How robust are clinical trials in primary and secondary ankle sprain prevention?

OBJECTIVES: Determine the statistical stability of RCTs examining primary and secondary prevention of ankle sprains. METHODS: Databases were searched to August 2023. We included parallel design RCTs, using conservative interventions for preventing ankle sprain, reporting dichotomous injury event outcomes. Statistical stability was quantified using Fragility Index (FI) and Fragility Quotient (FQ). Subgroup analyses were undertaken to test if FI varied based on by study objective, original approach to analysis (frequency vs time to event), follow-up duration, and pre-registration. RESULTS: 3559 studies were screened with 45 RCTs included. The median number of events required to change the statistical significance (FI) was 4 (IQR 1-6). FI was similar regardless of study objective, original analysis, follow-up duration, and pre-registration status. Median (IQR) FQ was 0.015 (0.005-0.046), therefore reversing events <2 patients/100 would alter significance. In 80% of studies the number of patients lost to follow-up was greater than the FI. CONCLUSION: RCTs informing primary and secondary prevention of ankle sprain are fragile. Only a small percentage of outcome event reversals would reverse study significance, and this is often exceeded by the number of drop outs. Robust reporting of dichotomous outcomes requires the use P values and key metrics such as FI or FQ.

Back to the Roots: Agrobacterium-Specific Phages Show Potential to Disinfect Nutrient Solution from Hydroponic Greenhouses.

Agrobacterium biovar 1 is a soilborne plant pathogen with the ability to colonize the irrigation system of greenhouses, causing hairy root disease (HRD). Currently, management focuses on using hydrogen peroxide to disinfect the nutrient solution, but due to the emergence of resistant strains, its efficacy and sustainability are questioned. Using a relevant collection of pathogenic Agrobacterium biovar 1 strains, OLIVR1 to 6, six phages specific to this pathogen and belonging to three different genera were isolated from Agrobacterium biovar 1-infected greenhouses. All phages were named OLIVR, referring to their location of isolation, Onze-Lieve-Vrouwe-Waver, and were characterized by whole-genome analysis, confirming their strictly lytic lifestyle. They remained stable under greenhouse-relevant conditions. To assess the efficacy of the phages, their ability to disinfect greenhouse nutrient solution inoculated with agrobacteria was tested. Each of the phages infected their host, but their ability to decrease the bacterial concentration differed. For instance, OLIVR1 reduced the bacterial concentration with 4 log units without phage resistance emerging. While OLIVR4 and OLIVR5 were also infectious in nutrient solution, they did not always decrease the bacterial load below the limit of detection, and phage resistance emerged. Finally, the mutations causing phage resistance by receptor modification were identified. For OLIVR4-resistant Agrobacterium isolates, but not for OLIVR5-resistant isolates, motility decreased. Together, these data show the potential of some of these phages as disinfectant of nutrient solution, and they might be a valuable tool to tackle HRD. IMPORTANCE Hairy root disease, caused by rhizogenic Agrobacterium biovar 1 is a rapidly emerging bacterial disease worldwide. It affects tomatoes, cucumbers, eggplant, and bell pepper, causing high yield losses in hydroponic greenhouses. Recent findings suggest that the current management practices, mainly focusing on UV-C and hydrogen peroxide to disinfect contaminated water, have a questionable efficacy. Hence, we investigate the potential of phages as a biological means of preventing this disease. Using a diverse collection of Agrobacterium biovar 1, we isolated three different phage species that together infect 75% of the collection. Since these phages are strictly lytic, while remaining both stable and infectious under greenhouse-relevant conditions, they might be suitable candidates for biological control.

Draft Genome Sequences of 27 Rhizogenic Agrobacterium Biovar 1 Strains, the Causative Agent of Hairy Root Disease.

Rhizogenic Agrobacterium biovar 1 strains are important plant pathogens that cause hairy root disease in Cucurbitaceae and Solanaceae crops cultivated under hydroponic conditions. In contrast to tumorigenic agrobacteria, only a few genome sequences of rhizogenic agrobacteria are currently available. Here, we report the draft genome sequences of 27 rhizogenic Agrobacterium strains.

Isolation, characterization and genome analysis of an orphan phage FoX4 of the new Foxquatrovirus genus.

The growing interest in the therapeutic application of bacteriophages leads to a drastic increase in the number of sequenced genomes. Luckily, recent insights in phage taxonomy facilitate the classification of phages in a comprehensive and data-driven manner as recently proposed by the International Committee on Taxonomy of Viruses. In this research, we present the taxonomical classification of a novel, narrow host range Xanthomonas phage FoX4, isolated from a Brussels sprouts field in Belgium infested with Xanthomonas campestris pv. campestris. The phage has a limited ability to lyse a bacterial culture, yet adsorbs efficiently to its host. Based on its genome sequence and low similarity to previously described phages, the phage comprises the novel phage genus Foxquatrovirus.

The relation between visual orienting functions, daily visual behaviour and visuoperceptual performance in children with (suspected) cerebral visual impairment.

BACKGROUND: Children with cerebral visual impairment (CVI) present heterogeneous visual orienting functions (VOF) and higher-order perception. Multiple assessment methods evaluate CVI, but the relations between them remain unclear. AIM: To investigate the relations between VOF and (1) daily life behaviour and (2) visuoperceptual tests in children with (suspected) CVI. METHODS AND PROCEDURES: VOF were tested with a validated eye tracking-based paradigm. Visual perception was assessed using the children's visual impairment test for 3- to 6-year olds (CVIT 3-6) and (retrospective) visuoperceptual dimension results. Caregivers completed the Flemish cerebral visual impairment questionnaire (FCVIQ) and an expert panel scored relations between VOF and the other methods. We compared experts' survey responses with data-based results (linear mixed models and correlations). OUTCOMES AND RESULTS: Fourty-four children (23 boys, 21 girls; median age = 7y11mo, SD = 2y7mo) participated. Twenty-one experts completed the survey. Slower VOF was significantly associated with (1) object and face processing impairments, (2) visual (dis)interest, (3) worse visual spatial perception (to local motion and form stimuli), and (4) worse CVIT 3-6 object and scene recognition (to cartoon stimuli). CONCLUSIONS AND IMPLICATIONS: Integration of VOF with existing visual assessments provides a better clinical picture of CVI and can prevent misdiagnosing children as inattentive, incapable, or unmotivated.

Cobalt and silver nanocoatings for reactor dosimetry.

Activation foils are an important tool for the characterization of neutron fields. Some of the materials that are used in these foils have large interaction cross-sections that cause unwanted self-shielding effects. In practice experimenters minimize these effects by using aluminium alloys. An alternative approach can be a nanocoating of a pure material on a carrier. The validity of this approach is investigated in this work. Nanocoatings can be more flexible compared to alloys and can probably reduce the number of required post-irradiation gamma spectrometry measurements. Cobalt and silver nanocoatings were deposited by physical vapour deposition on nickel and aluminium carrier foils. The nanocoatings were tested in two irradiation campaigns in the Belgian Reactor 1 at SCK CEN. By depositing nanocoatings with different thickness and determining the corresponding number of activated atoms the inherent flexibility of the technique is demonstrated. When the dosimeters were punched from the carrier foils, the metal cylindrical punch damaged the nanocoatings which increased the spread on the number of atoms between different dosimeters. This is prevented by including a Ti interlayer of 5 nm between the carrier and the cobalt and silver layers. It was shown that this results in a coating with good homogeneity or minimal spread. This study shows that applying nanocoatings on a carrier is a valid technique to make dosimeters.

Bacteriophage therapy as a treatment strategy for orthopaedic-device-related infections: where do we stand?

Antibiotic resistance represents a key challenge of the 21st century. Since the pipeline of new antibiotics in development is limited, the introduction of alternative antimicrobial strategies is urgently required. Bacteriophage therapy, the use of bacterial viruses to selectively kill bacterial pathogens, is re-emerging as a potential strategy to tackle difficult-to-treat and multidrug-resistant pathogens. The last decade has seen a surge in scientific investigation into bacteriophage therapy, including targeting orthopaedic-device-related infections (ODRIs) in several successful case studies. However, pharmacological data, knowledge on the interplay with the immune system and, especially in ODRIs, the optimal local application strategy and treatment outcomes remain scarce. The present review reports the state-of-the-art in bacteriophage therapy in ODRIs and addresses the hurdles in establishing bacteriophage therapy under good clinical practice guidelines. These hurdles include a lack of data concerning bacteriophage production, processing, administration and dosing, as well as follow-up clinical monitoring reports. To overcome these challenges, an integrated clinical approach is required, supported by comprehensive legislature to enable expansive and correctly implemented clinical trials.

The effect of perceptual grouping on haptic numerosity perception.

We used a haptic enumeration task to investigate whether enumeration can be facilitated by perceptual grouping in the haptic modality. Eight participants were asked to count tangible dots as quickly and accurately as possible, while moving their finger pad over a tactile display. In Experiment 1, we manipulated the number and organization of the dots, while keeping the total exploration area constant. The dots were either evenly distributed on a horizontal line (baseline condition) or organized into groups based on either proximity (dots placed in closer proximity to each other) or configural cues (dots placed in a geometric configuration). In Experiment 2, we varied the distance between the subsets of dots. We hypothesized that when subsets of dots can be grouped together, the enumeration time will be shorter and accuracy will be higher than in the baseline condition. The results of both experiments showed faster enumeration for the configural condition than for the baseline condition, indicating that configural grouping also facilitates haptic enumeration. In Experiment 2, faster enumeration was also observed for the proximity condition than for the baseline condition. Thus, perceptual grouping speeds up haptic enumeration by both configural and proximity cues, suggesting that similar mechanisms underlie perceptual grouping in both visual and haptic enumeration.

The effects of aging on haptic 2D shape recognition.

We use the image-mediation model (Klatzky & Lederman, 1987) as a framework to investigate potential sources of adult age differences in the haptic recognition of two-dimensional (2D) shapes. This model states that the low-resolution, temporally sequential, haptic input is translated into a visual image, which is then reperceived through the visual processors, before it is matched against a long-term memory representation and named. In three experiments we tested groups of 12 older (mean age 73.11) and three groups of 12 young adults (mean age 22.80) each. In Experiment 1 we confirm age-related differences in haptic 2D shape recognition, and we show the typical age × complexity interaction. In Experiment 2 we show that if we facilitate the visual translation process, age differences become smaller, but only with simple shapes and not with the more complex everyday objects. In Experiment 3 we target the last step in the model (matching and naming) for complex stimuli. We found that age differences in exploration time were considerably reduced when this component process was facilitated by providing a category name. We conclude that the image-mediation model can explain adult-age differences in haptic recognition, particularly if the role of working memory in forming the transient visual image is considered. Our findings suggest that sensorimotor skills thought to rely on peripheral processes for the most part are critically constrained by age-related changes in central processing capacity in later adulthood.

The BOLD correlates of the visual P1 and N1 in single-trial analysis of simultaneous EEG-fMRI recordings during a spatial detection task.

Simultaneous EEG-fMRI measurements can combine the high spatial resolution of fMRI with the high temporal resolution of EEG. Therefore, we applied this approach to the study of peripheral vision. More specifically, we presented visual field quadrant fragments of checkerboards and a full central checkerboard in a simple detection task. A technique called "integration-by-prediction" was used to integrate EEG and fMRI data. In particular, we used vectors of single-trial ERP amplitude differences between left and right occipital electrodes as regressors in an ERP-informed fMRI analysis. The amplitude differences for the regressors were measured at the latencies of the visual P1 and N1 components. Our results indicated that the traditional event-related fMRI analysis revealed mostly activations in the vicinity of the primary visual cortex and in the ventral visual stream, while both P1 and N1 regressors revealed activation of areas in the temporo-parietal junction. We conclude that simultaneous EEG-fMRI in a spatial detection task can separate visual processing at 100-200 ms from stimulus onset from the rest of the information processing in the brain.

A case series of embryonal rhabdomyosarcoma of the head and neck in adults.

Embryonal rhabdomyosarcoma (RMS) is a rare malignant mesenchymal tumour that is believed to arise from cells committed to a skeletal muscle lineage. The head and neck region is among the most frequent locations for embryonal RMS in adults. We present a retrospective review of seven patients treated in our institution between 2000 and 2008. The age at diagnosis ranged from 19 to 41 years. One patient received primary surgery followed by adjuvant radiotherapy. Six inoperable patients were treated along a single chemotherapy protocol: the VIA-VIP regimen (a combination of vincristine, ifosfamide and doxorubicin (VIA) in alternation with etoposide, ifosfamide and cisplatin (VIP) administered in 3-weekly cycles), followed by local therapy, involving radiation therapy and/or surgery. An objective response to chemotherapy was observed in all six patients. Three out of seven patients remain disease-free with a median follow up of 4.5 years. Although the prognosis of head and neck embryonal RMS is worse in adults than in children, a multimodality treatment combining surgery, radiotherapy and intensive chemotherapy is feasible and effective in this population.

Shared neural resources between left and right interlimb coordination skills: the neural substrate of abstract motor representations.

Functional magnetic resonance imaging was used to reveal the shared neural resources between movements performed with effectors of the left versus right body side. Prior to scanning, subjects extensively practiced a complex coordination pattern involving cyclical motions of the ipsilateral hand and foot according to a 90 degrees out-of-phase coordination mode. Brain activity associated with this (nonpreferred) coordination pattern was contrasted with pre-existing isodirectional (preferred) coordination to extract the learning-related brain networks. To identify the principal candidates for effector-independent movement encoding, the conjunction of training-related activity for left and right limb coordination was determined. A dominantly left-lateralized parietal-to-(pre)motor activation network was identified, with activation in inferior and superior parietal cortex extending into intraparietal sulcus and activation in the premotor areas, including inferior frontal gyrus (pars opercularis). Similar areas were previously identified during observation of complex coordination skills by expert performers. These parietal-premotor areas are principal candidates for abstract (effector-independent) movement encoding, promoting motor equivalence, and they form the highest level in the action representation hierarchy.

Image descriptions in early and mid-level vision: what kind of model is this and what kind of models do we really need?

In The utility of image descriptions in the initial stages of vision: A case study of printed text, Watt and Dakin (2010) describe a model that integrates mechanisms at both early and middle stages of visual processing, and provide a demonstration of the application of the model to the relational organization of printed text. In the following, we discuss a number of the merits of this approach, but argue that it is (at this stage) highly difficult to assess the utility of this model as a plausible description of human visual processing. First, we indicate that the authors' description of the model is underspecified. Second, we question the generalizability of the model. Third, we argue that the model needs to be directly compared to quantitative empirical data. Fourth, we argue that the model needs to be directly compared to alternative models.

Effects of perceptual learning in visual backward masking on the responses of macaque inferior temporal neurons.

Learning is critical for fast and efficient object recognition in primates. To understand the neuronal correlates of behavioral improvements due to training, we recorded the responses of single neurons in the inferior temporal (IT) cortex of monkeys that were trained to recognize briefly presented, backward-masked objects. First we investigated training effects that are specific to the objects shown during training and that do not transfer to untrained objects. Only one of two monkeys tested showed object-specific training effects at the behavioral level, and only this monkey showed a transient object-specific increase in object selectivity for trained compared with untrained backward-masked objects. However, in each monkey a substantial part of the training effect transferred to untrained objects. To investigate the neural correlates of these object-independent training effects, we compared the neural responses to masked objects in trained monkeys to the responses in untrained monkeys. Training was associated with a reduction of the responses to the irrelevant masking patterns. These findings suggest that extensive training in recognizing backward-masked objects results in neural changes that reduce IT responses to the interfering irrelevant masking patterns and enhance the processing of the relevant objects.

Multiple routes to object matching from different viewpoints: mental rotation versus invariant features.

Previous research has shown that object recognition from different viewpoints often yields strong effects of viewpoint. However, for some objects and experimental paradigms almost complete viewpoint invariance is obtained. This suggests the existence of multiple routes to object recognition. In this study we further strengthen this notion by designing two different conditions using the same experimental paradigm (simultaneous matching) and highly similar objects (multiblock figures). In the first condition (involving a handedness violation), strong effects of viewpoint were obtained. In the second condition (involving an invariance violation), the effects of viewpoint were negligible. This result illustrates that asking under what circumstances object recognition is viewpoint dependent or independent is more fruitful than attempting to show that object recognition is either viewpoint dependent or independent.

Inferotemporal neurons represent low-dimensional configurations of parameterized shapes.

Behavioral studies with parameterized shapes have shown that the similarities among these complex stimuli can be represented using a low number of dimensions. Using psychophysical measurements and single-cell recordings in macaque inferotemporal (IT) cortex, we found an agreement between low-dimensional parametric configurations of shapes and the representation of shape similarity at the behavioral and neuronal level. The shape configurations, computed from both the perceived and neuron-based similarities, revealed a low number of dimensions and contained the same stimulus order as the parametric configurations. However, at a metric level, the behavioral and neural representations deviated consistently from the parametric configurations. These findings suggest an ordinally faithful but metrically biased representation of shape similarity in IT.

Matching multicomponent objects from different viewpoints: mental rotation as normalization?

Novel multicomponent objects were created, and 3 distractors were created for each object by changing the relations between the parts of the object. In a set of 5 experiments, target objects were presented as a motion sequence of multiple views or as a single view. Participants were asked to determine whether an image of an object, viewed from another viewpoint, was the same as the target object. The axis of rotation was aligned with one of the environmental axes or with the main axis of the object. The effects of viewpoint on performance imply that the matching of objects is viewpoint dependent and requires a process of normalization to undo the differences between the perceptual description and the stored object descriptions. The lack of a systematic effect of the axis of rotation, however, suggests that this normalization is best understood as not involving a 3-D transformation of stored 3-D object models.

Different effects of lorazepam and diazepam on perceptual integration.

Recent research has established the detrimental effect of lorazepam, a benzodiazepine, on both implicit and explicit memory. Furthermore, lorazepam is known to affect perceptual integration. Diazepam, on the other hand, though being a benzodiazepine too, only impairs explicit memory, leaving implicit memory fairly intact. Little is known about the effect of diazepam on perceptual integration. The present study aimed at filling in this gap, by comparing the effects of lorazepam and diazepam on the detection of discontinuities in random-shaped outlines. In line with previous findings, the results in a lorazepam-treated group were quite different from the results in a placebo-treated group. The results in a diazepam-treated group were analogous to the results in the placebo-treated group and different from the results in the lorazepam-treated group. This shows that lorazepam and diazepam differ, not only with respect to their effect on implicit memory, but also with respect to their effect on perceptual integration. It is argued that this bears important consequences for memory research that makes use of a pharmacological dissociation rationale.

Can neuroimaging really tell us what the human brain is doing? The relevance of indirect measures of population activity.

Neuroimaging studies using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) give an indication towards the localization of mental representations and processes in the human brain. It is not clear to what extent such global measures of neuronal activity, pooling across large populations of neurons, can reveal how certain computations are implemented by the neurons in such population ('computational neuroimaging'). Population activity is related tightly to single-cell activity when all neurons in the population have similar response properties. We describe some evidence from single-cell recordings in monkeys that indicates that neurons with similar response properties are not scattered randomly throughout the visual cortex. Notwithstanding this clustering, populations of nearby neurons are still rather heterogeneous, requiring some prudence in deriving single-cell response properties from population activity. The following review of recent neuroimaging studies of the visual system describes to what degree inferences about computations and representations can be drawn from these studies.