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Dopaminergic imaging is an established biomarker for dementia with Lewy bodies, but its diagnostic accuracy at the mild cognitive impairment (MCI) stage remains uncertain.
To provide robust prospective evidence of the diagnostic accuracy of dopaminergic imaging at the MCI stage to either support or refute its inclusion as a biomarker for the diagnosis of MCI with Lewy bodies.
We conducted a prospective diagnostic accuracy study of baseline dopaminergic imaging with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computerised tomography (123I-FP-CIT SPECT) in 144 patients with MCI. Images were rated as normal or abnormal by a panel of experts with access to striatal binding ratio results. Follow-up consensus diagnosis based on the presence of core features of Lewy body disease was used as the reference standard.
At latest assessment (mean 2 years) 61 patients had probable MCI with Lewy bodies, 26 possible MCI with Lewy bodies and 57 MCI due to Alzheimer's disease. The sensitivity of baseline FP-CIT visual rating for probable MCI with Lewy bodies was 66% (95% CI 52–77%), specificity 88% (76–95%) and accuracy 76% (68–84%), with positive likelihood ratio 5.3.
It is over five times as likely for an abnormal scan to be found in probable MCI with Lewy bodies than MCI due to Alzheimer's disease. Dopaminergic imaging appears to be useful at the MCI stage in cases where Lewy body disease is suspected clinically.
Despite efforts to improve maternal and child nutrition, undernutrition remains a major public health challenge in Ghana. The current study explored community perceptions of undernutrition and context-specific interventions that could improve maternal and child nutrition in rural Northern Ghana.
This exploratory qualitative study used ten focus group discussions to gather primary data. The discussions were recorded, transcribed and coded into themes using Nvivo 12 software to aid thematic analysis.
The study was conducted in rural Kassena-Nankana Districts of Northern Ghana.
Thirty-three men and fifty-one women aged 18–50 years were randomly selected from the community.
Most participants reported poverty, lack of irrigated agricultural land and poor harvests as the main barriers to optimal nutrition. To improve maternal and child nutrition, study participants suggested that the construction of dams at the community level would facilitate all year round farming including rearing of animals. Participants perceived that the provision of agricultural materials such as high yield seedlings, pesticides and fertiliser would help boost agricultural productivity. They also recommended community-based nutrition education by trained health volunteers, focused on types of locally produced foods and appropriate ways to prepare them to help improve maternal and child nutrition.
Drawing on these findings and existing literature, we argue that supporting community initiated nutrition interventions such as improved irrigation for dry season farming, provision of agricultural inputs and community education could improve maternal and child nutrition.
Recently published diagnostic criteria for mild cognitive impairment with Lewy bodies (MCI-LB) include five neuropsychiatric supportive features (non-visual hallucinations, systematised delusions, apathy, anxiety and depression). We have previously demonstrated that the presence of two or more of these symptoms differentiates MCI-LB from MCI due to Alzheimer's disease (MCI-AD) with a likelihood ratio >4. The aim of this study was to replicate the findings in an independent cohort.
Participants ⩾60 years old with MCI were recruited. Each participant had a detailed clinical, cognitive and imaging assessment including FP-CIT SPECT and cardiac MIBG. The presence of neuropsychiatric supportive symptoms was determined using the Neuropsychiatric Inventory (NPI). Participants were classified as MCI-AD, possible MCI-LB and probable MCI-LB based on current diagnostic criteria. Participants with possible MCI-LB were excluded from further analysis.
Probable MCI-LB (n = 28) had higher NPI total and distress scores than MCI-AD (n = 30). In total, 59% of MCI-LB had two or more neuropsychiatric supportive symptoms compared with 9% of MCI-AD (likelihood ratio 6.5, p < 0.001). MCI-LB participants also had a significantly greater delayed recall and a lower Trails A:Trails B ratio than MCI-AD.
MCI-LB is associated with significantly greater neuropsychiatric symptoms than MCI-AD. The presence of two or more neuropsychiatric supportive symptoms as defined by MCI-LB diagnostic criteria is highly specific and moderately sensitive for a diagnosis of MCI-LB. The cognitive profile of MCI-LB differs from MCI-AD, with greater executive and lesser memory impairment, but these differences are not sufficient to differentiate MCI-LB from MCI-AD.
Lewy body dementia, consisting of both dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is considerably under-recognised clinically compared with its frequency in autopsy series.
This study investigated the clinical diagnostic pathways of patients with Lewy body dementia to assess if difficulties in diagnosis may be contributing to these differences.
We reviewed the medical notes of 74 people with DLB and 72 with non-DLB dementia matched for age, gender and cognitive performance, together with 38 people with PDD and 35 with Parkinson's disease, matched for age and gender, from two geographically distinct UK regions.
The cases of individuals with DLB took longer to reach a final diagnosis (1.2 v. 0.6 years, P = 0.017), underwent more scans (1.7 v. 1.2, P = 0.002) and had more alternative prior diagnoses (0.8 v. 0.4, P = 0.002), than the cases of those with non-DLB dementia. Individuals diagnosed in one region of the UK had significantly more core features (2.1 v. 1.5, P = 0.007) than those in the other region, and were less likely to have dopamine transporter imaging (P < 0.001). For patients with PDD, more than 1.4 years prior to receiving a dementia diagnosis: 46% (12 of 26) had documented impaired activities of daily living because of cognitive impairment, 57% (16 of 28) had cognitive impairment in multiple domains, with 38% (6 of 16) having both, and 39% (9 of 23) already receiving anti-dementia drugs.
Our results show the pathway to diagnosis of DLB is longer and more complex than for non-DLB dementia. There were also marked differences between regions in the thresholds clinicians adopt for diagnosing DLB and also in the use of dopamine transporter imaging. For PDD, a diagnosis of dementia was delayed well beyond symptom onset and even treatment.
Shanidar Cave in Iraqi Kurdistan became an iconic Palaeolithic site following Ralph Solecki's mid twentieth-century discovery of Neanderthal remains. Solecki argued that some of these individuals had died in rockfalls and—controversially—that others were interred with formal burial rites, including one with flowers. Recent excavations have revealed the articulated upper body of an adult Neanderthal located close to the ‘flower burial’ location—the first articulated Neanderthal discovered in over 25 years. Stratigraphic evidence suggests that the individual was intentionally buried. This new find offers the rare opportunity to investigate Neanderthal mortuary practices utilising modern archaeological techniques.
In response to the global financial crisis, governments around the world took unprecedented measures to avert the collapse of the global economic system. The scale and extent of this State-led intervention in the private sector, using billions of dollars of taxpayers’ money, forced a re-think of prevailing economic orthodoxy in a world of freely moving capital. This new reality presents challenges for investor-State dispute settlement, particularly where international investment law is underdeveloped or where the relationship between international law and international community policy is unclear. Take the 2012 Greek government bond exchange, the largest sovereign debt restructuring in history. It was a condition precedent to Greece receiving a €130 billion bail-out from the Eurozone Member States that private holders of Greek debt accept a 53.5 per cent haircut on the value of their bonds. The restructuring followed international best practice, using collective-action clauses to prevent ‘holdout’ bondholders from refusing to participate in the exchange and suing the State in domestic courts for full repayment under the bond contract. Following this multilateral effort driven by the Eurozone, the European Central Bank and the International Monetary Fund to reduce Greece's debt burden to sustainable levels, holders of restructured bonds commenced investment treaty arbitrations against Greece, arguing that they are entitled to compensation for the haircut under international law.
It is reasonable to expect that such real-world events will have implications for the development of international investment law, particularly as regards host States’ ‘legitimate regulatory interests’, a concept introduced but not defined by the tribunal in Saluka v. Czech Republic. Indeed, the altered global political economy since 2008 is reflected in the current focus on the right of States parties to international investment agreements (IIAs) to enact regulatory measures for the general welfare without incurring liability to foreign investors. This is now widely described as the State's ‘right to regulate’.
Mindful of this recent history, the purpose of this chapter is to survey how Contracting Parties to IIAs are reasserting their right to regulate in investment arbitration proceedings and in the drafting of their IIAs. This trend precedes the global financial crisis. In 2004, Canada and the United States both substantially reformulated their model bilateral investment treaties (BITs) to reflect concerns that some tribunals had interpreted IIAs too much in favour of investor rights at the expense of host States’ regulatory sovereignty.
The paper reports the preliminary results from the short season of fieldwork that the Cyrenaican Prehistory Project was able to undertake with a small Anglo-Libyan team in September 2013. The work concentrated on continuing the excavation of Trench M down the southern side of the Middle Trench and of Trench D on the southern side of the Deep Sounding below it, the eventual objective being to link these so as to provide a high quality dataset of sedimentary and cultural data from the top to the bottom of the Pleistocene occupation deposit (some 12 m). The ~1 m of sediments investigated in Trench M in the 2013 fieldwork includes carbonate crusts possibly formed in oscillating sub-humid to arid climatic pulses, perhaps likely during Marine Isotope Stage (MIS) 4, around 60,000–70,000 years ago. One of these crusts formed the base on which a hearth-like structure had been built. In Trench D evidence for human occupation appears to decline moving up the profile, coinciding with sedimentary evidence of more frequent disruptive climatic events possibly associated with latter stages of MIS 5.
The paper reports on the fifth (2012) season of fieldwork of the Cyrenaican Prehistory Project. The primary focus of the season was the continuation of the excavation of the prehistoric occupation layers in the Haua Fteah cave. A small trench (Trench U) was cut into Holocene (Neolithic) sediments exposed on the south wall of Charles McBurney's Upper Trench. Below this, the excavation of Trench M was continued, on the southern side of McBurney's Middle Trench. In previous seasons we had excavated Oranian ‘Epipalaeolithic’ layers dating to c. 18,000–10,000 BP (years before the present). In 2012 the excavation continued downwards through Dabban ‘Upper Palaeolithic’ occupation layers, one of which was associated with a post-built structure and likely hearths. There are indications of an occupational hiatus separating the oldest Dabban from the youngest Levallois-Mousterian (Middle Palaeolithic or Middle Stone Age) lithic material. The Deep Sounding excavated by Charles McBurney in 1955 was cleared of backfill to its base, and its south-facing wall was recorded in detail and sampled extensively for materials for dating and palaeoenvironmental reconstruction. McBurney believed that he had reached bedrock at the base of the Deep Sounding, but a small sounding (Trench S) cut into the sediments below this level found further, albeit sparse, evidence for human occupation. Whilst the antiquity of ‘Pre-Aurignacian’ human occupation at the site still needs to be resolved, it seems likely to reach back at least to Marine Isotope Stage 5e, the beginning of the last interglacial (c. 130,000–115,000 BP). Important finds from the 2012 excavations in terms of the behavioural complexity of the human groups using the cave include a possible worked bone point from a Pre-Aurignacian layer and a granite rubbing stone in a Dabban layer from a source over 600 km from the cave.
A range of new Tubercul ns prepared from extracts of living organisms belonging to 12 mycobacterial species has been used to assess the effect of BCG immunization and contact with environmental mycobacteria on Ugandan adults. A total of 2,456 tests were carried out on 562 people, 86% of whom came from three areas selected for special study. These areas were chosen on the basis of occurrence of leprosy and M. ulcerans infection and on data concerning the distribution of environmental mycobacteria. It was found that the effect of BCG was small compared with that previously observed amongst Kenyan schoolchildren, but that the effect of geographical origin was considerable. There was some correlation between the percentages of reactivity to the reagents and the frequency of mycobacteria in the environment.
The FRCS Orth examination is generally considered to be fair although very searching and stressful. It is a major obstacle and hurdle to negotiate during higher specialist orthopaedic training. The syllabus is very broad and so the examiners can ask anything they really want to. About 6–12 months of hard work will be required beforehand if you wish to face the examiners with some degree of confidence over the green baize table.
The aims of the examination are to see if you have sufficient knowledge to become a consultant orthopaedic surgeon and be able to practise safely. Much of the examination can be passed with the knowledge and skills acquired during everyday training, unfortunately it does have to be backed up with a broad knowledge base. The written paper is now referred to as section I and the clinicals and orals as section II. The written paper is now a separate examination held several weeks before the clinicals and orals. The written paper format has been changed to multiple choice questions (MCQs) and extended matching item questions (EMIs) and has to be successfully passed before a candidate is allowed to sit the clinicals and orals. The MCQ/EMI paper is regarded as more difficult to pass than the old style written paper as it tests a much larger breadth and depth of orthopaedics.
The FRCS Orth examination will definitely test you on aspects of basic science – in the past there has commonly been a surgical approach question in the written paper, and although the format is changing it is highly likely that the emphasis and content of questions will not. Critical appraisal of a journal article will remain a part of the revised examination and will require a working knowledge of statistics.
The Basic Science Oral is often feared by candidates, but having established that there is no avoiding it, the key to understanding basic science in orthopaedics and to making it stick in your head is to keep it clinically relevant and to concentrate on understanding concepts rather than learning lists of esoteric facts.
The Basic Science section of the syllabus includes the following headings:
Physiology, biochemistry and genetics
Biomechanics and bioengineering
Bone and joint diseases
Metabolic bone diseases
Rheumatoid arthritis and other arthropathies (inflammatory, crystal, etc.)
Inherited musculoskeletal disorders
Neuromuscular disorders – inherited and acquired
Bone and soft-tissue sarcomas
Infection, thromboembolism and pain
Prosthetics and orthotics
Research and audit
This section of the guide will take you through areas that are commonly tested from the above list. The content cannot be comprehensive; you should check through the above list after reading this chapter and identify areas of weakness in your knowledge that remain.
Anatomy will not be covered here as it is a topic well dealt with in other revision texts.