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Studies on humans that exploit contemporary data-intensive, high-throughput ‘omic’ assay technologies, such as genomics, transcriptomics, proteomics and metabolomics, have unequivocally revealed that humans differ greatly at the molecular level. These differences, which are compounded by each individual’s distinct behavioral and environmental exposures, impact individual responses to health interventions such as diet and drugs. Questions about the best way to tailor health interventions to individuals based on their nuanced genomic, physiologic, behavioral, etc. profiles have motivated the current emphasis on ‘precision’ medicine. This review’s purpose is to describe how the design and execution of N-of-1 (or personalized) multivariate clinical trials can advance the field. Such trials focus on individual responses to health interventions from a whole-person perspective, leverage emerging health monitoring technologies, and can be used to address the most relevant questions in the precision medicine era. This includes how to validate biomarkers that may indicate appropriate activity of an intervention as well as how to identify likely beneficial interventions for an individual. We also argue that multivariate N-of-1 and aggregated N-of-1 trials are ideal vehicles for advancing biomedical and translational science in the precision medicine era since the insights gained from them can not only shed light on how to treat or prevent diseases generally, but also provide insight into how to provide real-time care to the very individuals who are seeking attention for their health concerns in the first place.
This study aimed to analyse the temporal and spatial trends in the burden of anxiety disorders and major depressive disorder related to bullying victimisation on global, regional and country scales.
Data were from the 2019 Global Burden of Disease (GBD) Study. We assessed the global disability-adjusted life years (DALYs, per 100 000 population) of anxiety disorders and major depressive disorder attributable to bullying victimisation by age, sex and geographical location. The percentage changes in age-standardised rates of DALYs were used to quantify temporal trends, and the annual rate changes across 204 countries and territories were used to present spatial trends. Furthermore, we examined the relationship between the sociodemographic index (SDI) and the burden of anxiety disorders as well as major depressive disorder attributable to bullying victimisation and its spatial and temporal characteristics globally.
From 1990 to 2019, the global DALY rates of anxiety disorders and major depressive disorder attributable to bullying victimisation increased by 23.31 and 26.60%, respectively, with 27.27 and 29.07% for females and 18.88 and 23.84% for males. Across the 21 GBD regions, the highest age-standardised rates of bullying victimisation-related DALYs for anxiety disorders were in North Africa and the Middle East and for major depressive disorder in High-income North America. From 1990 to 2019, the region with the largest percentage increase in the rates of DALYs was High-income North America (54.66% for anxiety disorders and 105.88% for major depressive disorder), whereas the region with the slowest growth rate or largest percentage decline was East Asia (1.71% for anxiety disorders and −25.37% for major depressive disorder). In terms of SDI, this study found overall upward trends of bullying-related mental disorders in areas regardless of the SDI levels, although there were temporary downward trends in some stages of certain areas.
The number and rates of DALYs of anxiety disorders and major depressive disorder attributable to bullying victimisation increased from 1990 to 2019. Effective strategies to eliminate bullying victimisation in children and adolescents are needed to reduce the burden of anxiety disorders and major depressive disorder. Considering the large variations in the burden by SDI and geographic location, future protective actions should be developed based on the specific cultural contexts, development status and regional characteristics of each country.
Methicillin-resistant Staphylococcus aureus (MRSA) is a significant nosocomial pathogen in the ICU. MRSA contamination of healthcare personnel (HCP) gloves and gowns after providing care to patients with MRSA occurs at a rate of 14%–16% in the ICU setting. Little is known about whether the MRSA isolates identified on HCP gown and gloves following patient care activities are the same as MRSA isolates identified as colonizing or infecting the patient.
From a multisite cohort of 388 independent patient MRSA isolates and their corresponding HCP gown and glove isolates, we selected 91 isolates pairs using a probability to proportion size (PPS) sampling method. To determine whether the patient and HCP gown or gloves isolates were genetically similar, we used 5 comparative genomic typing methods: phylogenetic analysis, spa typing, multilocus sequence typing (MLST), large-scale BLAST score ratio (LSBSR), and single-nucleotide variant (SNV) analysis.
We identified that 56 (61.5%) of isolate pairs were genetically similar at least by 4 of the methods. Comparably, the spa typing and the LSBSR analyses revealed that >75% of the examined isolate pairs were concordant, with the thresholds established for each analysis.
Many of the patient MRSA isolates were genetically similar to those on the HCP gown or gloves following a patient care activity. This finding indicates that the patient is often the primary source of the MRSA isolates transmitted to the HCP, which can potentially be spread to other patients or hospital settings through HCP vectors. These results have important implications because they provide additional evidence for hospitals considering ending the use of contact precautions (gloves and gowns) for MRSA patients.
Baseline data on local status of threatened species are often limited, and alternative information sources such as local ecological knowledge (LEK) have potential to provide conservation insights but require critical evaluation. We assess the usefulness of LEK to generate conservation evidence for the Hainan Peacock-pheasant Polyplectron katsumatae, a poorly known threatened island galliform. Interview surveys in rural communities across eight forested landscapes on Hainan provided a new dataset of sightings of Peacock-pheasants and other galliforms. Fewer respondents had seen Peacock-pheasants compared to other species across most landscapes, although Peacock-pheasant sightings showed significant across-landscape variation, with substantially more total and recent sightings from Yinggeling National Nature Reserve. However, validation of interview data with camera trapping data from Houmiling Provincial Nature Reserve, a landscape with few reported sightings, suggests a more optimistic possible status for Peacock-pheasants, which were detected as frequently as Red Junglefowl Gallus gallus and Silver Pheasant Lophura nycthemera during systematic camera trap placement. Hainan Peacock-pheasant sighting rates might be influenced by various factors (e.g. restricted local access to forests), with absolute abundance possibly greater than expected from limited sightings. Conversely, relative across-landscape abundance patterns from LEK are likely to be valid, as similar detection biases exist across surveyed landscapes.
In fostering community and culture through entertainment in shared spaces, performing arts venues have also become targets of terrorism. A greater understanding of these attacks is needed to assess the risk posed to different types of venues, to inform medical disaster preparedness, to anticipate injury patterns, and to reduce preventable deaths.
A search of the Global Terrorism Database (GTD) was conducted from the year 1970 through 2019. Using pre-coded variables for target/victim type and target subtype, attacks involving “business” and “entertainment/cultural/stadium/casino” were identified. Attacks targeting performing arts venues were selected using the search terms “theater,” “theatre,” “auditorium,” “center,” “hall,” “house,” “concert,” “music,” “opera,” “cinema,” and “movie.” Manual review by two authors was performed to confirm appropriateness for inclusion of entries involving venues where the primary focus of the audience was to view a performance. Descriptive statistics were performed using R (version 3.6.1).
A total of 312 terrorist attacks targeting performing arts venues were identified from January 1, 1970 through December 31, 2019. Two-hundred nine (67.0%) attacks involved cinemas or movie theaters, 80 (25.6%) involved unspecified theaters, and 23 (7.4%) specifically targeted live music performance venues. Two-hundred thirty-four (75.0%) attacks involved a bombing or explosion, 50 (16.0%) damaged a facility or infrastructure, and 17 (5.4%) included armed assault. Perpetrators used explosives in 234 (75.0%) attacks, incendiary weapons in 50 (16.0%) attacks, and firearms in 19 (6.1%) attacks. In total, attacks claimed the lives of 1,307 and wounded 4,201 persons. Though fewer in number, attacks against music venues were responsible for 29.4% of fatalities and 35.0% of those wounded, and more frequently involved the use of firearms. Among 95 attacks falling within the highest quartile for victims killed or wounded (>two killed and/or >ten wounded), 83 (87.4%) involved explosives, seven (7.4%) involved firearms, and three (3.2%) involved incendiary methods.
While uncommon, terrorist attacks against performing arts venues carry the risk for mass casualties, particularly when explosives and firearms are used.
We report the experimental results of the commissioning phase in the 10 PW laser beamline of the Shanghai Superintense Ultrafast Laser Facility (SULF). The peak power reaches 2.4 PW on target without the last amplifying during the experiment. The laser energy of 72 ± 9 J is directed to a focal spot of approximately 6 μm diameter (full width at half maximum) in 30 fs pulse duration, yielding a focused peak intensity around 2.0 × 1021 W/cm2. The first laser-proton acceleration experiment is performed using plain copper and plastic targets. High-energy proton beams with maximum cut-off energy up to 62.5 MeV are achieved using copper foils at the optimum target thickness of 4 μm via target normal sheath acceleration. For plastic targets of tens of nanometers thick, the proton cut-off energy is approximately 20 MeV, showing ring-like or filamented density distributions. These experimental results reflect the capabilities of the SULF-10 PW beamline, for example, both ultrahigh intensity and relatively good beam contrast. Further optimization for these key parameters is underway, where peak laser intensities of 1022–1023 W/cm2 are anticipated to support various experiments on extreme field physics.
To determine the impact of various aerosol mitigation interventions and to establish duration of aerosol persistence in a variety of dental clinic configurations.
We performed aerosol measurement studies in endodontic, orthodontic, periodontic, pediatric, and general dentistry clinics. We used an optical aerosol spectrometer and wearable particulate matter sensors to measure real-time aerosol concentration from the vantage point of the dentist during routine care in a variety of clinic configurations (eg, open bay, single room, partitioned operatories). We compared the impact of aerosol mitigation strategies (eg, ventilation and high-volume evacuation (HVE), and prevalence of particulate matter) in the dental clinic environment before, during, and after high-speed drilling, slow–speed drilling, and ultrasonic scaling procedures.
Conical and ISOVAC HVE were superior to standard-tip evacuation for aerosol-generating procedures. When aerosols were detected in the environment, they were rapidly dispersed within minutes of completing the aerosol-generating procedure. Few aerosols were detected in dental clinics, regardless of configuration, when conical and ISOVAC HVE were used.
Dentists should consider using conical or ISOVAC HVE rather than standard-tip evacuators to reduce aerosols generated during routine clinical practice. Furthermore, when such effective aerosol mitigation strategies are employed, dentists need not leave dental chairs fallow between patients because aerosols are rapidly dispersed.
A proportion of patients with bipolar disorder (BD) manifests with only unipolar mania (UM). This study examined relevant clinical features and psychosocial characteristics in UM compared with depressive-manic (D-M) subgroups. Moreover, comorbidity patterns of physical conditions and psychiatric disorders were evaluated between the UM and D-M groups.
This clinical retrospective study (N = 1015) analyzed cases with an average of 10 years of illness duration and a nationwide population-based cohort (N = 8343) followed up for 10 years in the Taiwanese population. UM was defined as patients who did not experience depressive episodes and were not prescribed adequate antidepressant treatment during the disease course of BD. Logistic regression models adjusted for relevant covariates were used to evaluate the characteristics and lifetime comorbidities in the two groups.
The proportion of UM ranged from 12.91% to 14.87% in the two datasets. Compared with the D-M group, the UM group had more psychotic symptoms, fewer suicidal behaviors, a higher proportion of morningness chronotype, better sleep quality, higher extraversion, lower neuroticism, and less harm avoidance personality traits. Substantially different lifetime comorbidity patterns were observed between the two groups.
Patients with UM exhibited distinct clinical and psychosocial features compared with patients with the D-M subtype. In particular, a higher risk of comorbid cardiovascular diseases and anxiety disorders is apparent in patients with D-M. Further studies are warranted to investigate the underlying mechanisms for diverse presentations in subgroups of BDs.
The Canadian Nosocomial Infection Surveillance Program conducted point-prevalence surveys in acute-care hospitals in 2002, 2009, and 2017 to identify trends in antimicrobial use.
Eligible inpatients were identified from a 24-hour period in February of each survey year. Patients were eligible (1) if they were admitted for ≥48 hours or (2) if they had been admitted to the hospital within a month. Chart reviews were conducted. We calculated the prevalence of antimicrobial use as follows: patients receiving ≥1 antimicrobial during survey period per number of patients surveyed × 100%.
In each survey, 28−47 hospitals participated. In 2002, 2,460 (36.5%; 95% CI, 35.3%−37.6%) of 6,747 surveyed patients received ≥1 antimicrobial. In 2009, 3,566 (40.1%, 95% CI, 39.0%−41.1%) of 8,902 patients received ≥1 antimicrobial. In 2017, 3,936 (39.6%, 95% CI, 38.7%−40.6%) of 9,929 patients received ≥1 antimicrobial. Among patients who received ≥1 antimicrobial, penicillin use increased 36.8% between 2002 and 2017, and third-generation cephalosporin use increased from 13.9% to 18.1% (P < .0001). Between 2002 and 2017, fluoroquinolone use decreased from 25.7% to 16.3% (P < .0001) and clindamycin use decreased from 25.7% to 16.3% (P < .0001) among patients who received ≥1 antimicrobial. Aminoglycoside use decreased from 8.8% to 2.4% (P < .0001) and metronidazole use decreased from 18.1% to 9.4% (P < .0001). Carbapenem use increased from 3.9% in 2002 to 6.1% in 2009 (P < .0001) and increased by 4.8% between 2009 and 2017 (P = .60).
The prevalence of antimicrobial use increased between 2002 and 2009 and then stabilized between 2009 and 2017. These data provide important information for antimicrobial stewardship programs.
We report on experimental observation of non-laminar proton acceleration modulated by a strong magnetic field in laser irradiating micrometer aluminum targets. The results illustrate the coexistence of ring-like and filamentation structures. We implement the knife edge method into the radiochromic film detector to map the accelerated beams, measuring a source size of 30–110 μm for protons of more than 5 MeV. The diagnosis reveals that the ring-like profile originates from low-energy protons far off the axis whereas the filamentation is from the near-axis high-energy protons, exhibiting non-laminar features. Particle-in-cell simulations reproduced the experimental results, showing that the short-term magnetic turbulence via Weibel instability and the long-term quasi-static annular magnetic field by the streaming electric current account for the measured beam profile. Our work provides direct mapping of laser-driven proton sources in the space-energy domain and reveals the non-laminar beam evolution at featured time scales.
Success of any needle-based medical procedures depends on accurate placement of the needle at the target location. However, accurate targeting and control of flexible self-actuating (active) needle are challenging. We have developed a shape memory alloy-actuated flexible needle steered by a 3D Cartesian robot and performed a comparative study of four, non-model-based, coordinated control methodologies for the combined robot steering and flexible-needle insertion process for surgical interventions. Investigated four controllers are: proportional–integral–derivative (PID), PID with the cubic of positional error term (PID-P3), static PID sliding mode controller, and robust adaptive PID sliding mode controller (RAPID-SMC). Relative efficacies of these controllers are demonstrated by performing experiements using a tissue-mimicking soft material phantom. Results from experiments have reavealed that RAPID-SMC is superior to other three controllers.
In recent years ‘social enterprises’ have become important partners in the delivery of key public services such as healthcare. However, little is known about how healthcare social enterprises contribute to public service provision in the health sector. We analyzed 172 social enterprises from four continents involved in healthcare to assess the types of interventions, processes, and roles they play responding to rapidly evolving healthcare systems. We found that they are engaged broadly in three dimensions of health service provision: improving access to health services; improving the quality of health services; and building public health capacity. We contribute to social policy theory by enhancing understanding of the micro-level interventions of social enterprises in the healthcare sector and articulating new dimensions of NPG that include co-innovation, co-lobbying, and co-integration in the context of healthcare.
Diverse and abundant fossil taxa have been described in the lower Cambrian Shipai Formation in the Three Gorges area of Hubei Province, South China, but the taxonomy and diversity of the co-occurring brachiopod fauna are still far from clear. Here we describe the brachiopod fauna recovered from the Shipai Formation in the Three Gorges area of South China, including representatives of the subphylum Linguliformea: linguloids (Lingulellotreta ergalievi, Eoobolus malongensis, and Neobolidae gen. indet. sp. indet.), and an acrotretoid (Linnarssonia sapushanensis); and representatives from the subphylum Rhynchonelliformea: the calcareous-shelled Kutorginates (Kutorgina sinensis, Kutorgina sp., and Nisusia liantuoensis). This brachiopod assemblage and the first occurrence of Linnarssonia sapushanensis shell beds permit correlation of the Shipai Formation in the Three Gorges area of Hubei Province with the Stage 4 Wulongqing Formation in the Wuding area of eastern Yunnan. This correlation is further strengthened by the first appearance datum (FAD) of the rhynchonelliform brachiopod Nisusia in the upper silty mudstone of both the Shipai and Wulongqing formations. The new well-preserved material, derived from siliciclastic rocks, also gives critical new insights into the fine shell structure of L. sapushanensis. Microstructural studies on micromorphic acrotretoids (like Linnarssonia) have previously been restricted to fossils that were acid-etched from limestones. This is the first study to carry out detailed comparative ultrastructural studies on acrotretoid shells preserved in siliciclastic rocks. This work reveals a hollow tube and solid column microstructure in the acrotretoid shells from the Shipai Formation, which is likely to be equivalent of traditional column and central canal observed in shells dissolved from limestones.
Among older people with cognitive impairment and mild dementia, relatively little is known about the factors that predict preferences for everyday living activities and experiences and that influence the relative importance of those activities and experiences.
Participants were recruited from the Massachusetts Alzheimer’s Disease Research Center (MADRC) Clinical Core longitudinal cohort.
The sample included 62 community-dwelling older adults with cognitive impairment (Clinical Dementia Rating global score ≥ 0.5).
We used the Preferences for Everyday Living Inventory (PELI) to assess preferences for activities and lifestyle experiences among persons with cognitive impairment. Within-subjects analysis of variance was used to test for significant differences in the mean ratings of importance for four domains of the PELI (“autonomous choice,” “social engagement,” “personal growth,” and “keeping a routine”). Multiple regression models were used to relate predictors, including neuropsychiatric symptoms, to importance ratings for each domain.
Significant differences were noted in the mean importance ratings of the preferences domains: “social engagement” preferences were rated as most important, followed by “autonomous choice,” “personal growth,” and “keeping a routine.” For the “social engagement” preferences domain, female sex was significantly associated with higher importance of “social engagement,” while depressive symptoms (Geriatric Depression Scale-15 scores) were significantly associated with lower importance.
This study adds novel insight into the everyday preferences of community-dwelling older adults with cognitive impairment and highlights the impact of a number of factors, particularly level of depression, on how important various everyday experiences are perceived.
In order to maximize the utility of future studies of trilobite ontogeny, we propose a set of standard practices that relate to the collection, nomenclature, description, depiction, and interpretation of ontogenetic series inferred from articulated specimens belonging to individual species. In some cases, these suggestions may also apply to ontogenetic studies of other fossilized taxa.
To investigate the association between parity and the risk of incident dementia in women.
We pooled baseline and follow-up data for community-dwelling women aged 60 or older from six population-based, prospective cohort studies from four European and two Asian countries. We investigated the association between parity and incident dementia using Cox proportional hazards regression models adjusted for age, educational level, hypertension, diabetes mellitus and cohort, with additional analysis by dementia subtype (Alzheimer dementia (AD) and non-Alzheimer dementia (NAD)).
Of 9756 women dementia-free at baseline, 7010 completed one or more follow-up assessments. The mean follow-up duration was 5.4 ± 3.1 years and dementia developed in 550 participants. The number of parities was associated with the risk of incident dementia (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02–1.13). Grand multiparity (five or more parities) increased the risk of dementia by 30% compared to 1–4 parities (HR = 1.30, 95% CI = 1.02–1.67). The risk of NAD increased by 12% for every parity (HR = 1.12, 95% CI = 1.02–1.23) and by 60% for grand multiparity (HR = 1.60, 95% CI = 1.00–2.55), but the risk of AD was not significantly associated with parity.
Grand multiparity is a significant risk factor for dementia in women. This may have particularly important implications for women in low and middle-income countries where the fertility rate and prevalence of grand multiparity are high.
We apply conformal mapping to find the evolving shapes of a dissolving cylinder in a potential flow. Similar equations can be used to describe melting in a flowing liquid phase. Results are compared with microfluidic experiments and numerical simulations. Shapes predicted by conformal mapping agree almost perfectly with experimental observations, after a modest (20 %) rescaling of the time. Finite-volume simulations show that the differences with experiment are connected to the underlying assumptions of the analytical model: potential flow and diffusion-limited dissolution. Approximate solutions of the equations describing the evolution of the shape of the undissolved solid can be derived from a Laurent expansion of the mapping function from the unit circle. Asymptotic expressions for the evolution of the area of the disk and the shift in its centre of mass have been derived at low and high Péclet number. Analytic approximations to the leading-order Laurent coefficients provide additional insight into the mechanisms underlying pore-scale dissolution.
Background: Healthcare personnel (HCP) acquire MRSA on their gown and gloves during routine care activities for patients who are colonized or infected with MRSA at a rate of ∼15%. Certain care activities (eg, physical exam, care of endotracheal tube, wound care and bathing/hygiene) have been associated with a higher frequency of transmission from the patient to HCP gown and gloves than other activities (ie, administration of oral medicines, glucose monitoring, and manipulation of IV tubing/medication delivery). However, quantification of MRSA contamination and risk to subsequent patients is poorly defined. Objective: We sought to determine the mean MRSA colony-forming units (CFU) found on the gloves and gowns of HCP who acquire MRSA after various care activities involving patients with MRSA. Methods: We conducted a prospective cohort study at the University of Maryland Medical Center from December 2018 to October 2019. We identified patients colonized or infected with MRSA based on culture data from the prior 7 days. HCP performing prespecified care activities on eligible patients were observed. To isolate the risk of each care activity, HCP donned new gloves and gown prior to a specific care activity. Once that care activity was performed, HCP gloves and gown were swabbed prior to the any further care activities. HCP gloves were cultured with an E-swab by swabbing each digit up and down 3 times followed by 2 circles on the palm of their hands. HCP gowns were sampled by swabbing a 15 × 30-cm area along the beltline of the gown and along each inner forearm twice. E-swab liquid was then serially diluted and plated in triplicate on CHROMagar MRSA II (BD, Sparks, MD) to obtain CFU. We calculated the median CFUs and the interquartile range (IQR) for each specific care activity stratified by gown and gloves. Results: In total, 604 HCP–patient care interactions were observed. Table 1 displays the mean MRSA CFUs stratified by gown and gloves for each patient care activity of interest. Conclusions: The quantity of MRSA found on gowns and gloves varies depending on patient care activities. Recognition of differential transmission rates between various activities may allow different approaches to infection prevention, such as the use of personal protective equipment in high- versus low-risk activities and/or the use of more aggressive interventions for high-risk activities.
A 2-year fertilization experiment was conducted to study the effect of different ratios of organic (pig) manure on wheat yield and nitrogen use efficiency (NUE). The four treatments were no nitrogen (N) (CK); 100% chemical fertilizer N (urea; T1); 70% chemical fertilizer N + 30% organic manure N (T2) and 50% chemical fertilizer N + 50% organic manure N (T3), with the same amount of applied nitrogen (120 kg/ha). The results showed the maximum grain yield (3049 kg/ha), crop nitrogen uptake (216 kg/ha), NUE (65.4%) and accumulated nitrate nitrogen (NO3−-N in 0–200 cm, 142 kg/ha) were observed in the T1 among all treatments in the first year. However, the largest grain yield (5074 kg/ha), crop nitrogen uptake (244 kg/ha) and NUE (82.5%) were under T2 treatment in the second year. Furthermore, T2 had the maximum NO3−-N content in 0–100 cm layer (116 kg/ha), especially 0–40 cm layer, and the lowest NO3−-N content in 100–200 cm (58.8 kg/ha). However, 50% organic manure N in T3 increased apparent nitrogen loss by 39.0% compared to that in T2. Therefore, 30% organic manure N application was more conducive for enhancing wheat yield and NUE and promoting environmental safety after 1-year fertilization time.