Chondromyxoid fibroma management: a single institution experience of 22 cases

Background: Several different strategies have been reported for the treatment of chondromyxoid fibromas, all with variable outcomes and high recurrence rates. Methods: We report on 22 consecutive cases of chondromyxoid fibromas treated by intralesional curettage, four of which had adjuvant cementation at our institution between 2003 and 2010. We assessed the functional outcome using the Musculoskeletal Tumour Society (MSTS) scoring system. Results: Nine males and 16 females with a mean age of 36.5 years (range 11 to 73) and a mean follow-up of 60.7 months were included in the study. Local recurrence occurred in two patients (9%) within the first 2 years following the index procedure. This was treated by re-curettage only of the residual defect. Two postoperative complications occurred: a superficial wound infection in one patient and a transient deep peroneal nerve neurapraxia in the other. The mean postoperative MSTS score was 96.7%. Conclusions: Intralesional curettage and cementation is as an effective treatment strategy for chondromyxoid fibromas, providing satisfactory functional results with a low recurrence rate. Careful case selection with stringent clinical and radiographic follow-up is recommended

Monotonicity of Fitness Landscapes and Mutation Rate Control

A common view in evolutionary biology is that mutation rates are minimised. However, studies in combinatorial optimisation and search have shown a clear advantage of using variable mutation rates as a control parameter to optimise the performance of evolutionary algorithms. Much biological theory in this area is based on Ronald Fisher's work, who used Euclidean geometry to study the relation between mutation size and expected fitness of the offspring in infinite phenotypic spaces. Here we reconsider this theory based on the alternative geometry of discrete and finite spaces of DNA sequences. First, we consider the geometric case of fitness being isomorphic to distance from an optimum, and show how problems of optimal mutation rate control can be solved exactly or approximately depending on additional constraints of the problem. Then we consider the general case of fitness communicating only partial information about the distance. We define weak monotonicity of fitness landscapes and prove that this property holds in all landscapes that are continuous and open at the optimum. This theoretical result motivates our hypothesis that optimal mutation rate functions in such landscapes will increase when fitness decreases in some neighbourhood of an optimum, resembling the control functions derived in the geometric case. We test this hypothesis experimentally by analysing approximately optimal mutation rate control functions in 115 complete landscapes of binding scores between DNA sequences and transcription factors. Our findings support the hypothesis and find that the increase of mutation rate is more rapid in landscapes that are less monotonic (more rugged). We discuss the relevance of these findings to living organisms

Delays in the diagnosis and treatment of bone and joint tuberculosis in the United Kingdom

AIMS: Tuberculosis (TB) infection of bones and joints accounts for 6.7% of TB cases in England, and is associated with significant morbidity and disability. Public Health England reports that patients with TB experience delays in diagnosis and treatment. Our aims were to determine the demographics, presentation and investigation of patients with a TB infection of bones and joints, to help doctors assessing potential cases and to identify avoidable delays. PATIENTS AND METHODS: This was a retrospective observational study of all adults with positive TB cultures on specimens taken at a tertiary orthopaedic centre between June 2012 and May 2014. A laboratory information system search identified the patients. The demographics, clinical presentation, radiology, histopathology and key clinical dates were obtained from medical records. RESULTS: A total of 31 adult patients were identified. Their median age was 37 years (interquartile range (IQR): 29 to 53); 21 (68%) were male; 89% were migrants. The main sites affected were joints (10, 32%), the spine (8, 26%) and long bones (6, 19%); 8 (26%) had multifocal disease. The most common presenting symptoms were pain (29/31, 94%) and swelling (26/28, 93%). 'Typical' symptoms of TB, such as fever, sweats and weight loss, were uncommon. Patients waited a median of seven months (IQR 3 to 13.5) between the onset of symptoms and referral to the tertiary centre and 2.3 months (IQR 1.6 to 3.4.)) between referral and starting treatment. Radiology suggested TB in 26 (84%), but in seven patients (23%) the initial biopsy specimens were not sent for mycobacterial culture, necessitating a second biopsy. Rapid Polymerase Chain Reaction-based testing for TB using Xpert MTB/RIF was performed in five patients; 4 (80%) tested positive for TB. These patients had a reduced time between the diagnostic biopsy and starting treatment than those whose samples were not tested (median eight days versus 36 days, p = 0.016). CONCLUSION: Patients with bone and joint TB experience delays in diagnosis and treatment, some of which are avoidable. Maintaining a high index of clinical suspicion and sending specimens for mycobacterial culture are crucial to avoid missing cases. Rapid diagnostic tests reduce delays and should be performed on patients with radiological features of TB. Cite this article: Bone Joint J 2018;100-B:119-24

Orexinergic Input to Dopaminergic Neurons of the Human Ventral Tegmental Area

The mesolimbic reward pathway arising from dopaminergic (DA) neurons of the ventral tegmental area (VTA) has been strongly implicated in reward processing and drug abuse. In rodents, behaviors associated with this projection are profoundly influenced by an orexinergic input from the lateral hypothalamus to the VTA. Because the existence and significance of an analogous orexigenic regulatory mechanism acting in the human VTA have been elusive, here we addressed the possibility that orexinergic neurons provide direct input to DA neurons of the human VTA. Dual-label immunohistochemistry was used and orexinergic projections to the VTA and to DA neurons of the neighboring substantia nigra (SN) were analyzed comparatively in adult male humans and rats. Orexin B-immunoreactive (IR) axons apposed to tyrosine hydroxylase (TH)-IR DA and to non-DA neurons were scarce in the VTA and SN of both species. In the VTA, 15.062.8% of TH-IR perikarya in humans and 3.260.3% in rats received orexin B-IR afferent contacts. On average, 0.2460.05 and 0.0560.005 orexinergic appositions per TH-IR perikaryon were detected in humans and rats, respectively. The majority(86–88%) of randomly encountered orexinergic contacts targeted the dendritic compartment of DA neurons. Finally, DA neurons of the SN also received orexinergic innervation in both species. Based on the observation of five times heavierorexinergic input to TH-IR neurons of the human, compared with the rat, VTA, we propose that orexinergic mechanism acting in the VTA may play just as important roles in reward processing and drug abuse in humans, as already established well in rodents

Search for time-dependent B0s - B0s-bar oscillations using a vertex charge dipole technique

We report a search for B0s - B0s-bar oscillations using a sample of 400,000 hadronic Z0 decays collected by the SLD experiment. The analysis takes advantage of the electron beam polarization as well as information from the hemisphere opposite that of the reconstructed B decay to tag the B production flavor. The excellent resolution provided by the pixel CCD vertex detector is exploited to cleanly reconstruct both B and cascade D decay vertices, and tag the B decay flavor from the charge difference between them. We exclude the following values of the B0s - B0s-bar oscillation frequency: Delta m_s < 4.9 ps-1 and 7.9 < Delta m_s < 10.3 ps-1 at the 95% confidence level.Comment: 18 pages, 3 figures, replaced by version accepted for publication in Phys.Rev.D; results differ slightly from first versio

Performance deficits of NK1 receptor knockout mice in the 5 choice serial reaction time task: effects of d Amphetamine, stress and time of day.

Background The neurochemical status and hyperactivity of mice lacking functional substance P-preferring NK1 receptors (NK1R-/-) resemble abnormalities in Attention Deficit Hyperactivity Disorder (ADHD). Here we tested whether NK1R-/- mice express other core features of ADHD (impulsivity and inattentiveness) and, if so, whether they are diminished by d-amphetamine, as in ADHD. Prompted by evidence that circadian rhythms are disrupted in ADHD, we also compared the performance of mice that were trained and tested in the morning or afternoon. Methods and Results The 5-Choice Serial Reaction-Time Task (5-CSRTT) was used to evaluate the cognitive performance of NK1R-/- mice and their wildtypes. After training, animals were tested using a long (LITI) and a variable (VITI) inter-trial interval: these tests were carried out with, and without, d-amphetamine pretreatment (0.3 or 1 mg/kg i.p.). NK1R-/- mice expressed greater omissions (inattentiveness), perseveration and premature responses (impulsivity) in the 5-CSRTT. In NK1R-/- mice, perseveration in the LITI was increased by injection-stress but reduced by d-amphetamine. Omissions by NK1R-/- mice in the VITI were unaffected by d-amphetamine, but premature responses were exacerbated by this psychostimulant. Omissions in the VITI were higher, overall, in the morning than the afternoon but, in the LITI, premature responses of NK1R-/- mice were higher in the afternoon than the morning. Conclusion In addition to locomotor hyperactivity, NK1R-/- mice express inattentiveness, perseveration and impulsivity in the 5-CSRTT, thereby matching core criteria for a model of ADHD. Because d-amphetamine reduced perseveration in NK1R-/- mice, this action does not require functional NK1R. However, the lack of any improvement of omissions and premature responses in NK1R-/- mice given d-amphetamine suggests that beneficial effects of this psychostimulant in other rodent models, and ADHD patients, need functional NK1R. Finally, our results reveal experimental variables (stimulus parameters, stress and time of day) that could influence translational studies

Humans and Insects Decide in Similar Ways

Behavioral ecologists assume that animals use a motivational mechanism for decisions such as action selection and time allocation, allowing the maximization of their fitness. They consider both the proximate and ultimate causes of behavior in order to understand this type of decision-making in animals. Experimental psychologists and neuroeconomists also study how agents make decisions but they consider the proximate causes of the behavior. In the case of patch-leaving, motivation-based decision-making remains simple speculation. In contrast to other animals, human beings can assess and evaluate their own motivation by an introspection process. It is then possible to study the declared motivation of humans during decision-making and discuss the mechanism used as well as its evolutionary significance. In this study, we combine both the proximate and ultimate causes of behavior for a better understanding of the human decision-making process. We show for the first time ever that human subjects use a motivational mechanism similar to small insects such as parasitoids [1] and bumblebees [2] to decide when to leave a patch. This result is relevant for behavioral ecologists as it supports the biological realism of this mechanism. Humans seem to use a motivational mechanism of decision making known to be adaptive to a heterogeneously distributed resource. As hypothesized by Hutchinson et al. [3] and Wilke and Todd [4], our results are consistent with the evolutionary shaping of decision making because hominoids were hunters and gatherers on food patches for more than two million years. We discuss the plausibility of a neural basis for the motivation mechanism highlighted here, bridging the gap between behavioral ecology and neuroeconomy. Thus, both the motivational mechanism observed here and the neuroeconomy findings are most likely adaptations that were selected for during ancestral times

An Ancient Relation between Units of Length and Volume Based on a Sphere

The modern metric system defines units of volume based on the cube. We propose that the ancient Egyptian system of measuring capacity employed a similar concept, but used the sphere instead. When considered in ancient Egyptian units, the volume of a sphere, whose circumference is one royal cubit, equals half a hekat. Using the measurements of large sets of ancient containers as a database, the article demonstrates that this formula was characteristic of Egyptian and Egyptian-related pottery vessels but not of the ceramics of Mesopotamia, which had a different system of measuring length and volume units

Effects of DSP4 and methylphenidate on spatial memory performance in rats

In this experiment, we have investigated the spatial memory performance of rats following a central noradrenaline depletion induced by three different doses of the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) and following administration of three different doses of methylphenidate (MPH). The rats were required to find food pellets hidden on a holeboard. The sole administration of DSP4 induced only minor cognitive deficits. However, the treatment with MPH increased the reference memory error, the impulsivity and the motor activity of the DSP4-treated rats. Since the noradrenergic terminals in a DSP4-treated rat are significantly reduced, the administration of MPH has little effect on the noradrenergic system and increases dopaminergic rather than noradrenergic activity, resulting in an imbalance with relatively high dopaminergic and low noradrenergic activities. It is suggested that a reduction of noradrenaline and an increase of dopamine induce ADHD-related deficits and that the depletion of noradrenaline is not sufficient for an appropriate rat model of ADHD