA). Herbicides were applied at 1X and 2X maximum use rates with 1X rates of 1120 g ae ha−1 for glyphosate and 2,4-D DMA and 1065+1120 g ae ha−1 for the 2,4-D choline+glyphosate premix, respectively. Crop response was greatest 2 d after 2X rate applications, resulting in 4 to 10% visible injury to corn across application timings. No brace root injury or effect on corn grain yield were observed.
The purpose of this study was to evaluate a programme of lesion surgery carried out on patients with treatment-resistant depression (TRD).
This was a retrospective study looking at clinical and psychometric data from 45 patients with TRD who had undergone bilateral stereotactic anterior capsulotomy surgery over a period of 15 years, with the approval of the Mental Health Act Commission (37 with unipolar depression and eight with bipolar disorder). The Beck Depression Inventory (BDI) before and after surgery was used as the primary outcome measure. The Montgomery–Asberg Depression Rating Scale was administered and cognitive aspects of executive and memory functions were also examined. We carried out a paired-samples t test on the outcome measures to determine any statistically significant change in the group as a consequence of surgery.
Patients improved on the clinical measure of depression after surgery by −21.20 points on the BDI with a 52% change. There were no significant cognitive changes post-surgery. Six patients were followed up in 2013 by phone interview and reported a generally positive experience. No major surgical complications occurred.
With the limitations of an uncontrolled, observational study, our data suggest that capsulotomy can be an effective treatment for otherwise TRD. Performance on neuropsychological tests did not deteriorate.
One salient characteristic of twin studies and the related behavioral genetics paradigm is the requirement of a large sample size. Countries or regions that are large in size and highly populated are at an advantage when implementing twin studies. However, given the fascinating and promising results obtained from twin studies, many researchers based in smaller countries or regions may still want to conduct twin studies in order to address local and theoretical issues. In this article, we have outlined the development of twin studies in Hong Kong, one of the Special Administrative Regions of China. The historical development and design of the two major twin studies of language and reading development implemented within Hong Kong are discussed, providing insights to researchers who also aspire to conduct twin studies in small regions.
Hearing loss can impair effective communication between caregivers and individuals with cognitive impairment. However, hearing loss is not often measured or addressed in care plans for these individuals. The aim of this study is to measure the prevalence of hearing loss and the utilization of hearing aids in a sample of individuals with cognitive impairment in a tertiary care memory clinic.
A retrospective review of 133 charts of individuals >50 years who underwent hearing assessment at a tertiary care memory clinic over a 12-month period (June 2014–June 2015) was undertaken. Using descriptive statistics, the prevalence of hearing loss was determined and associations with demographic variables, relevant medical history, cognitive status, and hearing aid utilization were investigated.
Results indicate that hearing loss is highly prevalent among this sample of cognitively impaired older adults. Sixty percent of the sample had at least a mild hearing loss in the better hearing ear. Among variables examined, age, MMSE, and medical history of diabetes were strongly associated with hearing impairment. Hearing aid utilization increased in concordance with severity of hearing loss, from 9% to 54% of individuals with a mild or moderate/severe hearing loss, respectively.
Hearing loss is highly prevalent among older adults with cognitive impairment. Despite high prevalence of hearing loss, hearing aid utilization remains low. Our study highlights the importance of hearing evaluation and rehabilitation as part of the cognitive assessment and care management plan in this vulnerable population.
Hemostasis is a complex process and is difficult to monitor in its entirety. Many laboratory tests have been developed to discern specific parts of the coagulation process in an attempt to diagnose disorders such as a tendency toward bleeding or clotting abnormally, and/or to predict clinical outcomes in these disorders. Because an in vitro test is simply a model of an in vivo process, it is important to understand what each test is measuring and its limitations. Traditional clotting assays such as the prothrombin time (PT) and activated partial thromboplastin time (APTT) measure the time for initiation of clot formation when, following initiation of coagulation in plasma via differing activators (PT: “thromboplastin,” comprised of tissue factor and phospholipid; APTT: “partial thromboplastin,” comprised of phospholipid without tissue factor), thrombin mediates the conversion of fibrinogen to fibrin. The endpoint of the PT and APTT occurs when only approximately 5% of thrombin has been produced . PT and APTT also do not provide information regarding the rate and extent of clot formation, nor lytic function. As for other global tests, they are non-specific assays and, for abnormal test results, further testing is generally warranted to evaluate causality. Specific testing may include factor assays to evaluate for a factor deficiency or antibody testing to assess for inhibitory antibodies. The need for improved testing of hemostasis has been long recognized but an accepted standardized test is not yet widely available.
Thrombophilic states and the propensity toward thrombosis are difficult to diagnose/predict with laboratory assays. Testing for thrombophilia can be cumbersome, generally requiring testing for individual abnormalities, and may be difficult with smaller patients due to the amount of blood required for comprehensive testing. There is a need for improved thrombophilia/thrombosis testing and monitoring. Global assays attempt to better define the complete course of clot formation and breakdown through avenues such as the measurement of thrombin generation, fibrin formation, plasmin generation, and clot dissolution. Through a more complete picture of the hemostatic process, global assays may fill the gaps in knowledge regarding hemostatic abnormalities.
The Enlightenment took enormous interest in a wide variety of religious topics: the existence of God, the problem of evil, the meaning of revelation, ecclesiastical authority, the status of scripture, religious tolerance, and immortality. This last issue is particularly important as one of the essential components, along with the existence of a moral God, of a “natural” theology that could be fully derived or endorsed by reason. Furthermore, reflection on immortality plays directly into the urgent discussions in the eighteenth century about autonomy, freedom, and progress; the way one envisions a hereafter profoundly reflects and legitimates the way one envisions life in the present. This fluidity between an understanding of the here and the hereafter is perfectly captured in Johann Joachim Spalding's extremely influential Bestimmung des Menschen (1748; The Vocation of Man), which envisions immortality as a process of ever increasing rational pleasure and self-perfection—goals not at all unfamiliar to the mortals of the Enlightenment.
Johann Gottfried Herder is a central and in some ways transitional voice in this public discussion of man's immortal Bestimmung. In the early 1769 letters to Mendelssohn he espoused a model of nonprogressive palingenesis, in which the soul is endlessly reborn within the same class of being without undergoing any overarching development. There is, in short, no personal, angelic afterlife. Compared to the essentially Christian afterlife of the rationalist Popularphilosophen of Herder's day, this position was quite austere.
“Classicism” and “secular humanism” seems an obvious combination: Goethe, the great pagan, substituted a generalized ethic of humanity (taken in its broadest possible religio-ethical and aesthetic sense) as the social glue that replaced the function of sectarian religion in post-Enlightenment secularized Europe. He offered a heightened version of Enlightenment culture and reason that obviated the need for religion. Through World War I his name alone evoked an entire system of ethics, aesthetics, and even epistemology among writers as disparate as Adalbert Stifter, Wilhelm Raabe, Theodor Fontane, Hugo von Hofmannsthal; and scholars such as the psychoanalytic generation, Hannah Arendt, Norbert Elias, Oswald Spengler; and philosophers such as Benedetto Croce and José Ortega y Gasset. My subtitle reveals the underlying schism— “sanctification” is a religious term; Die Zauberflöte (The Magic Flute), a hangover of the particularly secular and disrespectful Enlightenment associated with the French Revolution; and the “Novelle,” a charming, respectable, Biedermeier idyll. The Goethe cult that substituted German classicism for religion was, for better or worse, not interested in the Goethe of the 1820s, except for his conversations with Eckermann; “the late Goethe,” or, as I would have it, “the Biedermeier Goethe,” offers, however, a more mature, richer classicism, indeed a sanctified classicism.