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Searching for generic behaviors has been one of the driving forces leading to a deep understanding and classification of diverse phenomena. Usually a starting point is the development of a phenomenology based on observations. Such is the case for power law distributions encountered in a wealth of situations coming from physics, geophysics, biology, lexicography as well as social and financial networks. This finding is however restricted to a range of values outside of which finite size corrections are often invoked. Here we uncover a universal behavior of the way in which elements of a system are distributed according to their rank with respect to a given property, valid for the full range of values, regardless of whether or not a power law has previously been suggested. We propose a two parameter functional form for these rank-ordered distributions that gives excellent fits to an impressive amount of very diverse phenomena, coming from the arts, social and natural sciences. It is a discrete version of a generalized beta distribution, given by f(r) = A(N+1-r)(b)/r(a), where r is the rank, N its maximum value, A the normalization constant and (a, b) two fitting exponents. Prompted by our genetic sequence observations we present a growth probabilistic model incorporating mutation-duplication features that generates data complying with this distribution. The competition between permanence and change appears to be a relevant, though not necessary feature. Additionally, our observations mainly of social phenomena suggest that a multifactorial quality resulting from the convergence of several heterogeneous underlying processes is an important feature. We also explore the significance of the distribution parameters and their classifying potential. The ubiquity of our findings suggests that there must be a fundamental underlying explanation, most probably of a statistical nature, such as an appropriate central limit theorem formulation.

Background. Antimicrobial resistance (AMR) poses a significant global health threat, necessitating a deeper understanding of bacterial adaptation mechanisms. Introduction. This study investigates the genotypic and phenotypic evolutionary trajectories of Escherichia coli under meropenem and gentamicin selection, and it benchmarks these findings against florfenicol-evolved strains. Methodology. Utilizing a downsized, three-layer acrylic modified “Microbial Evolution and Growth Arena (MEGA-plate) system”—scaled to 40 × 50 cm for sterile handling and uniform 37 °C incubation—we tracked adaptation over 9–13 days, enabling real-time visualization of movement across antibiotic gradients. Results. Meropenem exposure elicited pronounced genetic heterogeneity and morphological remodeling (filamentous and circular forms), characteristic of SOS-mediated division arrest and DNA-damage response. In contrast, gentamicin exposure produced a uniform resistance gene profile and minimal shape changes, suggesting reliance on conserved defenses without major morphological adaptation. Comprehensive genomic analysis revealed a core resistome of 22 chromosomal loci shared across all three antibiotics, highlighting potential cross-resistance and the central roles of baeR, gadX, and marA in coordinating adaptive responses. Gene ontology enrichment underscored the positive regulation of gene expression and intracellular signaling as key themes in resistance evolution. Discussion. Our findings illustrate the multifaceted strategies E. coli employs—combining metabolic flexibility with sophisticated regulatory networks—to withstand diverse antibiotic pressures. This study underscores the utility of the MEGA-plate system in dissecting spatiotemporal AMR dynamics in a controlled yet ecologically relevant context. Conclusions. The divergent responses to meropenem and gentamicin highlight the complexity of resistance development and reinforce the need for integrated, One Health strategies. Targeting shared regulatory hubs may open new avenues for antimicrobial intervention and help preserve the efficacy of existing drugs.

Human intracranial amygdala recordings reveal fast-latency responses to broad and low, but not high, spatial frequency components of fearful, but not happy or neutral, faces, which are not observed with unpleasant scenes. Amygdala fearful face responses are faster than in fusiform cortex, supporting a phylogenetically old, subcortical pathway to human amygdala. A fast, subcortical pathway to the amygdala is thought to have evolved to enable rapid detection of threat. This pathway's existence is fundamental for understanding nonconscious emotional responses, but has been challenged as a result of a lack of evidence for short-latency fear-related responses in primate amygdala, including humans. We recorded human intracranial electrophysiological data and found fast amygdala responses, beginning 74-ms post-stimulus onset, to fearful, but not neutral or happy, facial expressions. These responses had considerably shorter latency than fear responses that we observed in visual cortex. Notably, fast amygdala responses were limited to low spatial frequency components of fearful faces, as predicted by magnocellular inputs to amygdala. Furthermore, fast amygdala responses were not evoked by photographs of arousing scenes, which is indicative of selective early reactivity to socially relevant visual information conveyed by fearful faces. These data therefore support the existence of a phylogenetically old subcortical pathway providing fast, but coarse, threat-related signals to human amygdala.

As with many other trophic interactions, the interchange of microorganisms between plants and their herbivorous insects is unavoidable. To test the hypothesis that the composition and diversity of the insect bacteriome are driven by the bacteriome of the plant, the bacteriomes of both the plant Datura inoxia and its specialist insect Lema daturaphila were characterised using 16S sRNA gene amplicon sequencing. Specifically, the bacteriomes associated with seeds, leaves, eggs, guts, and frass were described and compared. Then, the functions of the most abundant bacterial lineages found in the samples were inferred. Finally, the patterns of co-abundance among both bacteriomes were determined following a multilayer network approach. In accordance with our hypothesis, most genera were shared between plants and insects, but their abundances differed significantly within the samples collected. In the insect tissues, the most abundant genera were Pseudomonas (24.64%) in the eggs, Serratia (88.46%) in the gut, and Pseudomonas (36.27%) in the frass. In contrast, the most abundant ones in the plant were Serratia (40%) in seeds, Serratia (67%) in foliar endophytes, and Hymenobacter (12.85%) in foliar epiphytes. Indeed, PERMANOVA analysis showed that the composition of the bacteriomes was clustered by sample type (F = 9.36, p < 0.001). Functional inferences relevant to the interaction showed that in the plant samples, the category of Biosynthesis of secondary metabolites was significantly abundant (1.4%). In turn, the category of Xenobiotics degradation and metabolism was significantly present (2.5%) in the insect samples. Finally, the phyla Proteobacteria and Actinobacteriota showed a pattern of co-abundance in the insect but not in the plant, suggesting that the co-abundance and not the presence–absence patterns might be more important when studying ecological interactions.

Cavernous sinus meningiomas (CSMs) remain a surgical challenge due to the intimate involvement of their contained nerves and blood vessels. Stereotactic radiosurgery (SRS) is a safe and effective minimally invasive alternative for the treatment of small- to medium-sized CSMs. Objective: To assess the medium- to long-term outcomes of SRS for CSMs with respect to tumour growth, prevention of further neurological deterioration and improvement of existing neurological deficits. This multicentric study included data from 15 European institutions. We performed a retrospective observational analysis of 1222 consecutive patients harbouring 1272 benign CSMs. All were treated with Gamma Knife stereotactic radiosurgery (SRS). Clinical and imaging data were retrieved from each centre and entered into a common database. All tumours with imaging follow-up of less than 24 months were excluded. Detailed results from 945 meningiomas (86%) were then analysed. Clinical neurological outcomes were available for 1042 patients (85%). Median imaging follow-up was 67 months (mean 73.4, range 24–233). Median tumour volume was 6.2 cc (+/−7), and the median marginal dose was 14 Gy (+/−3). The post-treatment tumour volume decreased in 549 (58.1%), remained stable in 336 (35.6%) and increased in only 60 lesions (6.3%), yielding a local tumour control rate of 93.7%. Only 27 (2.8%) of the 60 enlarging tumours required further treatment. Five- and ten-year actuarial progression-free survival (PFS) rates were 96.7% and 90.1%, respectively. Tumour control rates were higher for women than men (p = 0.0031), and also for solitary sporadic meningiomas (p = 0.0201). There was no statistically significant difference in outcome for imaging-defined meningiomas when compared with histologically proven WHO Grade-I meningiomas (p = 0.1212). Median clinical follow up was 61 months (mean 64, range 6–233). Permanent morbidity occurred in 5.9% of cases at last follow-up. Stereotactic radiosurgery is a safe and effective method for treating benign CSM in the medium term to long term.

Advances across the chemical and biological (life) sciences are increasingly enabled by ideas and tools from sectors outside these disciplines, with information and communication technologies playing a key role across 21 century scientific development. In the face of rapid technological change, the Organisation for the Prohibition of Chemical Weapons (OPCW), the implementing body of the Chemical Weapons Convention (“the Convention”), seeks technological opportunities to strengthen capabilities in the field of chemical disarmament. The OPCW Scientific Advisory Board (SAB) in its review of developments in science and technology examined the potential uses of emerging technologies for the implementation of the Convention at a workshop entitled “Innovative Technologies for Chemical Security”, held from 3 to 5 July 2017, in Rio de Janeiro, Brazil. The event, organized in cooperation with the International Union of Pure and Applied Chemistry (IUPAC), the National Academies of Science, Engineering and Medicine of the United States of America, the Brazilian Academy of Sciences, and the Brazilian Chemical Society, was attended by 45 scientists and engineers from 22 countries. Their insights into the use of innovative technological tools and how they might benefit chemical disarmament and non-proliferation informed the SAB’s report on developments in science and technology for the Fourth Review Conference of the Convention (to be held in November 2018), and are described herein, as are recommendations that the SAB submitted to the OPCW Director-General and the States Parties of the Convention. It is concluded that technologies exist or are under development that could be used for investigations, contingency, assistance and protection, reducing risks to inspectors, and enhancing sampling and analysis.

A major concern of patients who have stereotactic radiosurgery is the long-term risk of having a secondary intracranial malignancy or, in the case of patients with benign tumours treated with the technique, the risk of malignant transformation. The incidence of stereotactic radiosurgery-associated intracranial malignancy remains unknown; therefore, our aim was to estimate it in a population-based study to assess the long-term safety of this technique. We did a population-based, multicentre, cohort study at five international radiosurgery centres (Na Homolce Hospital, Prague, Czech Republic [n=2655 patients]; Ruber International Hospital, Madrid, Spain [n=1080], University of Pittsburgh Medical Center, Pittsburgh, PA, USA [n=1027]; University of Virginia, Charlottesville, VA, USA [n=80]; and NYU Langone Health System, New York, NY, USA [n=63]). Eligible patients were of any age, and had Gamma Knife radiosurgery for arteriovenous malformation, trigeminal neuralgia, or benign intracranial tumours, which included vestibular or other benign schwannomas, WHO grade 1 meningiomas, pituitary adenomas, and haemangioblastoma. Patients were excluded if they had previously had radiotherapy or did not have a minimum follow-up time of 5 years. The primary objective of the study was to estimate the incidence of stereotactic radiosurgery-associated intracranial malignancy, including malignant transformation of a benign lesion or development of radiation-associated secondary intracranial cancer, defined as within the 2 Gy isodose line. Estimates of age-adjusted incidence of primary CNS malignancies in the USA and European countries were retrieved from the Central Brain Tumor Registry of the United States (CBTRUS) and the International Agency for Research on Cancer (IARC) Global Cancer statistics. Of 14 168 patients who had Gamma Knife stereotactic radiosurgery between Aug 14, 1987, and Dec 31, 2011, in the five contributing centres, 4905 patients were eligible for the analysis (had a minimum follow-up of 5 years and no history of previous radiation therapy). Diagnostic entities included vestibular schwannomas (1011 [20·6%] of 4905 patients), meningiomas (1490 [30·4%]), arteriovenous malformations (1089 [22·2%]), trigeminal neuralgia (565 [11·5%]), pituitary adenomas (641 [13·1%]), haemangioblastoma (29 [0·6%]), and other schwannomas (80 [1·6%]). With a median follow-up of 8·1 years (IQR 6·0–10·6), two (0·06%) of 3251 patients with benign tumours were diagnosed with suspected malignant transformation and one (0·02%) of 4905 patients was considered a case of radiosurgery-associated intracranial malignancy, resulting in an incidence of 6·87 per 100 000 patient-years (95% CI 1·15–22·71) for malignant transformation and 2·26 per 100 000 patient-years (0·11–11·17) for radiosurgery-associated intracranial malignancy. Two (0·04%) of 4905 patients developed intracranial malignancies, which were judged unrelated to the radiation field. Overall incidence of radiosurgery-associated malignancy was 6·80 per 100 000 patients-years (95% CI 1·73–18·50), or a cumulative incidence of 0·045% (95% CI 0·00–0·34) over 10 years. The overall incidence of 6·8 per 100 000, which includes institutions from Europe and the USA, after stereotactic radiosurgery was found to be similar to the risk of developing a malignant CNS tumour in the general population of the USA and some European countries as estimated by the CBTRUS and IARC data, respectively. These data show that the estimated risk of an intracranial secondary malignancy or malignant transformation of a benign tumour in patients treated with stereotactic radiosurgery remains low at long-term follow-up, and is similar to the risk of the general population to have a primary CNS tumour. Although prospective cohort studies with longer follow-up are warranted to support the results of this study, the available evidence suggests the long-term safety of stereotactic radiosurgery and could support physicians counselling patients on Gamma Knife stereotactic radiosurgery. None.

ContextCushing disease (CD) due to adrenocorticotropic hormone–secreting pituitary tumors can be a management challenge.ObjectiveTo better understand the outcomes of stereotactic radiosurgery (SRS) for CD and define its role in management.DesignInternational, multicenter, retrospective cohort analysis.SettingTen medical centers participating in the International Gamma Knife Research Foundation.PatientsPatients with CD with >6 months endocrine follow-up.InterventionSRS using Gamma Knife radiosurgery.Main Outcome MeasuresThe primary outcome was control of hypercortisolism (defined as normalization of free urinary cortisol). Radiologic response and adverse radiation effects (AREs) were recorded.ResultsIn total, 278 patients met inclusion criteria, with a mean follow-up of 5.6 years (0.5 to 20.5 years). Twenty-two patients received SRS as a primary treatment of CD. Mean margin dose was 23.7 Gy. Cumulative initial control of hypercortisolism was 80% at 10 years. Mean time to cortisol normalization was 14.5 months. Recurrences occurred in 18% with initial cortisol normalization. Overall, the rate of durable control of hypercortisolism was 64% at 10 years and 68% among patients who received SRS as a primary treatment. AREs included hypopituitarism (25%) and cranial neuropathy (3%). Visual deficits were related to treatment of tumor within the suprasellar cistern (P = 0.01), whereas both visual (P < 0.0001) and nonvisual cranial neuropathy (P = 0.02) were related to prior pituitary irradiation.ConclusionsSRS for CD is well tolerated and frequently results in control of hypercortisolism. However, recurrences can occur. SRS should be considered for patients with persistent hypercortisolism after pituitary surgery and as a primary treatment in those unfit for surgery. Long-term endocrine follow-up is essential after SRS.We studied the outcomes of stereotactic radiosurgery for Cushing disease in 278 patients and found that this treatment can result in durable endocrine remission in appropriately selected patients.

ABSTRACT BACKGROUND Obsessive compulsive disorder (OCD) across its full spectrum of severity is a psychiatric illness affecting ∼2% to 3% of the general population and results in significant functional impairment. There are few large patient series regarding Gamma ventral capsulotomy (GVC). OBJECTIVE To evaluate clinical outcomes of severe medically refractory OCD treated with GVC. METHODS This is an international, multicenter, retrospective cohort study. Forty patients with pre-GVC Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores ≥ 24 (indicating severe OCD) were included. GVC was performed with 1 or 2 isocenters with a median maximum dose of 135 Gy (range, 120-180 Gy). Patients were deemed “responders” to GVC if there was ≥35% reduction of follow-up Y-BOCS scores, and considered in remission if their Y-BOCS scores were ≤16. The median follow-up was 36 mo (range, 6-96 mo). RESULTS The median pre-SRS Y-BOCS score was 35 (range, 24-40). Eighteen patients (45%) were considered “responders,” and 16 (40%) of them were in remission at their last follow-up. Nineteen patients (47.5%) remained stable with Y-BOCS of 33 (range, 26-36) following GVC, whereas 3 patients (7.5%) experienced worsening in Y-BOCS scores. Patients treated with 2 isocenters were more likely to have improvement in Y-BOCS score at 3 and 5 yr (P < .0005). Ten patients (25%) experienced post-GVC mood disturbance and neurological complications in 3 patients (7.5%). One patient developed radiation necrosis with edema that improved with steroids. CONCLUSION GVC serves as a reasonable treatment strategy for severe medical refractory OCD. Patients treated with 2 isocenters were more likely to have substantial improvement in OCD.

BackgroundPsychiatric neurosurgery is experiencing a revival. Beside deep brain stimulation (DBS), several ablative neurosurgical procedures are currently in use. Each approach has a different profile of advantages and disadvantages. However, many psychiatrists, ethicists, and laypeople are sceptical about psychiatric neurosurgery.MethodsWe identify the main concerns against psychiatric neurosurgery, and discuss the extent to which they are justified and how they might be overcome. We review the evidence for the effectiveness, efficacy and safety of each approach, and discuss how this could be improved. We analyse whether and, if so, how randomised controlled trials (RCTs) can be used in the different approaches, and what alternatives are available if conducting RCTs is impossible for practical or ethical reasons. Specifically, we analyse the problem of failed RCTs after promising open-label studies.ResultsThe main concerns are: (i) reservations based on historical psychosurgery, (ii) concerns about personality changes, (iii) concerns regarding localised interventions, and (iv) scepticism due to the lack of scientific evidence. Given the need for effective therapies for treatment-refractory psychiatric disorders and preliminary evidence for the effectiveness of psychiatric neurosurgery, further research is warranted and necessary. Since psychiatric neurosurgery has the potential to modify personality traits, it should be held to the highest ethical and scientific standards.ConclusionsPsychiatric neurosurgery procedures with preliminary evidence for efficacy and an acceptable risk–benefit profile include DBS and micro- or radiosurgical anterior capsulotomy for intractable obsessive–compulsive disorder. These methods may be considered for individual treatment attempts, but multi-centre RCTs are necessary to provide reliable evidence.