Cognitive dysfunction is present in up to 70% of patients with multiple sclerosis (MS) and has been reported at all stages and in all subtypes of the disease. These deficits have been reported across ...a variety of cognitive domains, but are generally under-recognized and incompletely evaluated in routine clinical practice. The aim of this study was to investigate the spectrum of cognitive impairment in patients with MS presenting to a specialist MS clinic using the Cambridge Neuropsychological Test Automated Battery (CANTAB), administered on a touchscreen platform. Ninety MS patients completed computerized CANTAB tasks assessing working memory, executive function, processing speed, attention, and episodic memory. Scores were adjusted for age, sex, and level of education and classified as normal or impaired based on comparison with a large normative data pool. We also investigated the impact of clinical and demographic variables which could potentially influence cognitive performance including patient educational level (a proxy for cognitive reserve), disease status (duration, course, and severity of MS), and depression. CANTAB testing detected cognitive impairment in 40 patients (44% of the sample). The most frequently impaired domain was executive function, present in 55% of cognitively impaired individuals. Disease duration and severity were significantly associated with performance across various cognitive domains. Patients with depressive symptoms were also more likely to exhibit impaired processing speed. Results from this study confirm that cognitive impairment is common and occurs across a range of domains among MS patients attending routine clinical visits. CANTAB tasks provide a sensitive and practical approach to cognitive testing in MS patients as part of a holistic patient assessment.
For many years, it is not fully understood how non-drainage scleral buckling surgery brings about spontaneous reattachment of the detached retina when retinal breaks remain open at the end of ...surgery. Various explanations have been put forward, but none more interesting than the effect of fluid currents associated with eye movements. One such explanation involved the physics of the Bernoulli's principle. Daniel Bernoulli was an eighteenth century Swiss mathematician and he described an equation based on the conservation of energy. The sum of pressure energy, potential energy and kinetic energy remains constant. Bernoulli's equation usually applies to closed system such as the flow of fluid through pipes. When fluid flows through a constriction, the speed of fluid increases, the kinetic energy increases. If there was no change in elevation (potential energy), then the increase in kinetic energy must be accompanied by a decrease in pressure energy. In ophthalmic surgery, the Bernoulli's effect is the basis for venturi pumps that drive vitrectomy and phacoemulsification machines. This essay expounds on how Bernoulli's effect might be relevant to scleral buckling for retinal detachment repair. In the era when vitrectomy is increasing the primary surgical operation for retinal detachment, the pervasive advice is to emphasise the importance of patient adopting head posture and remaining still postoperatively. The exception is non-drainage scleral buckling surgery. Early postoperative mobilisation may be vital to achieve reattachment.
The aim of the study was to confirm the validity and reliability of the Observation Scheme-12, a measurement tool for rating clinical communication skills.
The study is a sub-study of an intervention ...study using audio recordings to assess the outcome of communication skills training. This paper describes the methods used to validate the assessment tool Observation Scheme-12 by operationalizing the crude 5-point scale into specific elements described in a codebook. Reliability was tested by calculating the intraclass correlation coefficients for interrater and intrarater reliability.
The validation of the Observation Scheme-12 produced a rating tool with 12 items. Each item has 0 to 5 described micro-skills. For each item, the codebook described the criteria for delivering a rating from 0 to 4 depending on how successful the different micro-skills (or number of used jargon words) was accomplished. Testing reliability for the overall score intraclass correlation coefficients was 0.74 for interrater reliability and 0.86 for intrarater reliability. An intraclass correlation coefficient greater than 0.5 was observed for 10 of 12 items.
The development of a codebook as a supplement to the assessment tool Observation Scheme-12 enables an objective rating of audiotaped clinical communication with acceptable reliability. The Observation Scheme-12 can be used to assess communication skills based on the Calgary-Cambridge Guide.
For men with newly diagnosed prostate cancer, we aimed to develop and validate a model to predict the risk of progression on active surveillance (AS), which could inform more personalised AS ...strategies. In total, 883 men from 3 European centres were used for model development and internal validation, and 151 men from a fourth European centre were used for external validation. Men with Cambridge Prognostic Group (CPG) 1-2 disease at diagnosis were eligible. The endpoint was progression to the composite endpoint of CPG3 disease or worse (≥CPG3). Model performance at 4 years was evaluated through discrimination (C-index), calibration plots, and decision curve analysis. The final multivariable model incorporated prostate-specific antigen (PSA), Grade Group, magnetic resonance imaging (MRI) score (Prostate Imaging Reporting & Data System (PI-RADS) or Likert), and prostate volume. Calibration and discrimination were good in both internal validation (C-index 0.742, 95% CI 0.694-0.793) and external validation (C-index 0.845, 95% CI 0.712-0.958). In decision curve analysis, the model offered net benefit compared to a 'follow-all' strategy at risk thresholds of ≥0.08 and ≥0.04 in development and external validation, respectively. In conclusion, our model demonstrated good accuracy and clinical utility in predicting the progression on AS at 4 years post-diagnosis. Men with lower risk predictions could subsequently be offered less-intense surveillance. Further external validation in larger cohorts is now required.
Perinatal audits in the Netherlands showed that stillbirth was nearly always preceded by a period of reduced fetal movements. Patient or caregiver delay was identified as a substandard care factor.
...To determine whether the use of a new information brochure for pregnant women on fetal movements results in less patient delay in contacting their maternity caregiver.
A pre- and post-survey cohort study in the Netherlands, including 140 women in maternity care with a singleton pregnancy, expecting their first child. All participating women filled out a baseline questionnaire, Cambridge Worry Scale and pre-test questionnaire at the gestational age of 22–24 weeks. Subsequently, the intervention group received a newly developed information brochure on fetal movements. At a gestational age of 28 weeks, all women received the post-test questionnaire. Multiple regression analyses were used.
Per-protocol analysis showed less patient delay in the intervention group compared to the control group (Odds Ratio 0.43; 95% Confidence Interval 0.17–0.86, p=0.02). A significant linear relation was observed between reading the information brochure and an increase of knowledge about fetal movements (B=1.2, 95% Confidence Interval 1.0–1.4, p<0.001). Maternal concerns did not affect patient delay to report reduced fetal movements.
Use of an information brochure regarding fetal movements has the potential to reduce patient delay and increase knowledge about reduced fetal movements. A national survey to determine the effect of an information brochure about reduced fetal movements on patient delay and stillbirth rates is needed.
Four groups of the most highly cited scientific articles (46 in total), which either describe the Cambridge Structural Database (CSD) System or report scientific research applications of the CSD, ...have been selected for citation analysis. The analysis has been carried out to study the scientific importance of crystal structure information made available to the international research community via the CSD or via reviews and research articles that make use of the CSD as a primary information source. Two groups, A and B of ten articles each (A published before 1998, and B published post‐1998), are authored by staff of the CCDC, while two further groups, C and D containing ten reviews and 16 research articles, respectively, are authored by external scientific users of CSD information. Citations have been analysed by their number, and in terms of the journals, scientific subject areas and geographical regions from which the citations originate. Between them, the 46 articles have received 44 381 citations with 15 articles cited more than 1000 times. Citations come from a very broad range of journals and subject areas, with chemistry and crystallography being the dominant fields as expected, but with a very significant citation rate from the life sciences, particularly from the USA. In recent years, there has been a major increase in citations arising from south Asia and the Far East, principally from China, India, Malaysia, Pakistan, Japan, Thailand and Taiwan, who together now rival, and sometimes exceed, the citation rates from Europe and the USA. The effect of citations from new journals, particularly Acta Crystallographica Section E: Structure Reports Online, Crystal Growth and Design and CrystEngComm is clearly reflected in the data.
Objectives
Begun in 1939, the Cambridge-Somerville Youth Study (CSYS) is recognized as the first delinquency prevention experiment and the earliest example of a longitudinal–experimental study with ...criminological outcomes. This paper aims to develop a historical understanding of the origins of the study’s research design.
Methods
The present study is guided by the socio-historical approach and informed by past historical research in criminology. It draws upon a wide array of archival records and published works from the late nineteenth century to the present day.
Results
Richard Clarke Cabot designed and directed the CSYS. Major influences on the study’s research design can be traced to Cabot’s medical practice and research, his advocacy for social work practice and research, and his professional relationship with the Gluecks. The beginnings of experimentation in the social sciences during the early twentieth century may have also played a role. Joan McCord’s early involvement in the study proved instrumental to its longitudinal component.
Conclusions
The rigorous and innovative research design of the CSYS marks an important chapter in the history of experimental criminology, and its influence continues to this day. New experimental studies on the prevention of crime and delinquency must continue to strive to advance scientific knowledge and improve public policy.
Specific therapy of ocular infections often requires etiological diagnosis that is a combined effect of observation of characteristic clinical features and microbiological investigations. Clinical ...impression is central to guiding the laboratory investigation, and the aim of laboratory investigation is to confirm or rule out the clinical diagnosis. However, clinical features may vary considerably, and no one clinical feature may be pathognomonic of a particular pathogen. In addition, there may be a racial, geographical, and climatic difference in the distribution and type of causative agents associated with infections. Ophthalmologists have at their disposal in vivo and in vitro methods of diagnosis of ocular infections. The expertise of the clinician and the microbiologist along with the facilities available, determine the success with accurate diagnosis. A wide range of conventional and molecular techniques are available that not only provide rapid diagnosis for known common infections but have the potential to bring to the fore unknown organisms that may be associated with ocular infections.
The characteristics of N-H...O, O-H...O, and C-H...O hydrogen bonds are examined in a group of 28 high-resolution crystal structures of protein-ligand complexes from the Protein Data Bank and ...compared with interactions found in small-molecule crystal structures from the Cambridge Structural Database. It is found that both strong and weak hydrogen bonds are involved in ligand binding. Because of the prevalence of multifurcation, the restrictive geometrical criteria set up for hydrogen bonds in small-molecule crystal structures may need to be relaxed in macromolecular structures. For example, there are definite deviations from linearity for the hydrogen bonds in protein-ligand complexes. The formation of C-H...O hydrogen bonds is influenced by the activation of the C(alpha)-H atoms and by the flexibility of the side-chain atoms. In contrast to small-molecule structures, anticooperative geometries are common in the macromolecular structures studied here, and there is a gradual lengthening as the extent of furcation increases. C-H...O bonds formed by Gly, Phe, and Tyr residues are noteworthy. The numbers of hydrogen bond donors and acceptors agree with Lipinski's "rule of five" that predicts drug-like properties. Hydrogen bonds formed by water are also seen to be relevant in ligand binding. Ligand C-H...O(w) interactions are abundant when compared to N-H...O(w) and O-H...O(w). This suggests that ligands prefer to use their stronger hydrogen bond capabilities for use with the protein residues, leaving the weaker interactions to bind with water. In summary, the interplay between strong and weak interactions in ligand binding possibly leads to a satisfactory enthalpy-entropy balance. The implications of these results to crystallographic refinement and molecular dynamics software are discussed.
Ectopia lentis (EL) is a condition that can either herald underlying systemic conditions, or be isolated. The recent expansion in the genetics of these conditions has furthered the understanding of ...the underlying molecular aetiology. It is becoming apparent that novel genes, and in particular the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family, are important in ocular development. The common link in these genes seems to be EL. The clinical management of EL is challenging. In particular, the options for addressing surgically induced aphakia in the context of an ectopic capsule are varied. Little evidence exists to direct management of these issues. This review summarises the molecular pathogenesis of EL and conditions associated with it, using the genetic aetiology as a framework. Furthermore, it summarises some of the issues involved in its clinical management.
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