The Anglo-Saxon migration and the formation of the early English gene pool.

The history of the British Isles and Ireland is characterized by multiple periods of major cultural change, including the influential transformation after the end of Roman rule, which precipitated shifts in language, settlement patterns and material culture1. The extent to which migration from continental Europe mediated these transitions is a matter of long-standing debate2-4. Here we study genome-wide ancient DNA from 460 medieval northwestern Europeans-including 278 individuals from England-alongside archaeological data, to infer contemporary population dynamics. We identify a substantial increase of continental northern European ancestry in early medieval England, which is closely related to the early medieval and present-day inhabitants of Germany and Denmark, implying large-scale substantial migration across the North Sea into Britain during the Early Middle Ages. As a result, the individuals who we analysed from eastern England derived up to 76% of their ancestry from the continental North Sea zone, albeit with substantial regional variation and heterogeneity within sites. We show that women with immigrant ancestry were more often furnished with grave goods than women with local ancestry, whereas men with weapons were as likely not to be of immigrant ancestry. A comparison with present-day Britain indicates that subsequent demographic events reduced the fraction of continental northern European ancestry while introducing further ancestry components into the English gene pool, including substantial southwestern European ancestry most closely related to that seen in Iron Age France5,6.

National influenza mid-season report, 2022-2023: A rapid and early epidemic onset.

Canada's 2022-2023 national influenza epidemic was declared in epidemiological week 43 (week ending October 29, 2022), relatively early in comparison to historical seasons. This year marks the return to pre-pandemic-like influenza circulation, following the brief and delayed influenza epidemic declared in the spring of the 2021-2022 season. To date this season, 59,459 detections of influenza have been reported out of 456,536 tests; both values exceeding historical averages. This epidemic is being fundamentally driven by influenza A, with influenza A(H3N2) accounting for 94% of subtyped detections. This season to date has had a significant impact on adolescents and young children, with a high proportion of detections occurring in those aged 0-19 years (42%). Provinces and territories have reported higher than usual influenza-associated hospitalizations, intensive care unit admissions, and deaths in comparison with previous seasons; in particular, paediatric hospitalization incidence was persistently far above historical peak levels for several weeks. The return of seasonal influenza circulation highlights the importance of sustained vigilance with regard to influenza and employment of available mitigation measures, especially of annual seasonal influenza vaccination.

National Influenza Annual Report, Canada, 2022-2023: Canada's first fall epidemic since the 2019-2020 season.

Coinciding with the beginning of the coronavirus disease 2019 (COVID-19) pandemic in March 2020, Canadian seasonal influenza circulation was suppressed, which was a trend reported globally. Canada saw a brief and delayed return of community influenza circulation during the spring of the 2021-2022 influenza season. Surveillance for Canada's 2022-2023 seasonal influenza epidemic began in epidemiological week 35 (week starting August 28, 2022) and ended in epidemiological week 34 (week ending August 26, 2023). The 2022-2023 season marked the return to pre-pandemic-like influenza circulation. The epidemic began in epidemiological week 43 (week ending October 29, 2022) and lasted 10 weeks. Driven by influenza A(H3N2), the epidemic was relatively early, extraordinary in intensity, and short in length. This season, a total of 74,344 laboratory-confirmed influenza detections were reported out of 1,188,962 total laboratory tests. A total of 93% of detections were influenza A (n=68,923). Influenza A(H3N2) accounted for 89% of the subtyped specimens (n=17,638/19,876). Late-season, Canada saw community circulation of influenza B for the first time since the 2019-2020 season. The 2022-2023 influenza season in Canada had an extraordinary impact on children and youth; nearly half (n=6,194/13,729, 45%) of reported influenza A(H3N2) detections were in the paediatric (younger than 19 years) population. Weekly paediatric influenza-associated hospital admissions were persistently above historical peak levels for several weeks. The total number of influenza-associated paediatric hospitalizations (n=1,792) far exceeded historical averages (n=1,091). With the return of seasonal influenza circulation and endemic co-circulation of multiple high burden respiratory viruses, sustained vigilance is warranted. Annual seasonal influenza vaccination is a key public health intervention available to protect Canadians.

National FluWatch mid-season report, 2021-2022: Sporadic influenza activity returns.

Surveillance for Canada's 2021-2022 seasonal influenza epidemic began in epidemiological week 35 (the week starting August 29, 2021) during the ongoing coronavirus disease 2019 (COVID-19) global public health emergency. In the 2021-2022 surveillance season to date, there has been a return of persistent sporadic influenza activity, and the first influenza-associated hospitalizations since mid-2020 have been reported. However, as of week 52 (week ending 01/01/2022) activity has remained sporadic, and no influenza-confirmed outbreaks or epidemic activity have been detected. There has been a delay or absence in several traditional seasonal influenza milestones, including the declared start of the influenza season, marked by a threshold of 5% positivity, which historically has occurred on average in week 47. The 429 sporadic detections reported in Canada to date have occurred in 31 regions across seven provinces/territories. Nearly half (n=155/335, 46.3%) of reported cases have been in the paediatric (younger than 19 years) population. Three-quarters of the cases were influenza A detections (n=323/429, 75.3%). Of the subtyped influenza A detections, A(H3N2) predominated (n=83/86, 96.5%). Of the 12 viruses characterized by the National Microbiology Laboratory, 11 were seasonal strains. Among the seasonal strains characterized, only one was antigenically similar to the strains recommended for the 2021-2022 Northern Hemisphere vaccine, though all were sensitive to the antivirals, oseltamivir and zanamivir. Until very recently, seasonal influenza epidemics had not been reported since March 2020. Evidence on the re-emergence of seasonal influenza strains in Canada following the A(H1N1)pdm09 pandemic shows that influenza A(H3N2) and B epidemics ceased through the 2009-2010 season and second wave of A(H1N1)pdm09, but then re-emerged in subsequent seasons to predominate causing epidemics of higher intensity than in the pre-pandemic seasons. When and where seasonal influenza epidemic activity resumes cannot be predicted, but model-based estimates and historical post-pandemic patterns of intensified epidemics warrant continued vigilance through the usual season and for out-of-season re-emergence. In addition, ongoing population preparedness measures, such as annual influenza vaccination to mitigate the intensity and burden of future seasonal influenza epidemic waves, should continue.

National Influenza Annual Report, Canada, 2021-2022: A brief, late influenza epidemic.

Canadian seasonal influenza circulation had been suppressed since the beginning of the coronavirus disease 2019 (COVID-19) pandemic. This suppression was reported globally and generated concern that the return of community influenza circulation could be intense and that co-circulation of influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was possible and potentially severe. Community circulation of influenza returned to Canada during the 2021-2022 influenza season. The influenza epidemic began in week 16 (mid-April 2022) and lasted only nine weeks. This epidemic was driven by influenza A(H3N2) and was exceptionally late in the season, low in intensity and short in length. Community co-circulation of influenza and SARS-CoV-2 was observed in Canada for the first time during the 2021-2022 seasonal influenza epidemic. The unusual characteristics of the 2021-2022 influenza epidemic suggest that a breadth of factors moderate transmission dynamics of the two viruses. Concerns of an intense seasonal influenza epidemic did not come to fruition during the 2021-2022 season; therefore, high influenza susceptibility remains, as does predisposition to larger influenza epidemics. Ongoing circulation of SARS-CoV-2 creates uncertainty about dynamics of future influenza epidemics, but influenza vaccination remains a key public health intervention available to protect Canadians. Public health authorities need to remain vigilant, maintain surveillance and continue to plan for both heightened seasonal influenza circulation and for the potential for endemic co-circulation of influenza and SARS-CoV-2.

National Influenza Annual Report, Canada, 2020-2021, in the global context.

During the 2020-2021 Canadian influenza season, no community circulation of influenza occurred. Only 69 positive detections of influenza were reported, and influenza percent positivity did not exceed 0.1%. Influenza indicators were at historical lows compared with the previous six seasons, with no laboratory-confirmed influenza outbreaks or severe outcomes being reported by any of the provinces and territories. Globally, influenza circulation was at historically low levels in both the Northern and the Southern Hemispheres. The decreased influenza activity seen in Canada and globally is concurrent with the implementation of non-pharmaceutical public health measures to mitigate the spread of the coronavirus disease 2019 (COVID-19). Although it is difficult to predict when influenza will begin to re-circulate, given the increased COVID-19 vaccination and the relaxation of public health measures, an influenza resurgence can be expected and may be more severe or intense than recent seasons. Influenza vaccination, along with non-pharmaceutical public health measures, continues to remain the best method to prevent the spread and impact of influenza. Public health authorities need to remain vigilant, maintain surveillance and continue to plan for heightened seasonal influenza circulation.

An itemized approach to assessing behavioral and psychological symptoms in dementia.

In an effort to obtain more detailed clinical information regarding behavioral and psychology symptoms in dementia, we submitted an existing, comprehensive measure of behavioral and psychology symptoms in dementia (Neuropsychiatric Inventory) to an alternate itemized scoring system. One hundred twenty-four caregivers of patients with dementia (mean Mini-Mental State Examination=22.6) rated the frequency of individual symptoms across all domains of the measure. Internal reliability and factor structures for all domains were analyzed to assess the stability of this scoring approach. Internal consistency alphas for each domain ranged from .57 to .91. Alpha reliability for the total inventory was .96. Results indicate an itemized approach to assessing behavioral and psychological symptoms in dementia among patients with mild-to-moderate dementia can be reliable, has the power to capture multiple features of neuropsychiatric symptoms, and can produce a rich neurobehavioral profile adding valuable information to the diagnosis and treatment of these patients.

Syntactic comprehension deficits are associated with MRI white matter alterations in dementia.

Comprehension difficulties associated with periventricular and deep white matter alterations (WMA) in mild dementia were investigated using portions of the Boston Diagnostic Aphasia Examination (BDAE) Complex Ideation subtest and Syntax subtests. Mild dementia participants were grouped according to the extent of their WMA as observed on magnetic resonance imaging (mild WMA n = 45 vs. moderate to severe WMA n = 52). Correlation and regression analyses also were performed to examine the link between WMA and comprehension abilities, as well as the link between comprehension abilities and neuropsychological measures of executive functioning, language, episodic memory, and overall dementia severity. Results showed that the WMA groups differed on the BDAE-Syntax subtests, with the severe WMA group demonstrating more impairment. Correlation and regression analyses including the entire sample also demonstrated that the extent of WMA was significantly linked to Syntax test scores but not Complex Ideation scores. Regression analyses including neuropsychological measures showed that the BDAE-Complex Ideation score was marginally predicted by only overall dementia severity, whereas the BDAE-Syntax scores were significantly predicted by independent measures of working memory/executive functioning. In conclusion, greater subcortical WMA and executive deficits are associated with greater difficulties in syntactic comprehension in individuals with mild dementia.

Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study.

BACKGROUND: More than 50 million people worldwide sustain a traumatic brain injury (TBI) annually. Detection of intracranial injuries relies on head CT, which is overused and resource intensive. Blood-based brain biomarkers hold the potential to predict absence of intracranial injury and thus reduce unnecessary head CT scanning. We sought to validate a test combining ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), at predetermined cutoff values, to predict traumatic intracranial injuries on head CT scan acutely after TBI. METHODS: This prospective, multicentre observational trial included adults (≥18 years) presenting to participating emergency departments with suspected, non-penetrating TBI and a Glasgow Coma Scale score of 9-15. Patients were eligible if they had undergone head CT as part of standard emergency care and blood collection within 12 h of injury. UCH-L1 and GFAP were measured in serum and analysed using prespecified cutoff values of 327 pg/mL and 22 pg/mL, respectively. UCH-L1 and GFAP assay results were combined into a single test result that was compared with head CT results. The primary study outcomes were the sensitivity and the negative predictive value (NPV) of the test result for the detection of traumatic intracranial injury on head CT. FINDINGS: Between Dec 6, 2012, and March 20, 2014, 1977 patients were recruited, of whom 1959 had analysable data. 125 (6%) patients had CT-detected intracranial injuries and eight (<1%) had neurosurgically manageable injuries. 1288 (66%) patients had a positive UCH-L1 and GFAP test result and 671 (34%) had a negative test result. For detection of intracranial injury, the test had a sensitivity of 0·976 (95% CI 0·931-0·995) and an NPV of 0·996 (0·987-0·999). In three (<1%) of 1959 patients, the CT scan was positive when the test was negative. INTERPRETATION: These results show the high sensitivity and NPV of the UCH-L1 and GFAP test. This supports its potential clinical role for ruling out the need for a CT scan among patients with TBI presenting at emergency departments in whom a head CT is felt to be clinically indicated. Future studies to determine the value added by this biomarker test to head CT clinical decision rules could be warranted. FUNDING: Banyan Biomarkers and US Army Medical Research and Materiel Command.

Risk, Timing, and Predictors of Disease Flare After Discontinuation of Anti-Tumor Necrosis Factor Therapy in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis With Clinically Inactive Disease.

OBJECTIVE: To determine the frequency, time to flare, and predictors of disease flare upon withdrawal of anti-tumor necrosis factor (anti-TNF) therapy in children with polyarticular forms of juvenile idiopathic arthritis (JIA) who demonstrated ≥6 months of continuous clinically inactive disease. METHODS: In 16 centers 137 patients with clinically inactive JIA who were receiving anti-TNF therapy (42% of whom were also receiving methotrexate [MTX]) were prospectively followed up. If the disease remained clinically inactive for the initial 6 months of the study, anti-TNF was stopped and patients were assessed for flare at 1, 2, 3, 4, 6, and 8 months. Life-table analysis, t-tests, chi-square test, and Cox regression analysis were used to identify independent variables that could significantly predict flare by 8 months or time to flare. RESULTS: Of 137 patients, 106 (77%) maintained clinically inactive disease while receiving anti-TNF therapy for the initial 6 months and were included in the phase of the study in which anti-TNF therapy was stopped. Stopping anti-TNF resulted in disease flare in 39 (37%) of 106 patients by 8 months. The mean/median ± SEM time to flare was 212/250 ± 9.77 days. Patients with shorter disease duration at enrollment, older age at onset and diagnosis, shorter disease duration prior to experiencing clinically inactive disease, and shorter time from onset of clinically inactive disease to enrollment were found to have significantly lower hazard ratios for likelihood of flare by 8 months (P < 0.05). CONCLUSION: Over one-third of patients with polyarticular JIA with sustained clinically inactive disease will experience a flare by 8 months after discontinuation of anti-TNF therapy. Several predictors of lower likelihood of flare were identified.

Indomethacin therapy effective in a patient with depletion syndrome from secretory villous adenoma.

This paper details the case of a 26-year-old woman with depletion syndrome and the effectiveness of her treatment with indomethacin. Villous adenomas are benign neoplasms with a high incidence of becoming malignant. A small percentage of villous adenomas are known to cause depletion syndrome, also referred to as the McKittrick-Wheelock syndrome, a condition characterised by secretory diarrhoea, dehydration, hyponatremia, hypokalaemia, hypochloraemia, metabolic acidosis and acute renal failure. Prostaglandin-E2 mediates the hypersecretion mechanism observed in depletion syndrome, and can be inhibited by cyclo-oxygenase inhibitors. This case study measured the effectiveness of prostaglandin inhibition on a patient with oral and parenteral electrolyte replacement refractory depletion syndrome. Fluid loss and prostaglandin levels were measured before and after pharmacological treatment. This case demonstrates a 49% decrease in rectal effluent and a marked commensurate decrease in daily replenishment requirements within 48 hours of indomethacin treatment initiation, resulting in subsequent electrolyte stabilisation.

The influence of personal familiarity on object naming, knowledge, and use in dementia.

Reports of semantic dementia patients have shown more accurate identification and use for personal objects than unfamiliar analogs of the same objects (e.g., personal comb versus experimenter's comb) [Bozeat, S., Lambon Ralph, M. A., Patterson, K., & Hodges, J. R. (2002). The influence of personal familiarity and context on object use in semantic dementia. Neurocase, 8, 127-134; Snowden, J. S., Griffiths, H., & Neary, D. (1994). Semantic dementia: Autobiographical contribution to preservation of meaning. Cognitive Neuropsychology, 11, 265-288]. Despite potential clinical implications, the personal object advantage has not been explored in various dementia populations. Sixteen mild to moderate dementia patients were tested with 12-15 of their personal objects and laboratory analog objects. Four tasks were administered: Naming, Gesture, Semantic/Script Generation, and Personal Object Decision (i.e., Is this yours?). Although 25% of the sample performed at chance in identifying personal objects as their own, participants generated more specific information (t=2.3, p=.03) and more accurate gestures (t=2.4, p=.03) for personal objects. Thus, the personal object advantage was observed for script/semantic knowledge and movement sequences, and should be considered in residential planning for various dementia patients.

Neuropsychiatric symptoms and medical illness in patients with dementia: an exploratory study.

OBJECTIVE: To determine the association between neuropsychiatric symptoms and the presence of medical illness among outpatients with mild dementia. METHOD: The Neuropsychiatric Inventory (NPI) was used to assess neuropsychiatric symptoms, and the Cumulative Illness Rating Scale (CIRS) was used to evaluate physical impairment, in 44 outpatients diagnosed as having dementia (Alzheimer disease, n=22; vascular dementia, n=13; mixed dementia, n=9). The tests used were standard parts of a memory assessment program at a college of osteopathic medicine. Pearson product moment correlations were used to assess any associations between NPI and CIRS scores. RESULTS: Significant associations were identified between several NPI-assessed symptoms and degree of medical illness as measured by the CIRS. Neurobehavioral problems were significantly correlated (P<.05) with illness in the following body organ systems: gastrointestinal (lower), genitourinary, neurologic, ophthalmologic/otolaryngologic, psychiatric, and respiratory. CONCLUSION: The authors' preliminary data underscore the importance of primary care physicians assessing patients with dementia for comorbidity of psychiatric illnesses when conducting medical examinations.

Validity of the Medication Administration Test among older adults with and without dementia.

BACKGROUND: Impairments in everyday activities (ie, using the telephone, driving, managing medication) have been associated with increasing age as well as dementia severity. One of the initial functional losses among older adults both with and without dementia is impaired medication self-management skills. In fact, reduced ability to self administer medication has been identified as a significant predictor of an assisted living (AL) placement (vs an independent living [IL] placement) among older adults. We recently developed a Medication Administration Test (MAT) to aid in placement decisions regarding level of care (eg, IL, AL). OBJECTIVE: The purpose of this study was to examine the construct and concurrent validity of the MAT in a sample of older adults residing in a continuing care retirement facility. METHODS: IL and AL participants were administered the MAT along with a brief neuropsychological battery that included the Naturalistic Action Test, the Mini-Mental State Examination, and the Instrumental Activities of Daily Living scale. The construct validity of the MAT was assessed by correlating MAT scores with the other neuropsychological instruments of cognition and function. With respect to the MAT's concurrent validity, a discriminant function analysis was run to determine the classification accuracy (IL vs AL) of the newly developed MAT. RESULTS: Sixty-two white participants were included in the study (mean age, 85.56 years); 34 participants were residing in an AL setting and 28 were residing in an IL setting. Evidence for construct validity was relatively robust, as performance on the MAT was moderately correlated with scores on the Mini-Mental State Examination, the Naturalistic Action Test, and the Instrumental Activities of Daily Living scale. When MAT scores were subjected to a discriminant function analysis to assess concurrent validity, MAT performance accurately classified 79.03% of the participants into the appropriate level of care (IL or AL). CONCLUSION: This project provides preliminary evidence for the validity of the MAT when used for placement decisions within continuing care retirement communities. Given the current need for objective measures to aid in level of care decision making, the MAT may be useful in both clinical and research arenas.

Alternate-form reliability of the Dementia Rating Scale-2.

The Dementia Rating Scale-2 (DRS-2) is a frequently used assessment of cognitive status among older adults in both research and clinical practice. Despite its well-established psychometric properties, its use in serial assessments has posed limitations with regard to practice effects. The primary purpose of the present study is to provide preliminary evidence of alternate-form reliability for the DRS-2. A heterogeneous sample of 52 community-dwelling adults over age 60 with no reported diagnosis of dementia were administered the DRS-2 as well as a newly developed alternate form [DRS-2: AF; Schmidt, K. S. (2004). Dementia Rating Scale-2 Alternate Form: Manual supplement. Lutz, FL: Psychological Assessment Resources]. Our results reveal strong correlations between the two forms; further, no significant differences were found between total scale and subscale scores obtained from the two forms. Therefore, the DRS-2: AF may be a valuable assessment tool in both research and clinical arenas.

Reduced ability to self-administer medication is associated with assisted living placement in a continuing care retirement community.

OBJECTIVE: To examine whether reduced ability to self-administer medication can accurately classify living placement (independent or assisted living) in a continuing care retirement community (CCRC). DESIGN: Convenience sample of consecutive patients seen in a medical clinic. SETTING: An outpatient medical clinic at a CCRC. PARTICIPANTS: A group of 78 consecutive patients (aged 68-98 years) scheduled for a geriatric medical evaluation between May 1, 2001, and August 31, 2001, residing in an independent (IL) or assisted living (AL) apartment. MEASUREMENTS: Ability to self-administer medication was assessed by asking residents to respond to a medication administration question based on a 5-point Likert scale. Residents were also given measures of cognitive status (MMSE), activities of daily living (ADL), and depression (GDS). Further, age of residents as well as number of falls within the previous 6 months were recorded. RESULTS: A discriminant function analysis accurately classified living placement (IL or AL) in 89.7% of the cases based on the ability of residents to self-administer medication. The additions of MMSE score, ADL performance, GDS score, number of falls, and age of the residents to the analyses did not improve the number of cases that were correctly classified. CONCLUSION: Ability to self-administer medication emerged as the main predictor of current living environment within the CCRC in the present study. These results underscore the importance of considering a resident's ability to independently manage his or her medications when placement decisions are being made within CCRCs.

Accuracy and Adequacy of Computed Tomography-Guided Lung Biopsies: Experience From a Community Hospital.

CONTEXT: Small tissue biopsies obtained through minimally invasive methods have become the primary diagnostic tools for the pathologic characterization and testing of lung masses. In view of recent advances in targeted therapy for non-small cell lung carcinoma, and lung adenocarcinoma in particular, pathologists are now expected to thoroughly characterize lung lesions microscopically while making certain that enough tissue remains for potential molecular analysis if indicated. OBJECTIVE: To report our experience with computed tomography (CT)-guided lung needle biopsies with particular concentration on diagnostic yield, diagnostic accuracy, and adequacy of tissue for molecular testing if indicated. METHODS: A retrospective observational study analyzed 224 biopsies in 222 patients undergoing CT-guided lung needle biopsies. Accuracy of diagnosis and adequacy of tissue for molecular testing, if applicable, was evaluated. A standardized protocol for specimen evaluation, triage, and processing was used. This protocol included intraprocedural real-time microscopic specimen evaluation and triage by a pathologist and use of a histologic protocol specifically designed to conserve tissue for ancillary testing. The initial biopsy was considered successful if the specimen was malignant, had specific benign features, or had nonspecific benign features with follow-up supporting benign lesion. Initial biopsy failure cases were those with inadequate tissue or a nonspecific result with highly suspicious imaging or clinical findings. RESULTS: Of the 224 biopsies, 8 cases with benign but nonspecific findings lacked follow-up and were excluded from the study. The biopsy was diagnostically successful in 189 of 216 (88%) cases. Of these 189 cases, 154 (81%) were malignant, and 35 (19%) were benign. There were 28 diagnostic failures. Subsequent tissue sampling of 13 of 28 diagnostic failures found 9 (69%) to be malignant. Molecular studies were requested on 25 cases: 24 had sufficient material for some of the requested tests, and 20 had enough tissue for all requested testing. CONCLUSION: A standardized protocol and team approach for CT-guided lung needle biopsy optimizes the ability to achieve a high accurate diagnostic yield with adequate tissue for molecular testing.