We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save 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 saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
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 saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved 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.
Objectives/Goals: Imaging neuromas, benign tumors of nerve tissue, can be difficult in amputees with osseointegrated (OI) prostheses, in which a metal rod is implanted into the residual limb. Magnetic resonance imaging can be inadequate due to the implanted metal. The aim of this study is to assess the use of ultrasound to detect neuromas in patients with OI prostheses. Methods/Study Population: This is a single-institutional observational study of 7 patients undergoing lower limb OI prostheses. Lower extremity nerve ultrasounds with 2-D grayscale and Doppler were completed at postoperative follow-up visits following OI prosthesis implantation. Specifically, the sciatic nerve, tibial nerve, common peroneal nerve, and sural nerve were targeted for imaging. Neuromas found on ultrasound were measured by maximal length in three planes. Results/Anticipated Results: Our study to date includes two patients with OI prostheses. The remaining patients will be accrued by the end of December. The first patient with a left below-the-knee amputation completed imaging 3 years after OI prosthesis implantation. The common peroneal nerve showed preserved fascicular architecture and morphology, with no distinct neuroma formation. However, the sural nerve demonstrated a 6 × 5 × 4 mm neuroma with minimal pain with deep palpation. The tibial nerve demonstrated a 14 × 11 × 8 mm neuroma within the medial calf musculature, with mild pain with deep palpation. The second patient with a right above-the-knee amputation was imaged 10 months after OI prosthesis implantation. The sciatic nerve demonstrated preserved fascicular morphology and terminated in a smooth taper. There was no defined neuroma. Discussion/Significance of Impact: In conclusion, we have preliminarily shown in the first two patients that ultrasound can successfully image neuromas in patients with OI prostheses in the postoperative period. Furthermore, despite a patient that was 3 years postoperative with two neuromas, the neuromas produced minimal to mild pain with targeted palpation.
Bilinguals use languages strategically and make decisions differently depending on the language context. Here, we explored whether verbal feedback modulates language use and risk-taking in bilinguals engaged in a coin-drawing game that incentivises lying. In the game, participants announced bets in Chinese or English, and feedback on the outcome of the current bet was given in the same language. They selected Chinese over English after receiving positive feedback in Chinese, and no language difference was found when feedback was provided in English. They also tended to take more risks after receiving positive than negative feedback. Furthermore, participants were more likely to switch from one language to the other following negative feedback as compared to positive feedback, and when telling the truth, they were faster after negative than positive feedback. Thus, the language in which bilinguals receive feedback constrains language use, which may have implications for understanding interactions in multilingual communities.
Edited by
Paul A. Banaszkiewicz, Queen Elizabeth Hospital and North East NHS Surgical Centre (NENSC), Gateshead,Kiran Singisetti, Queen Elizabeth Hospital, Gateshead Health NHS Foundation Trust
This will guide a candidate in the hip questions and topics that regularly appear in Section 1 of the FRCS(Tr&Orth) exam. Up to date information, higher order SBA questions and detailed explanations along with an evidence based approach to the most appropriate answer.
Educational attainment (EduA) is correlated with life outcomes, and EduA itself is influenced by both cognitive and non-cognitive factors. A recent study performed a ‘genome-wide association study (GWAS) by subtraction,’ subtracting genetic effects for cognitive performance from an educational attainment GWAS to create orthogonal ‘cognitive’ and ‘non-cognitive’ factors. These cognitive and non-cognitive factors showed associations with behavioral health outcomes in adults; however, whether these correlations are present during childhood is unclear.
Methods
Using data from up to 5517 youth (ages 9–11) of European ancestry from the ongoing Adolescent Brain Cognitive DevelopmentSM Study, we examined associations between polygenic scores (PGS) for cognitive and non-cognitive factors and cognition, risk tolerance, decision-making & personality, substance initiation, psychopathology, and brain structure (e.g. volume, fractional anisotropy [FA]). Within-sibling analyses estimated whether observed genetic associations may be consistent with direct genetic effects.
Results
Both PGSs were associated with greater cognition and lower impulsivity, drive, and severity of psychotic-like experiences. The cognitive PGS was also associated with greater risk tolerance, increased odds of choosing delayed reward, and decreased likelihood of ADHD and bipolar disorder; the non-cognitive PGS was associated with lack of perseverance and reward responsiveness. Cognitive PGS were more strongly associated with larger regional cortical volumes; non-cognitive PGS were more strongly associated with higher FA. All associations were characterized by small effects.
Conclusions
While the small sizes of these associations suggest that they are not effective for prediction within individuals, cognitive and non-cognitive PGS show unique associations with phenotypes in childhood at the population level.
Although food insecurity affects a significant proportion of young children in New Zealand (NZ)(1), evidence of its association with dietary intake and sociodemographic characteristics in this population is lacking. This study aims to assess the household food security status of young NZ children and its association with energy and nutrient intake and sociodemographic factors. This study included 289 caregiver and child (1-3 years old) dyads from the same household in either Auckland, Wellington, or Dunedin, NZ. Household food security status was determined using a validated and NZ-specific eight-item questionnaire(2). Usual dietary intake was determined from two 24-hour food recalls, using the multiple source method(3). The prevalence of inadequate nutrient intake was assessed using the Estimated Average Requirement (EAR) cut-point method and full probability approach. Sociodemographic factors (i.e., socioeconomic status, ethnicity, caregiver education, employment status, household size and structure) were collected from questionnaires. Linear regression models were used to estimate associations with statistical significance set at p <0.05. Over 30% of participants had experienced food insecurity in the past 12 months. Of all eight indicator statements, “the variety of foods we are able to eat is limited by a lack of money,” had the highest proportion of participants responding “often” or “sometimes” (35.8%). Moderately food insecure children exhibited higher fat and saturated fat intakes, consuming 3.0 (0.2, 5.8) g/day more fat, and 2.0 (0.6, 3.5) g/day more saturated fat compared to food secure children (p<0.05). Severely food insecure children had lower g/kg/day protein intake compared to food secure children (p<0.05). In comparison to food secure children, moderately and severely food insecure children had lower fibre intake, consuming 1.6 (2.8, 0.3) g/day and 2.6 (4.0, 1.2) g/day less fibre, respectively. Severely food insecure children had the highest prevalence of inadequate calcium (7.0%) and vitamin C (9.3%) intakes, compared with food secure children [prevalence of inadequate intakes: calcium (2.3%) and vitamin C (2.8%)]. Household food insecurity was more common in those of Māori or Pacific ethnicity; living in areas of high deprivation; having a caregiver who was younger, not in paid employment, or had low educational attainment; living with ≥2 other children in the household; and living in a sole-parent household. Food insecure young NZ children consume a diet that exhibits lower nutritional quality in certain measures compared to their food-secure counterparts. Food insecurity was associated with various sociodemographic factors that are closely linked with poverty or low income. As such, there is an urgent need for poverty mitigation initiatives to safeguard vulnerable young children from the adverse consequences of food insecurity.
INDUCT (Interdisciplinary Network for Dementia Using Current Technology), and DISTINCT (Dementia Inter-sectorial strategy for training and innovation network for current technology) are two Marie Sklodowska-Curie funded International Training Networks that aimed to develop a multi-disciplinary, inter-sectorial educational research framework for Europe to improve technology and care for people with dementia, and to provide the evidence to show how technology can improve the lives of people with dementia.
Methods:
In INDUCT (2016-2020) 15 Early Stage Researchers worked on projects in the areas of Technology to support everyday life; technology to promote meaningful activities; and healthcare technology. In DISTINCT (2019-2023) 15 Early Stage Researchers worked on technology to promote Social health in three domains: fulfilling ones potential and obligations in society, managing one’s own life, and participation in social and other meaningful activities.
Both networks adopted three transversal objectives: 1) To determine practical, cognitive and social factors needed to make technology more useable for people with dementia; 2) To evaluate the effectiveness of specific contemporary technology; 3) To trace facilitators and barriers for implementation of technology in dementia care.
Results:
The main recommendations resulting from all research projects are integrated in a web-based digital Best Practice Guidance on Human Interaction with Technology in Dementia which was recently updated (Dec 2022 and June 2023) and will be presented at the congress. The recommendations are meant for different target groups, i.e. people in different stages of dementia, their (in)formal carers, policy makers, designers and researchers, who can easily find the recommendations relevant to them in the Best Practice Guidance by means of a digital selection tool.
Conclusions:
The INDUCT/DISTINCT Best Practice Guidance informs on how to improve the development, usage, impact and implementation of technology for people with dementia in various technology areas. This Best Practice Guidance is the result of intensive collaborative partnership of INDUCT and DISTINCT with academic and non-academic partners as well as the involvement of representatives of the different target groups throughout the projects.
Bacteria play an important role in determining the properties and behavior of clay minerals in natural environments and such interactions have great potential for creating stable biofilms and carbon storage sites in soils, but our knowledge of these interactions are far from complete. The purpose of this study was to understand better the effects of bacteria-generated biofilms on clay interlayer expansion. Mixtures of a colloidal, 2-water hectorite clay and Pseudomonas syringae in a minimal media suspension evolve into a polysaccharide-rich biofilm aggregate in time-series experiments lasting up to 1 week. X-ray diffraction analysis reveals that upon aggregation, the clay undergoes an initial interlayer contraction. Short-duration experiments, up to 72 h, result in a decrease in the d001 value from 1.50 to 1.26 nm. The initial interlayer contraction is followed in long-duration (up to 1 week) experiments by an expansion of the d001 value of 1.84 nm. The expansion is probably a result of large, biofilm-produced, polymeric molecules being emplaced in the interlayer site. The resultant organo-clay could provide a possible storage medium for carbon in a microbial colony setting.
OBJECTIVES/GOALS: The goal of this study was to develop a clinically applicable technique to increase the precision of in vivo dose monitoring during radiation therapy by mapping the dose deposition and resolving the temporal dose accumulation while the treatment is being delivered in real time. METHODS/STUDY POPULATION: Ironizing radiation acoustic imaging (iRAI) is a novel imaging concept with the potential to map the delivered radiation dose on anatomic structure in real time during external beam radiation therapy without interrupting the clinical workflow. The iRAI system consisted of a custom-designed two-dimensional (2D) matrix transducer array with integrated preamplifier array, driven by a clinic-ready ultrasound imaging platform. The feasibility of iRAI volumetric imaging in mapping dose delivery and real-time monitoring of temporal dose accumulation in a clinical treatment plan were investigated with a phantom, a rabbit model, and a cancer patient. RESULTS/ANTICIPATED RESULTS: The total dose deposition and temporal dose accumulation in 3D space of a clinical C-shape treatment plan in a targeted region were first imaged and optimized in a phantom. Then, semi-quantitative iRAI measurements were achieved in an in vivo rabbit model. Finally, for the first time, real-time visualization of radiation dose delivered deep in a patient with liver metastases was performed with a clinical linear accelerator. These studies demonstrate the potential of iRAI to monitor and quantify the radiation dose deposition during treatment. DISCUSSION/SIGNIFICANCE: Described here is the pioneering role of an iRAI system in mapping the 3D radiation dose deposition of a complex clinical radiotherapy treatment plan. iRAI offers a cost-effective and practical solution for real-time visualization of 3D radiation dose delivery, potentially leading to personalized radiotherapy with optimal efficacy and safety.
Optimizing research on the developmental origins of health and disease (DOHaD) involves implementing initiatives maximizing the use of the available cohort study data; achieving sufficient statistical power to support subgroup analysis; and using participant data presenting adequate follow-up and exposure heterogeneity. It also involves being able to undertake comparison, cross-validation, or replication across data sets. To answer these requirements, cohort study data need to be findable, accessible, interoperable, and reusable (FAIR), and more particularly, it often needs to be harmonized. Harmonization is required to achieve or improve comparability of the putatively equivalent measures collected by different studies on different individuals. Although the characteristics of the research initiatives generating and using harmonized data vary extensively, all are confronted by similar issues. Having to collate, understand, process, host, and co-analyze data from individual cohort studies is particularly challenging. The scientific success and timely management of projects can be facilitated by an ensemble of factors. The current document provides an overview of the ‘life course’ of research projects requiring harmonization of existing data and highlights key elements to be considered from the inception to the end of the project.
Data suggest poorer bereavement outcomes for lesbian, gay and bisexual people, but this has not been estimated in population-based research. This study compared bereavement outcomes for partners of same-gender and different-gender decedents.
Methods
In this population-based, cross-sectional survey of people bereaved of a civil partner or spouse 6–10 months previously, we used adjusted logistic and linear regression to investigate outcomes of interest: (1) positive screen on Inventory of Complicated Grief (ICG), (2) positive screen on General Health Questionnaire (GHQ), (3) grief intensity (ICG) and (4) psychiatric symptoms (GHQ-12).
Results
Among 233 same-gender partners and 329 of different-gender partners, 66.1% [95% confidence interval (CI) 60.0–72.2] and 59.2% [95% CI (53.9–64.6)] respectively screened positive for complicated grief on the ICG, whilst 76.0% [95% CI (70.5–81.5)] and 69.3% [95% CI (64.3–74.3)] respectively screened positive on the GHQ-12. Same-gender bereaved partners were not significantly more likely to screen positive for complicated grief than different-gender partners [adjusted odds ratio (aOR) 1.56, 95% CI (0.98–2.47)], p = 0.059, but same-gender bereaved partners were significantly more likely to screen for psychiatric caseness [aOR 1.67 (1.02, 2.71) p = 0.043]. We similarly found no significant association of partner gender with grief intensity [B = 1.86, 95% CI (−0.91to 4.63), p = 0.188], but significantly greater psychological distress for same-gender partners [B = 1.54, 95% CI (−0.69–2.40), p < 0.001].
Conclusions
Same-gender bereaved partners report significantly more psychological distress. In view of their poorer sub-clinical mental health, clinical and bereavement services should refine screening processes to identify those at risk of poor mental health outcomes.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Dying is mostly seen as a dreadful event, never a happy experience. Yet, as palliative care physicians, we have seen so many patients who remained happy despite facing death. Hence, we conducted this qualitative study to explore happiness in palliative care patients at the University of Malaya Medical Centre.
Method
Twenty terminally ill patients were interviewed with semi-structured questions. The results were thematically analyzed.
Results
Eight themes were generated: the meaning of happiness, connections, mindset, pleasure, health, faith, wealth, and work. Our results showed that happiness is possible at the end of life. Happiness can coexist with pain and suffering. Social connections were the most important element of happiness at the end of life. Wealth and work were given the least emphasis. From the descriptions of our patients, we recognized a tendency for the degree of importance to shift from the hedonic happiness to eudaimonic happiness as patients experienced a terminal illness.
Significance of results
To increase the happiness of palliative care patients, it is crucial to assess the meaning of happiness for each patient and the degree of importance for each happiness domain to allow targeted interventions.
To improve speech emotion recognition, a U-acoustic words emotion dictionary (AWED) features model is proposed based on an AWED. The method models emotional information from acoustic words level in different emotion classes. The top-list words in each emotion are selected to generate the AWED vector. Then, the U-AWED model is constructed by combining utterance-level acoustic features with the AWED features. Support vector machine and convolutional neural network are employed as the classifiers in our experiment. The results show that our proposed method in four tasks of emotion classification all provides significant improvement in unweighted average recall.
The only generally accepted treatment of coeliac disease (CD) is a lifelong gluten-free diet. Wheat gluten proteins include gliadins, low and high molecular weight glutenins. However, we have found significant structural variations within these protein families among different cultivars. To determine which structural motifs might be less toxic than others, we assessed five variants of α-gliadin immunodominant CD-toxic peptides synthesised as 16mers in CD T cell stimulation assays with gluten-sensitive T cell lines generated from duodenal biopsies from CD-affected individuals. The peptides harboured the overlapping T cell epitopes DQ 2.5-glia-α-2 and naturally occurring variants that differed in certain amino acids (AA). The results revealed that introduction of two selected AA substitutions in α-gliadin peptides reduced immunogenicity. A peptide with three AA substitutions involving two glutamic acids (E) and one glutamine residue (G) revealed the peptide was negative in 5:5 samples. We used CD small-intestinal organ culture to assess CD toxicity that revealed two peptides with selected substitution of both glutamic acid (E) and proline (P) residues abrogated evidence of CD toxicity.
Hundreds of penetrant risk loci have been identified across different neurodevelopmental disorders (NDDs), and these often involve rare (<1% frequency) copy number variations (CNVs), which can involve one or more genes. Monozygotic (MZ) twin pairs are long thought to share 100% of their genomic information. However, genetic differences in the form of postzygotic somatic variants have been reported recently both in typically developing (TD) and in clinically discordant MZ pairs. We sought to investigate the contribution of rare CNVs in 100 twin pairs enriched for NDD phenotypes with a particular focus on postzygotic CNVs in MZ pairs discordant for autism spectrum disorder (ASD) using the Illumina Infinium PsychArray. In our sample, no postzygotic de novo CNVs were found in 55 MZ twin pairs, including the 13 pairs discordant for ASD. We did detect a higher rate of CNVs overlapping genes involved in disorders of the nervous system, such as a rare deletion affecting HNRNPU, in MZ pairs discordant and concordant for ASD in comparison with TD pairs (p = .02). Our results are in concordance with earlier findings that postzygotic de novo CNV events are typically rare in genomic DNA derived from saliva or blood, and suggests that the discordance of NDDs in our sample of twins is not explained by discordant CNVs. Still, studies investigating postzygotic variation in MZ discordant twins using DNA from different tissues and single cells and higher resolution genomics are needed in the future.
Since the 19th century, the continual discussion in the international community regarding how to protect industrial rights and intellectual property gradually resulted in a good number of international treaties that formed the basis of the intellectual property law in each country. However, in the current era of the knowledge economy, people realize more than ever that a successful model of knowledge management requires more than legal protection. It requires good control over the value chain, from the initiation of a new idea to the final commercialization (Polanyi, 1962).
When speaking of the theories and practices of intellectual property management, it is impossible to ignore the developments in the United States over the past few decades. Starting in the early 1980s, the United States enacted a number of intellectual-property-related acts that allowed relevant authorities to put into practical use the stock of intellectual property assets “frozen” in government agencies and universities. The most prominent of these acts is the Bayh-Dole Act, which has served as the foundation for establishing cooperative relationships among universities, industries, and research institutes since its entry into force (Liu & Hung, 2004). The U.S. model later became a huge success in the 1990s. After that time, more and more countries tried to follow this model. For example, Japan's effort in introducing the Universities Technology Licensing Office Act was widely believed to be a copy of the Bayh-Dole model.
This chapter discusses the efforts being made in East Asia towards financial integration, and the prospects for it becoming generally accepted as a consensus goal of national policies. At present, financial integration in East Asia is largely a discussion topic for national officials in regional gatherings, both formal and bilateral and the subject of research, rather than a planned objective or even a limited agreed direction of policy. At the same time, several separate motives and common external forces have caused an increase in discussion of prospects for financial cooperation and integration in East Asia, and greater cooperation among national interests that traditionally compete in economic, financial and trade objectives. This has made the possibility of an agreement on financial integration as a deliberate objective more tangible than before.
This chapter begins with a discussion of the reasons underlying discussions relating to East Asian financial cooperation and integration (section II). It then reviews progress to date in a number of areas, of which the most significant are initiatives involving regional economic cooperation and Asian bond market development (section III). In looking to possible future developments, it is useful to compare the experience to date of the most successful regional financial integration initiative, that of the European Union (EU) (section IV).
Inappropriate heart rate response to exercise – chronotropic incompetence – and exercise intolerance are common in patients with a systemic right ventricle. We aimed to assess the relationship between heart rate increase, oxygen consumption, and timing of the right ventricular cardiac cycle in this cohort.
Methods
We prospectively studied nine patients with systemic right ventricles and pre-existing pacemakers using Doppler-echocardiography and treadmill exercise testing. Echocardiography was performed at increasing heart rates. Exercise tests were performed with baseline pacemaker settings and with optimised heart rate response in random order. In addition, eight age- and gender-matched controls underwent exercise testing using a similar exercise protocol.
Results
Patients with a systemic right ventricle had significantly lower peak oxygen consumption compared to controls – 12.6 plus or minus 6.8 versus 31.4 plus or minus 6.6 metres per kilogram per minute (p = 0.0006) – at baseline and active pacemaker reprogramming failed to increase peak oxygen consumption in this cohort – 12.6 plus or minus 6.8 versus 12.4 plus or minus 4.9 millilitres per kilogram per minute (p = NS) at baseline and with reprogramming, respectively. We found not only a marked increase in total isovolumic time but also a significant reduction in total filling time and the aortic velocity time integral, p-value is less than 0.001 for all, at higher heart rates compared to baseline conditions.
Conclusion
This study suggests that despite chronotropic incompetence at baseline, rate-responsive pacing does not improve exercise capacity in patients with a systemic right ventricle. It further indicates that high heart rates may be detrimental in these patients by reducing diastolic filling and stroke volume. These findings may have clinical implications when considering implantation of a permanent pacemaker in this cohort.