Good performance of p16/ki‐67 dual‐stained cytology for surveillance of women treated for high‐grade CIN

Women treated for high‐grade cervical intraepithelial neoplasia (CIN) are at risk of recurrent CIN Grade 2 or worse (rCIN2+). Currently, posttreatment monitoring is performed using cytology or cytology/high‐risk (hr)HPV cotesting. This study aimed to evaluate the performance of p16/Ki‐67 dual‐stained cytology (p16/Ki‐67) for posttreatment monitoring. Three hundred and twenty‐three women treated for high‐grade CIN in the SIMONATH study underwent close surveillance by cytology, hrHPV and DNA methylation marker testing up to 12 months posttreatment. Histological endpoints were ascertained by colposcopy with biopsy at 6 and/or 12 months. p16/Ki‐67 dual‐staining was performed on residual liquid‐based cytology samples obtained at, or shortly before biopsy collection. Clinical performance estimates of cytology, hrHPV, p16/Ki‐67 testing and combinations thereof for the detection of rCIN2+ were determined and compared to each other. Sensitivity of p16/Ki‐67 for rCIN2+ (69.2%) was nonsignificantly lower than that of cytology (82.1%; ratio 0.84, 95% CI: 0.71–1.01), but significantly lower than that of hrHPV testing (84.6%; ratio 0.82, 95% CI: 0.68–0.99). Specificity of p16/Ki‐67 for rCIN2+ (90.4%) was significantly higher compared to both cytology (70.8%; ratio 1.28, 95% CI: 1.19–1.37) and hrHPV testing (76.2%; ratio 1.19, 95% CI: 1.12–1.26). Overall, hrHPV testing showed very high sensitivity, along with a good specificity. When considering cotesting, combined p16/Ki‐67/hrHPV testing showed rCIN2+ sensitivity comparable to cytology/hrHPV cotesting (87.2% vs. 89.7%; ratio 0.97, 95% CI: 0.92–1.03), but with significantly increased specificity (74.2% vs. 58.1%; ratio 1.28, 95% CI: 1.19–1.38). Thus, when considered in combination with hrHPV, p16/Ki‐67 might be an attractive approach for surveillance of women treated for high‐grade CIN.     

Optimizing the human learnability of abstract network representations

Precisely how humans process relational patterns of information in knowledge, language, music, and society is not well understood. Prior work in the field of statistical learning has demonstrated that humans process such information by building internal models of the underlying network structure. However, these mental maps are often inaccurate due to limitations in human information processing. The existence of such limitations raises clear questions: Given a target network that one wishes for a human to learn, what network should one present to the human? Should one simply present the target network as-is, or should one emphasize certain parts of the network to proactively mitigate expected errors in learning? To investigate these questions, we study the optimization of network learnability in a computational model of human learning. Evaluating an array of synthetic and real-world networks, we find that learnability is enhanced by reinforcing connections within modules or clusters. In contrast, when networks contain significant core–periphery structure, we find that learnability is best optimized by reinforcing peripheral edges between low-degree nodes. Overall, our findings suggest that the accuracy of human network learning can be systematically enhanced by targeted emphasis and de-emphasis of prescribed sectors of information.

From a young age, humans demonstrate the capacity to learn the relationships between concepts (1–3). During the learning process, humans are exposed to discrete chunks of information that combine and interconnect to form cognitive maps that can be represented as complex networks (4–9). These chunks of information often appear in a natural sequential order, such as words in language, notes in music, and abstract concepts in stories and classroom lectures (10–14). Further, these sequences are encoded in the brain as networks, with links between items reflecting observed transitions (see refs. 15–18 for empirical studies and 19 for a recent review). Broadly, the fact that many different types of information exhibit temporal order (and therefore network structure) motivates investigations into the processes that underlie the human learning of transition networks (8, 19, 20).To understand the network-learning process, recent studies have investigated how humans internally construct abstract representations of associations (21–23). Using a variety of approaches, from computational models to artificial neural networks, such studies have consistently found that the mind builds network representations by integrating information over time. Such integration enables humans to compress exact sequences of experienced events into broader, but less precise, representations of context (24). These mental representations allow learners to make better generalizations about new information, at the cost of accuracy (22). Here, we focus on one particular modeling approach that accounts for the temporal integration and inaccuracies inherent in human learning. In particular, we build upon a maximum-entropy model, which posits that the mind learns a network representation of the world in a manner guided by a tradeoff between accuracy and complexity (21, 25). Specifically, in order to conserve mental resources, humans will tend to reduce the complexity of their representations at the cost of accuracy by allowing for errors during the learning process.While inaccuracies in human learning can aid flexibility across contexts, they present fundamental obstacles for the human comprehension of transition networks. Thus, a clear question emerges: What strategies should be employed to most effectively communicate the structure of a network to an inaccurate human learner? Prior studies of animal communication and behavior have demonstrated the utility of exaggerating the presentation of certain signals to receivers in offsetting erroneous information processing (26, 27). Similarly, one could imagine that, by emphasizing some features of a network over others, one may be able to correct for errors in human learning. Such an approach of targeted modulation of emphasis may be helpful not only in learning a whole network, but also in optimally learning particularly challenging parts of a network. In fact, humans show consistent difficulties in learning certain motifs in networks, such as the connections between modules (21, 28–30). Taken together, these observations suggest that disproportionately weighting specific network features that are difficult to learn may facilitate human network learning.     

Peripheral and central hearing impairment and their relationship with cognition: a review

Objective: To consider the relationships between both peripheral and central hearing impairment and cognition.

Design: Narrative review.

Study sample: Numerous studies exploring the relationship between hearing impairment and cognitive function, particularly in an older population.

Results: In addition to the well-documented relationship between peripheral hearing loss and cognition highlighted in previous comprehensive reviews, there is also some evidence to suggest that there is a relationship between central hearing impairment and cognition. Further research is required to better understand this relationship and its effects on hearing aid benefit in people with both peripheral hearing loss and central hearing impairment.

Conclusions: To fully understand the relationship between hearing impairment and cognitive impairment, not only peripheral but central hearing needs to be considered. Such knowledge could be of benefit in the clinical management of people with both peripheral hearing loss and central hearing impairment.     

Comparison of different endophthalmitis prophylactic measures in cataract surgery - An analysis of 2.4 lakh cases

Purpose:To compare different endophthalmitis prophylaxis methods adopted in cataract surgery (manual small-incision cataract surgery and phacoemulsification) between the years 2013 and 2021 in the community eye care section of a tertiary eye care hospital in South India and report their outcomes.Methods:All cataract surgeries performed from January 2013 to December 2021 (2,46,874 surgeries) at a single center were included in this retrospective study. The different endophthalmitis rates with each regimen were analyzed and evaluated.Results:70,081 surgeries were performed from January 2013 to February 2015, where Tobramycin was added to Balanced Salt Solution (BSS) (Group A). From March 2015 to January 2017, 63,245 surgeries were performed when intracameral Moxifloxacin was given (Group B). From February 2017 to December 2021, 1,13,548 surgeries were performed were Amikacin was added to BSS (Group C). In total, 42 cases of postoperative endophthalmitis were reported during the study period (0.02%). There was no significant difference in the endophthalmitis rates between groups A and B (P = 0.4152); however, there was a significant decrease in endophthalmitis rates in group C when compared with group A (P = 0.04) and group B (P = 0.006).Conclusion:There was a significant reduction in the rates of endophthalmitis following the addition of amikacin in irrigating BSS. Nocardia was one of the predominant organisms isolated from these endophthalmitis patients. This is the first single-center study to report a comparative analysis of different endophthalmitis prophylactic measures in a community eye care set up with a high incidence of Nocardia endophthalmitis prevented with amikacin in BSS irrigating solution.     

Efficacy of erenumab and factors predicting response after 3 months in treatment resistant chronic migraine: a clinical service evaluation

BackgroundCalcitonin gene-related peptide (CGRP) inhibitors have been developed as options for treatment of chronic and episodic migraine. We present our experience of the use of erenumab in a tertiary headache centre.MethodsThis was a prospective clinical audit of all patients commenced on erenumab following a locally agreed pathway and criteria over a consecutive period. Patients received monthly erenumab 140 mg for 3 months. Data were collected prospectively at baseline and 3 months follow up.ResultsOne hundred three patients were commenced on erenumab during the study period. Patients had tried a median of 7 previous prophylactics, including onabotulinum toxin A in 94%. At 3 months there was a reduction in median total (28 to 20, 29% reduction, p < 0.0001) and severe (15 to 5, 67% reduction, p < 0.0001) headache days. 39.8% of patients achieved at least a 30% reduction in total headache days; 61.8% of patients achieved at least a 50% reduction in severe headache days. Meeting either of these thresholds was considered a positive response, 68% of patients achieved this. Presence of daily headache pattern was negatively associated with response, (56% response vs. 90% without daily headache, p = 0.0003). There was no association between age, gender, presence of medication overuse or number of previously tried prophylactic treatments and response to erenumab. 43% of patients reported at least one adverse effect, most commonly constipation (26%); treatment was discontinued in 3 patients due to adverse effects.ConclusionsErenumab was an effective treatment for chronic migraine in this treatment resistant population over 3 months of follow up. Presence of daily headache predicted poorer response but there was still a significant positive response rate in this group.     

Earlier chronotype in patients with rheumatoid arthritis

Clinical Rheumatology - Rheumatoid arthritis (RA) patients show an earlier circadian rhythm (i.e. serum melatonin peaks earlier during the night, indicating an earlier timing of the internal...     

Hiding Lipid Presentation: Viral Interference with CD1d-Restricted Invariant Natural Killer T (iNKT) Cell Activation

The immune system plays a major role in protecting the host against viral infection. Rapid initial protection is conveyed by innate immune cells, while adaptive immunity (including T lymphocytes) requires several days to develop, yet provides high specificity and long-lasting memory. Invariant natural killer T (iNKT) cells are an unusual subset of T lymphocytes, expressing a semi-invariant T cell receptor together with markers of the innate NK cell lineage. Activated iNKT cells can exert direct cytolysis and can rapidly release a variety of immune-polarizing cytokines, thereby regulating the ensuing adaptive immune response. iNKT cells recognize lipids in the context of the antigen-presenting molecule CD1d. Intriguingly, CD1d-restricted iNKT cells appear to play a critical role in anti-viral defense: increased susceptibility to disseminated viral infections is observed both in patients with iNKT cell deficiency as well as in CD1d- and iNKT cell-deficient mice. Moreover, viruses have recently been found to use sophisticated strategies to withstand iNKT cell-mediated elimination. This review focuses on CD1d-restricted lipid presentation and the strategies viruses deploy to subvert this pathway.     

Atraumatic bilateral scapular spine fracture several months after bilateral reverse total shoulder arthroplasty

We report an 89-year-old woman with bilateral atraumatic scapular spine fracture several months after bilateral reverse total shoulder arthroplasty (RTSA). Recently, RTSA has gained popularity in the surgical treatment of complex shoulder disorders such as cuff tear arthropathy. However, scapular fractures may occur several months after surgery as a late complication of this procedure. In this case report we focus on a relatively uncommon subtype, the scapular spine fracture. Although well-known in the orthopedic literature, radiologists are less familiar with this complication. To the best of our knowledge, bilateral scapular fractures have not yet been reported.