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.
Dislocation-mediated plasticity in stable nanocrystalline metals, where grain boundary motion is suppressed, is revisited in the context of dislocation elastodynamics. The effect of transient waves that emanate from the generation and motion of dislocations is quantified for an idealized Cu–10 at.% Ta system with grain sizes on the order of 50 nanometers. Simulations indicate that for this material, as dislocation velocities approach 0.6–0.8 times the shear wave speed, grains several grain diameters away from the initial glide event experience a large transient shear stress for a finite duration. These transient shear stresses increase with increasing glide velocity and can activate nucleation sites far from the original nucleation event. These considerations are used to explain recent experimental observations of a lack of increase in flow stress with increasing loading rate, as well as localization resistance, in this class of stable nanocrystalline metals.
Dopaminergic imaging has high diagnostic accuracy for dementia with Lewy bodies (DLB) at the dementia stage. We report the first investigation of dopaminergic imaging at the prodromal stage.
We recruited 75 patients over 60 with mild cognitive impairment (MCI), 33 with probable MCI with Lewy body disease (MCI-LB), 15 with possible MCI-LB and 27 with MCI with Alzheimer's disease. All underwent detailed clinical, neurological and neuropsychological assessments and FP-CIT [123I-N-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)] dopaminergic imaging. FP-CIT scans were blindly rated by a consensus panel and classified as normal or abnormal.
The sensitivity of visually rated FP-CIT imaging to detect combined possible or probable MCI-LB was 54.2% [95% confidence interval (CI) 39.2–68.6], with a specificity of 89.0% (95% CI 70.8–97.6) and a likelihood ratio for MCI-LB of 4.9, indicating that FP-CIT may be a clinically important test in MCI where any characteristic symptoms of Lewy body (LB) disease are present. The sensitivity in probable MCI-LB was 61.0% (95% CI 42.5–77.4) and in possible MCI-LB was 40.0% (95% CI 16.4–67.7).
Dopaminergic imaging had high specificity at the pre-dementia stage and gave a clinically important increase in diagnostic confidence and so should be considered in all patients with MCI who have any of the diagnostic symptoms of DLB. As expected, the sensitivity was lower in MCI-LB than in established DLB, although over 50% still had an abnormal scan. Accurate diagnosis of LB disease is important to enable early optimal treatment for LB symptoms.
The accurate clinical characterisation of mild cognitive impairment (MCI) is becoming increasingly important. The aim of this study was to compare the neuropsychiatric symptoms and cognitive profile of MCI with Lewy bodies (MCI-LB) with Alzheimer's disease MCI (MCI-AD).
Participants were ⩾60 years old with MCI. Each had a thorough clinical and neuropsychological assessment and 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single photon emission computed tomography FP-CIT SPECT). MCI-LB was diagnosed if two or more diagnostic features of dementia with Lewy bodies were present (visual hallucinations, cognitive fluctuations, motor parkinsonism, rapid eye movement sleep behaviour disorder or positive FP-CIT SPECT). A Lewy body Neuropsychiatric Supportive Symptom Count (LBNSSC) was calculated based on the presence or absence of the supportive neuropsychiatric symptoms defined by the 2017 DLB diagnostic criteria: non-visual hallucinations, delusions, anxiety, depression and apathy.
MCI-LB (n = 41) had a higher LBNSSC than MCI-AD (n = 24; 1.8 ± 1.1 v. 0.7 ± 0.9, p = 0.001). 67% of MCI-LB had two or more of those symptoms, compared with 16% of MCI-AD (Likelihood ratio = 4.2, p < 0.001). MCI-LB subjects scored lower on tests of attention, visuospatial function and verbal fluency. However, cognitive test scores alone did not accurately differentiate MCI-LB from MCI-AD.
MCI-LB is associated with neuropsychiatric symptoms and a cognitive profile similar to established DLB. This supports the concept of identifying MCI-LB based on the presence of core diagnostic features of DLB and abnormal FP-CIT SPECT imaging. The presence of supportive neuropsychiatric clinical features identified in the 2017 DLB diagnostic criteria was helpful in differentiating between MCI-LB and MCI-AD.
Imaging biomarkers for Alzheimer's disease include medial temporal lobe
atrophy (MTLA) depicted on computed tomography (CT) or magnetic resonance
imaging (MRI) and patterns of reduced metabolism on fluorodeoxyglucose
positron emission tomography (FDG-PET).
To investigate whether MTLA on head CT predicts the diagnostic usefulness
of an additional FDG-PET scan.
Participants had a clinical diagnosis of Alzheimer's disease
(n = 37) or dementia with Lewy bodies (DLB;
n = 30) or were similarly aged controls
(n = 30). We visually rated MTLA on coronally
reconstructed CT scans and, separately and blind to CT ratings, abnormal
appearances on FDG-PET scans.
Using a pre-defined cut-off of MTLA ⩾5 on the Scheltens (0–8) scale, 0/30
controls, 6/30 DLB and 23/30 Alzheimer's disease had marked MTLA. FDG-PET
performed well for diagnosing Alzheimer's disease v. DLB
in the low-MTLA group (sensitivity/specificity of 71%/79%), but in the
high-MTLA group diagnostic performance of FDG-PET was not better than
In the presence of a high degree of MTLA, the most likely diagnosis is
Alzheimer's disease, and an FDG-PET scan will probably not provide
significant diagnostic information. However, in cases without MTLA, if
the diagnosis is unclear, an FDG-PET scan may provide additional
clinically useful diagnostic information.
There is a paucity of data on the effect of preterm birth on the immunological composition of breast milk throughout the different stages of lactation. We aimed to characterise the effects of preterm birth on the levels of immune factors in milk during the 1st month postpartum, to determine whether preterm milk is deficient in antimicrobial factors. Colostrum (days 2–5 postpartum), transitional milk (days 8–12) and mature milk (days 26–30) were collected from mothers of extremely preterm (<28 weeks of gestation, n 15), very preterm (28–<32 weeks of gestation, n 15), moderately preterm (32–<37 weeks of gestation, n 15) and term infants (37–41 weeks of gestation, n 15). Total protein, lactoferrin, secretory IgA, soluble CD14 receptor (sCD14), transforming growth factor-β2 (TGF-β2), α defensin 5 (HD5), β defensins 1 (HBD1) and 2, IL-6, IL-10, IL-13, interferon-γ, TNF-α and lysozyme (LZ) were quantified in milk. We examined the effects of lactation stage, gestational age, volume of milk expressed, mode of delivery, parity and maternal infection on milk immune factor concentrations using repeated-measures regression analysis. The concentrations of all factors except LZ and HD5 decreased over the 1st month postpartum. Extremely preterm mothers had significantly higher concentrations of HBD1 and TGF-β2 in colostrum than term mothers did. After controlling for other variables in regression analyses, preterm birth was associated with higher concentrations of HBD1, LZ and sCD14 in milk samples. In conclusion, preterm breast milk contains significantly higher concentrations of some immune proteins than term breast milk.
We assessed evidence of exposure to viruses and bacteria in an unmanaged and long-isolated population of Soay sheep (Ovis aries) inhabiting Hirta, in the St Kilda archipelago, 65 km west of Benbecula in the Outer Hebrides of Scotland. The sheep harbour many metazoan and protozoan parasites but their exposure to viral and bacterial pathogens is unknown. We tested for herpes viral DNA in leucocytes and found that 21 of 42 tested sheep were infected with ovine herpesvirus 2 (OHV-2). We also tested 750 plasma samples collected between 1997 and 2010 for evidence of exposure to seven other viral and bacterial agents common in domestic Scottish sheep. We found evidence of exposure to Leptospira spp., with overall seroprevalence of 6·5%. However, serological evidence indicated that the population had not been exposed to border disease, parainfluenza, maedi-visna, or orf viruses, nor to Chlamydia abortus. Some sheep tested positive for antibodies against Mycobacterium avium subsp. paratuberculosis (MAP) but, in the absence of retrospective faecal samples, the presence of this infection could not be confirmed. The roles of importation, the pathogen–host interaction, nematode co-infection and local transmission warrant future investigation, to elucidate the transmission ecology and fitness effects of the few viral and bacterial pathogens on Hirta.
Iodine-129 is a high-yield fission product formed in nuclear reactors and is a risk-driving radionuclide in both contaminated land and radioactive waste disposal due to its high mobility and long half-life. Here, the bioreduction behaviour of iodate was investigated by tracking iodine speciation and concentration in solution during the development of progressive anoxia in sediment microcosm experiments incubated at neutral pH. Experiments with acetate added as an electron donor showed the expected cascade of terminal electron-accepting processes. Analysis of solution chemistry showed reduction of iodate to iodide during the early stages of metal (Mn(IV) and Fe(III)) reduction, but with no significant retention of iodine species on solids. There was, however, a net release of natural iodine associated with the sediments to solution when robust iron reduction / sulfate reduction had developed. In addition, over 210 days, the controls with no electron donor and the sterile controls showed no Mn(IV) or Fe(III) reduction but displayed modest sorption of iodate to the sediments in the absence of bioreduction. Overall these results show that under oxic conditions iodate may be partially sorbed to sediments over extended periods but that development of mildly reducing conditions leads to the reductive release of iodine to solution as iodide.
In Australia, hepatitis B (HBV) vaccination is recommended for injecting drug users (IDUs), Indigenous adults and prisoners. We compared immunity to HBV in prisoners and the general population obtained from national serosurveys in 2007. Individuals with HBV surface antibody (HBsAb) positive sera were considered immune from past infection [HBV core antibody (HBcAb) positive] or from vaccination (HBcAb negative). Male prisoners aged 18–58 years had a higher HBsAb seroprevalence than the general population (46·4% vs. 39·4%, P = 0·061). Comparison of HBcAb results was possible for males aged 18–29 years. In this group, higher HBsAb seroprevalence was due to past infection (12·9% vs. 3·0%, P < 0·001), rather than vaccine-conferred immunity (35·3% vs. 43·4%, P = 0·097). All prisoner groups, but especially IDUs, those of Indigenous heritage or those with a previous episode of imprisonment had higher levels of immunity from past infection than the general population (19·3%, 33·0%, 17·1%, respectively, vs. 3·0%, P < 0·05). Indigenous prisoners, non-IDUs and first-time entrants had significantly lower levels of vaccine-conferred immunity than the general population (26·4%, 26·2% and 20·7% respectively vs. 43·4%, P < 0·05). Improving prison-based HBV vaccination would prevent transmission in the prison setting and protect vulnerable members of the community who are at high risk of both infection and entering the prison system.
To systematically summarise the peer-reviewed literature relating to the aetiology, clinical presentation, investigation and treatment of geniculate neuralgia.
Articles published in English between 1932 and 2012, identified using Medline, Embase and Cochrane databases.
The search terms ‘geniculate neuralgia’, ‘nervus intermedius neuralgia’, ‘facial pain’, ‘otalgia’ and ‘neuralgia’ were used to identify relevant papers.
Fewer than 150 reported cases were published in English between 1932 and 2012. The aetiology of the condition remains unknown, and clinical presentation varies. Non-neuralgic causes of otalgia should always be excluded by a thorough clinical examination, audiological assessment and radiological investigations before making a diagnosis of geniculate neuralgia. Conservative medical treatment is always the first-line therapy. Surgical treatment should be offered if medical treatment fails. The two commonest surgical options are transection of the nervus intermedius, and microvascular decompression of the nerve at the nerve root entry zone of the brainstem. However, extracranial intratemporal division of the cutaneous branches of the facial nerve may offer a safer and similarly effective treatment.
The response to medical treatment for this condition varies between individuals. The long-term outcomes of surgery remain unknown because of limited data.
The emergence of invasive fungal wound infections (IFIs) in combat casualties led to development of a combat trauma-specific IFI case definition and classification. Prospective data were collected from 1133 US military personnel injured in Afghanistan (June 2009–August 2011). The IFI rates ranged from 0·2% to 11·7% among ward and intensive care unit admissions, respectively (6·8% overall). Seventy-seven IFI cases were classified as proven/probable (n = 54) and possible/unclassifiable (n = 23) and compared in a case-case analysis. There was no difference in clinical characteristics between the proven/probable and possible/unclassifiable cases. Possible IFI cases had shorter time to diagnosis (P = 0·02) and initiation of antifungal therapy (P = 0·05) and fewer operative visits (P = 0·002) compared to proven/probable cases, but clinical outcomes were similar between the groups. Although the trauma-related IFI classification scheme did not provide prognostic information, it is an effective tool for clinical and epidemiological surveillance and research.
Community-onset methicillin resistant Staphylococcus aureus (CO-MRSA) became a prominent cause of infection in North America in 2003, with a peak in the epidemic noted by multiple groups in the USA between 2005 and 2007. We reviewed rates of MRSA in two hospitals in Vancouver, Canada, to observe changes in epidemiology from 2003 to 2011. Episodes of emergency department (ED) MRSA bacteraemia and wounds were extracted from the laboratory database, with rates calculated per 10 000 ED visits. All cases were assumed to be community onset, as they were diagnosed in the ED. A peak in ED MRSA bacteraemias occurred in 2005, at 7·8/10 000 ED visits. By 2011, rates of ED bacteraemia declined significantly to 3·3/10 000 ED visits (P⩽0·03). MRSA wound rates peaked at 82·2 cases/10 000 ED visits in 2007 with a subsequent significant decline to 34·3 cases in 2011 (P = 0·04). We have demonstrated a significant decline in CO-MRSA within our population, consistent with reports from the USA, suggesting a substantial change in the epidemiology of CO-MRSA in certain North American cities.
Little is known about how the rates and characteristics of mental health service users in unpaid work, training and study compare with those in paid employment.
From staff report and patient records, 1353 mental health service users of seven Community Mental Health Teams in two London boroughs were categorized as in paid work, unpaid vocational activity or no vocational activity. Types of work were described using Standard Occupational Classifications. The characteristics of each group were reported and associations with vocational status were explored.
Of the sample, 5.5% were in paid work and 12.7% were in unpaid vocational activity, (including 5.3% in voluntary work and 8.1% in study or training). People in paid work were engaged in a broader range of occupations than those in voluntary work and most in paid work (58.5%) worked part-time. Younger age and high educational attainment characterized both groups. Having sustained previous employment was most strongly associated with being in paid work.
Rates of vocational activity were very low. Results did not suggest a clear clinical distinction between those in paid and unpaid activity. The motivations for and functions of unpaid work need further research.