In normal anatomy, the anterior tibial artery is typically the first branch of the popliteal artery before it becomes the tibioperoneal trunk. The normal course of the anterior tibial artery includes piercing through the interosseus membrane and continuing through the anterior compartment. It then continues onto the dorsum of the foot as the dorsalis pedis artery at the level of the malleoli. We describe a unique case of an anomalous origin of the dorsalis pedis artery from the peroneal artery. It is important for vascular surgeons to be aware of this variant while interpreting arteriograms of the lower extremity. It can be easily misinterpreted as an occluded distal anterior tibial artery with reconstitution of the dorsalis pedis artery from the collaterals. The leg, foot, and ankle receive arterial blood from the popliteal artery and its associated branches. A complete understanding of normal anatomy is crucial to the treatment of vascular disease. In the posterior region of the proximal tibiofibular joint, the popliteal artery gives off the anterior tibial artery and continues as the tibioperoneal trunk . The antDistally, the anterior tibial artery passes deep to the extensor retinaculum and continues onto the dorsum of the foot as the dorsalis pedis artery (DPA) at the level of the malleoli. This location also serves as an anatomical landmark for pulse palpation . The DPAIn addition to a robust understanding of normal lower extremity vascular anatomy, an awareness of the anatomic variants such as those described in this report, is necessary for application in vascular, orthopedic, and radiologic medicine. In this report, we describe an anomalous origin of the dorsalis pedis artery from the peroneal artery which holds important clinical implications including interpretation of arteriograms, estimation of disease burden in peripheral arterial disease, and revascularization planning.Cadaveric dissection of a 94-year-old male who died of end-stage cerebral infarction revealed a unilateral anomalous origin of the right dorsalis pedis artery. Examination of the lower extremity revealed no scars suggestive of prior operations. The right popliteal artery entered the posterior compartment of the leg from the popliteal fossa and gave rise to the right anterior tibial artery and the right tibioperoneal trunk. The path of the right anterior tibial artery was traced through the proximal oval aperture in the interosseous membrane to reach the anterior compartment of the leg Figure . The right tibioperoneal trunk provided the right posterior tibial artery medially and the right peroneal artery laterally. The right anterior tibial artery entered the anterior compartment of the leg and was identified intermediate to tibialis anterior muscle and extensor hallucis longus muscle running longitudinally with the right anterior tibial veins and the right deep peroneal nerve. The right anterior tibial artery became hypoplastic and terminated as muscular and fascial branches. The right peroneal artery descended in the posterior compartment of the leg deep to the transverse intermuscular septum. It was then visualized passing through the distal oval aperture in the interosseous membrane to enter the anterior compartment of the leg as the perforating branch of the peroneal artery. The right perforating branch of the peroneal artery bifurcated into a smaller medial branch and a larger lateral branch. The medial branch was seen anastomosing with the anterior tibial artery. This is where the anterior tibial artery becomes hypoplastic and terminates. The lateral branch passed deep to the tendons of fibularis tertius and extensor digitorum longus muscles to continue as the right DPA Figure . The right DPA continued distally alongside the right dorsalis pedis veins and the right deep peroneal nerve on the dorsum of the right foot.Anatomical variations of the DPAVariations have been identified in the origin, course, and branching pattern of the DPA. Anomalous origin of DPA from the perforating branch of the peroneal artery has been described before in both cadaveric and arteriogram studies. According to Hemamalini and Manjunatha, an anomalous origin of DPA can occur bilaterally or unilaterally . Three iVazquez et al. studied the blood supply of the foot and ankle using a sample of 150 human embalmed cadavers. It was noted that 287 cases (95.7%) displayed a normal continuation of the anterior tibial artery to DPA distal to the talocrural joint. In these cases, the DPA was identified lateral to the tendon of the extensor hallucis longus and medial to the tendons of the extensor digitorum longus. Six cases (2%) demonstrated a lateral deviation of the anterior tibial artery as far as the lateral malleolus. They reported an enlarged perforating branch of the peroneal artery continuing as DPA in four out of 300 limbs, for an incidence rate of 1.3%. Lastly, three cases (1%) demonstrated the origination of an additional lateral branch from the anterior tibial artery that replaced the perforating branch of the peroneal artery [This anomaly was additionally studied by Keen via cadaveric dissection of 140 subjects, or 280 limbs, and anomalous origin was discovered unilaterally 12 times, and bilaterally once, demonstrating 5% incidence . Kim et Clinical implicationsAwareness of anatomical variations in the origin, course, and branching patterns of DPA is important for vascular surgeons, orthopedic surgeons, and radiologists. Documentation of dorsalis pedis pulse via palpation or Doppler is useful in evaluating anterior compartment syndrome and peripheral arterial diseases (PAD) ,10. HoweEmbryonic originVariations in the branching pattern of foot and ankle vasculature can be attributed to disruption of normal embryonic development . The devEven though anomalous variations in lower extremity vascular anatomy have been described in the literature, they have been largely ignored within medical education. Vascular practitioners are often faced with recognition and treatment of anomalous vascular anatomy without adequate background education or understanding of the possible variants. This report describes a key variation of lower extremity vasculature by highlighting the peroneal origin of the DPA. Recognition of this variant has numerous clinical applications including radiologic interpretation of arteriogram studies, palpation, and bedside Doppler of pulses, and planning of revascularization efforts.


Psychiatry has changed a lot during the last decades and lot of effort has been made to ensure that treatment of schizophrenia spectrum disorders is in line with modern science of medicine. Therefore, in everyday practice the psychiatrist is in a constant process of decision making when to start pharmacological treatment of early psychosis and with what dosage. The lecture will include evidence-based treatment options, the aspects of clinical practice and the power of shared decision-making in psychiatry.None Declared


The nerve supply of the distal part of the hindlimb is very important for the motor and sensory function of the hindlimb. The dromedary camel is historically and currently a very important species for transportation, riding, and racing in many countries. Therefore, understanding the structural components of its limbs is highly important for clinical and surgical purposes. The nerve supply of the distal part of the hindlimb has been discussed in a few domestic species; however, little is known about the nerve supply in the dromedary camel. This study aimed to show the anatomical structure of the nerve supply of the distal part of the hindlimb. Dromedary hindlimbs were collected from a slaughterhouse. Then, they were fixed using 10% formalin. Subsequently, dissection was performed to show the group of nerves that supply the hindlimb’s distal portion. The result shows the branches of the superficial fibular nerve and tibial nerve. It is very important to understand the nerves that supply the distal part of the hindlimb for anesthesia of the skin, tendons and joints.This study aimed to describe the anatomy of the nerve supply of the hindlimb’s distal portion in a dromedary camel’s foot. In our study, we used ten adult slaughtered dromedary camels  of different sexes and ages (4–6 years). The hindlimbs were preserved using 10% formalin for about one week. The distal part of the hindlimb of the camels was dissected with extreme precision to show the group of nerves responsible for the nervous supply to the distal part of the hindlimb in dromedary camels. This study shows the numerous branches of the superficial fibular nerve along its extension to the dorsal surface metatarsus and the abaxial aspect of the third digit. The results show that the tibial nerve possesses many branches along its extension to the plantar surface skin of the metatarsus. Additionally, it provides the axial and abaxial plantar surfaces of the fourth digit and the interdigital surfaces as well as its branches to supply the plantar-abaxial and plantar-axial of the third digit. The present study shows the anatomical nerve supply of the hindlimb’s distal portion that is essential for anesthesia and surgery in this region. The origin and distribution of the sciatic and femoral nerves have been studied in bovines ,2, sheepKnowledge of the position and distribution of nerves in the distal parts of limbs is of great importance, especially for treating tendonitis, osteoarthritis and sesamoiditis in dogs . The objFor this work, we used twenty distal hindlimbs of ten freshly slaughtered adult dromedary camels of different sexes and ages (4–6 years). The specimens were obtained from a typical Buraydah slaughterhouse, Qassim Region, KSA. The hindlimb samples were fixed in 10% formalin solution for about one week. Then, samples were washed with distal water, and the skin was removed to be dissected. In order to remove the tissue around the nerves of the distal hindlimb, the nerves were gently massaged with gauze pieces bathed in 1% glacial acetic acid ,21. The The distal part of the hindlimb in camels receives its nerve supply from the terminal branches of the ischiatic nerve, including the common fibular or  and tibial nerves. Nn.dorsalis digitalis communis III and IV)     continues along the medial surface of the fourth IV digit  continues along the lateral surface of the third III digit  continues along the medial surface of the third III digit     )  to supply the axial and abaxial aspects of the III and IV digits     .Lateralis. b) of the lateral plantar nerve at the fetlock joint continues on the lateral aspect of the IV digit as an abaxial plantar proper digital nerve of the IV digit   supplies the plantar-abaxial aspect of the fourth digit’s skin  recorded that the superficial fibular nerve divides into the common dorsal nerves of the III and II digits . These fThe common dorsal digital IV nerve continues as the abaxial dorsal proper digital nerve of the IV digit. These results are consistent with the previously reported locations in camels ,25, in cThe common dorsal digital III nerve in our work has three branches, including the axial dorsal proper digital nerve of the IV digit, the axial dorsal proper digital nerve of the III digit, and the abaxial dorsal proper digital nerve of the III digit. These results disagree with what was reported  in camelThe dorsal aspect of the pes was dorsally innervated by the abaxial dorsal proper digital nerve of the IV digit from the common dorsal digital IV nerve and the axial and abaxial dorsal proper digital nerves of the III digit from the common dorsal digital III nerve of the superficial fibular nerve. The relevant findings disagree with ,23,24 inIn domestic animals, the foot structures’ sensitive innervation was investigated . It is mIn the dorsal section of the hindlimb, the superficial fibular nerve continues to be the dorsal common digital nerve. The dorsal common digital nerve splits into the dorsal proper digital nerves, which feed the axial and abaxial surfaces of the corresponding digits ,27,28,29The tibial nerve’s division into medial and lateral plantar nerves confirms the pattern described in goats , domestiThe current study revealed that the tibial nerve divided at the proximal third of the metatarsus into two branches, namely the lateral and medial plantar branches. This result is inconsistent in camels, as in other studies, the division of the tibia nerve was observed at the tarsus , while iThe medial plantar branch continues as a common plantar digital nerve of the III digit. Our findings disagree with those of other studies on camels, which reported that the medial plantar nerve continues as the common plantar digital nerve of the II digit .Our results confirm that the medial plantar branch continues as the abaxial plantar proper digital nerve of digit IV in domestic animals , in boviThe medial plantar branch divides into the axial plantar proper digital nerve of the III digit and the abaxial plantar proper digital nerve of the III digit. Similar findings were reported in previous studies in domestic animals ,13. In cSmuts et al. (1986) recorded that the medial plantar nerve divides into common plantar digital nerves of the II and III digits . In contIn this study, the lateral plantar nerve divides into the following two branches: the medial  branch and the lateral branch. The lateral branch continues as the abaxial plantar proper digital nerve IV of the digit and supplies the plantar-abaxial aspect of the IV digit. These findings are in agreement with the results of other studies in camels ,23,24, iOur results show the medial plantar digital nerve bifurcates from the tibial nerve at the tarsus level. They both continue together distally to the middle of the metatarsal bones. Then, they divide into the plantar common digital nerves II–IV. After that, they continue medially, becoming the plantar proper digital II abaxial nerve. Our results are similar to the findings reported in dogs ,31 and iThe saphenous nerve distribution on the cranial and medial surface of the camel leg was similar to that described in bovines , camels Finally, these results show that the nerve distribution of the distal parts of the hindlimbs are of great importance, because they will help in the determination of the regional anesthesia of the different nerves in the distal hindlimb, especially in the treatment of tendonitis, osteoarthritis and sesamoiditis ,36. On tThe findings show the anatomical structure of the nerve supply of the distal hindlimb in dromedary camels. We showed the nerve blocks and their distribution within this region, including the skin, tendons and joints. The findings will assist in successful anesthesia and surgery in this region.


Scramjet engines are considered a highly promising technology for improving high-speed flight. In this study, we investigate the effects of using multi-extruded nozzles on fuel mixing and distribution inside the combustion chamber at supersonic flow. Additionally, we explore the impact of an inner air jet on fuel mixing in annular nozzles. To model fuel penetration in the combustor, we employ a computational technique. Our study compares the roles of three different extruded injectors on fuel diffusion and distribution at supersonic cross-flow. Our findings reveal that the use of an inner air jet increases fuel mixing in the annular jet, while the use of extruded nozzles improves fuel distribution by enhancing the vortices between injectors. These results demonstrate the potential benefits of incorporating multi-extruded nozzles and inner air jets in the design of scramjet engines. One of the key challenges in designing these engines is achieving efficient fuel mixing and distribution at supersonic flow within the combustion chamber. In this context, the present study investigates the use of multi extruded nozzles to enhance fuel mixing and distribution. The study also explores the impact of an inner air jet on fuel mixing in annular nozzles. The computational modeling technique is employed to analyze the fuel penetration and diffusion in the combustor5. The study compares the performance of three different extruded injectors in terms of fuel diffusion and distribution at supersonic cross flow. The findings reveal that the use of extruded nozzles and inner air jet can significantly improve fuel mixing and distribution by enhancing the vortices between injectors. The results of this study have important implications for the design and development of more efficient and effective scramjet engines8.The development of scramjet engines has received considerable attention in recent years due to their potential to improve high-speed flight11. The critical challenge in designing these engines is to achieve efficient fuel mixing and distribution, as the combustion process is highly sensitive to these factors14. One way to improve fuel mixing and distribution is by using multi-nozzle injectors. A study15 investigated the use of multi-jet injectors in a Mach 6 scramjet combustor and found that the use of multi-jet injectors improved the combustion efficiency and reduced the flame length.Scramjet engines have been a topic of extensive research due to their potential to achieve high-speed flight and space access17 investigated the use of transverse injection in a Mach 4 scramjet engine and found that it significantly improved fuel mixing and distribution.Another approach to improve fuel mixing and distribution is by using transverse injection, where fuel is injected perpendicular to the air flow. Several studies21 investigated the use of swirling flow in a Mach 2.5 scramjet engine and found that it improved fuel mixing and distribution by promoting turbulence and increasing residence time. The impact of fuel injection pressure on fuel mixing and distribution has also been studied. Many papers26 investigated the effect of fuel injection pressure on the combustion efficiency of a Mach 3 scramjet engine and found that higher injection pressures improved fuel mixing and distribution, resulting in higher combustion efficiency.The use of swirling flow to enhance fuel mixing and distribution has also been explored. Many papers29 investigated the effect of nozzle geometry on the combustion efficiency of a Mach 5 scramjet engine and found that the use of lobed injectors improved fuel mixing and distribution compared to circular injectors.The impact of nozzle shape and geometry on fuel mixing and distribution has also been explored. Many papers33. These studies provide valuable insights for the design and development of more efficient and effective scramjet engines36.In summary, there have been various approaches to improving fuel mixing and distribution in scramjet engines, including the use of multi-nozzle injectors, transverse injection, swirling flow, higher injection pressures, and optimized nozzle geometryThis study has tried to investigate the influence of different arrangements of extruded lobe-injectors on the fuel penetration and shock interactions inside the combustion chamber. To do this, shock waves are compared on the jet planes to reveals the influence of extruded configurations on the fuel mixing mechanism at supersonic flow. Various lobe nozzles are investigated as demonstrated in Fig. 40. The shock wave formation is inherently happened in our model and consequently, the energy equation must be considered in our modeling42. Meanwhile, the turbulence effects are also important in our model and SST model of turbulence is considered for the calculation of viscosity43. The secondary gas of hydrogen is also modeled as fuel jet and mass transport equation is also used with Fick. Law for estimation of the diffusion of hydrogen gas45. Reactions are not considered in this study. The air flow is considered as ideal gas in the present model51.The simulation of high-speed air stream with compressibility effects is mainly done via solving RANS equations for continuum domain52. The usage of theoretical method is conventional in engineering applications56.Figure The produced grid for the selected computational domain is displayed in Fig. 38  down stream of three suggested nozzle configurations are done in Fig. Comparison of the circulation strength downstream of the proposed configurations is presented in Fig. Figure This study focuses on investigating the effects of multi extruded injectors on the fuel mixing mechanism in scramjet engines. Specifically, we examine the roles of three different types of nozzles located inside the engine's combustor, including annular and coaxial nozzles. To model the release of fuel jet from the extruded nozzles at supersonic cross flow, we develop a computational fluid dynamic approach. Through this approach, we compare the mixing efficiency and circulation power of each model. Our findings indicate that the use of coaxial jet nozzles decreases the circulation power, while achieving maximum fuel mixing efficiency. Additionally, we observe that the utilization of an inner air jet in the coaxial configuration further enhances fuel mixing in the nozzle gap.


One of the effective treatment options for intracranial aneurysms is stent-assisted coiling. Though, previous works have demonstrated that stent usage would result in the deformation of the local vasculature. The effect of simple stent on the blood hemodynamics is still uncertain. In this work, hemodynamic features of the blood stream on four different ICA aneurysm with/without interventional are investigated. To estimate the relative impacts of vessel deformation, four distinctive ICA aneurysm is simulated by the one-way FSI technique. Four hemodynamic factors of aneurysm blood velocity, wall pressure and WSS are compared in the peak systolic stage to disclose the impact of defamation by the stent in two conditions. The stent usage would decrease almost all of the mentioned parameters, except for OSI. Stenting reduces neck inflow rate, while the effect of interventional was not consistent among the aneurysms. The deformation of an aneurysm has a strong influence on the hemodynamics of an aneurysm. This outcome is ignored by most of the preceding investigations, which focused on the pre-interventional state for studying the relationship between hemodynamics and stents. Present results show that the application of stent without coiling would improve most hemodynamic factors, especially when the deformation of the aneurysm is high enough. The effects of hemodynamic forces on the wall of the intracranial artery may result in a pathological stretching of the vessel wall, and a deformed vessel is known as an Intracranial Aneurysm (IA). The development of IA is relevant to many pathophysiological factors, not only the hemodynamic ones, e.g., endothelial function, anatomic variations (certain areas in the Circle of Willis) are more vulnerable Liu . The maiThe primary hemodynamic factors of Oscillatory shear index (OSI), Wall shear stress (WSS) and Relative residence time (RRT) are introduced for the comparison of the different ICA aneurysms  and computed tomography angiography (CIA). In fact, these techniques enable researchers to access the main geometrical aspects of the aneurysm and use them for further investigations  is used to model of blood flow inside the aneurysm and calculating shear stress on the aneurysm wall. Comparisons of blood velocity and stream are also presented to reveal the influence of aneurysm deformation on the blood and its impact on the wall of the vessel.After evaluating of more than 30 ICA aneurysms, the geometries (.stl file) of four distinctive aneurysms are chosen from the Aneurisk website , this study reports WSS and average pressure on the vessel and mean velocity inside the sac for this stage. Meanwhile, the OSI value is calculated at the end of the third cardiac cycle (3000 steps) .As explained in the previous sections, the main attitude of the present work is to investigate the role of the stent on the hemodynamics of the blood stream inside the aneurysm. In the current study, the two stages of interventions are assumed based on the neck vessel angle mentioned in Table The impacts of aneurysm deformation on the main hemodynamic factors of mean WSS, OSI, pressure and velocity are demonstrated in Table Figure Comparison of OSI contour for original and deformed aneurysms are displayed in Fig. Figure In this study, the impacts of the stent on the flow structure of the four ICA aneurysms are comprehensively investigated. The primary attention of this research is to visualize blood flow and compared hemodynamic characteristics of ICA aneurysms before and after aneurysm deformation. Computational Fluid dynamic is applied to simulate the blood stream inside the aneurysm and calculate hemodynamic factors, i.e. WSS, pressure and OSI on the aneurysm wall. The stent effect on two-stages of deformation is disclosed and explained in this work. Attained results indicate that deformation of the aneurysm considerably decreases the WSS on the aneurysm wall due to limited blood entrance. However, the value of OSI does not change in deformed aneurysms. Pressure contour on the aneurysm wall also indicates that the value of this factor does not alter considerably while its location varies by deformation.


To the editor,Nocturnal enuresis is a disorder characterized by intermittent urinary incontinence that occurs during periods of sleep for at least one episode per month for at least 3 months . These eThis pathophysiological picture is captured by sympathetic receptors of the Autonomic Nervous System, which cause greater cardiomyocyte activity, secreting B-type natriuretic peptide (BNP) by the ventricles, which stimulates natriuresis and diuresis in order to compensate for the vasoconstrictor systems. that are activated in these situations. This increase in BNP, due to the pathophysiological condition of OSA, causes inhibition of the secretion of antidiuretic hormone (ADH), which regulates diuresis through the reabsorption of water in the collecting ducts .The study by Ribeiro et al. , publishThe improvement shown for nocturnal enuresis in the study by Ribeiro et al.  was clinFrom this, due to the paradoxical effect of ADH and BNP, some considerations of the mechanism of effect of upper airway obstruction on nocturnal enuresis in children arise: the small clinical effect of the increase in BNP is enough to strongly increase the proportion of nights dry? Can the delay time in data collection between 90 and 120 days affect hormonal indicators mainly in the heterogeneity of the sample? Is there another factor involved?Therefore, we can conclude that airway clearance modifications had little clinical impact on the hormonal actions of ADH and BNP as collected.The Authors


Acute psychotic disorders are increasingly being diagnosed in people addicted to PASA part of these patients develops chronic psychotic disorders for reasons that still insufficently known.The aim of the study was to determine preventive potential of antipsychotics in the development of chronic psychotic disorders as well as possible side effects of theur use.The prospective retrospective qualitative study conducted in the period Septmeber 2017-September 2022.Data from medical records and electronic databases were used in the study.A structured questionnare for conductin research,a clinnical psychatic inteview,MMPI 202,tests to determine of ilegal PAS in body flluids.According to the results of the study adequate treatment of the underlying desease,fewer or complete abscence of relapses,social and psychoteraapeutic support had the greater effects.In the group of opiate addicts an adequate dose of supstitution therapy it often played a crucial role.In experimental conditions the hypotesis about the preventive effect of antipsychotics on the development of psychotic disorders in peoplle addicted to PAS.On the contrary a whole series of new questions has beenopened.None Declared


Cancers highlights interdisciplinary research that applies physical science principles and approaches to the study of cancer biology.Dysregulated cellular processes drive malignant transformation, tumor progression, and metastasis, and affect responses to therapies. While much is known about the biochemical and genetic drivers of these processes, less is understood about the influence of biophysical properties on oncogenesis. This Special Issue of The research articles presented in this issue address a broad range of both basic and translational cancer biology problems. A central theme at the crossroads of tumor biology and biophysics is the role of the extracellular matrix (ECM) and mechanical forces in modulating cell behavior. We first present an article by Druzhkova et al.  that exaThe following three articles take a biophysical approach to developing new cancer treatment strategies. Mathews et al.  sought tDysregulation can occur at various levels, from single molecules to cell populations. This Special Issue concludes with two reviews that investigate the biophysical properties of proteins in the promotion of oncogenic signaling. A review from the Renz laboratory elaborates on the role of protein distribution and dynamics in differentiating normal cells from cancer cells, with a focus on comparing beta-catenin and CapG in gynecological cancers . The rolCancers contains exciting examples of how biophysical approaches can provide new insights into oncogenic processes. One of the key contributions of biophysical approaches is the ability to investigate intact and living cells at multiple spatiotemporal scales. Thus, the continued incorporation of biophysical perspectives and techniques into the field of cancer biology will undoubtedly advance our mechanistic understanding of oncogenesis and facilitate the development of novel therapeutic targets and combination therapies.The collection of articles in this Special Issue of


Imaging Mueller polarimetry is capable to trace in-plane orientation of brain fiber tracts by detecting the optical anisotropy of white matter of healthy brain. Brain tumor cells grow chaotically and destroy this anisotropy. Hence, the drop in scalar retardance values and randomization of the azimuth of the optical axis could serve as the optical marker for brain tumor zone delineation.The presence of underlying crossing fibers can also affect the values of scalar retardance and the azimuth of the optical axis. We studied and analyzed the impact of fiber crossing on the polarimetric images of thin histological sections of brain corpus callosum.We used the transmission Mueller microscope for imaging of two-layered stacks of thin sections of corpus callosum tissue to mimic the overlapping brain fiber tracts with different fiber orientations. The decomposition of the measured Mueller matrices was performed with differential and Lu–Chipman algorithms and completed by the statistical analysis of the maps of scalar retardance, azimuth of the optical axis, and depolarization.Our results indicate the sensitivity of Mueller polarimetry to different spatial arrangement of brain fiber tracts as seen in the maps of scalar retardance and azimuth of optical axis of two-layered stacks of corpus callosum sections The depolarization varies slightly (The crossing brain fiber tracts measured in transmission induce the drop in values of scalar retardance and randomization of the azimuth of the optical axis at optical path length of  In case a residual brain tissue with malignancy is left without treatment, tumor recurrence and the survival of a patient will be at stake.In this study, we explore the impact of brain fiber crossing on the polarimetric maps of scalar retardance, azimuth of the optical axis, and depolarization. We measured the stacks of differently oriented thin histological sections of human brain corpus callosum with the transmission Mueller microscope, because the corpus callosum serves as a connection between the two brain hemispheres and has a well-defined orientation of fiber bundles.22.1We used a formalin-fixed human brain obtained from the autopsy of an anonymous donor. A waiver for ethical approval was obtained from the Ethics Committee of the Canton of Bern (BASEC-Nr: Req-2021-01173). We excised a The schematics of the spatial arrangement of corpus callosum thin sections during the measurements with transmission Mueller microscope see Sec.  is preseparallel , then crparallel  and finaparallel .The presence of glass slides did not affect our measurements, because the measured Mueller matrix of glass without tissue was close to that of air , with the errors in normalized Mueller matrix elements 2.2A custom-built Mueller microscopeWhite-light 2.8 W light-emitting diode (LED) was chosen as a light source followed by a band-pass color filter  20 nm) to select the wavelength of a probing light beam. A ,Both the polarization state generator (PSG) and the polarization state analyzer (PSA) are comprised of the identical optical elements, but arranged in a reverse order. In short, they include a linear polarizer and two ferroelectric liquid crystal (FLC) retarders (Meadowlark FPR-200-1550) with a quarter-wave retarder placed between them. By varying the voltage applied to the FLC retarders, the orientation of their fast optical axis is switched between 0 deg and 45 deg. This approach for polarization modulation assures the generation of all optimal polarization states required to obtain the complete Mueller matrix of a specimen under study. The light scattered from a sample is collected by another objective , one can use the following mathematical representation: 3.2A decomposition algorithm, first proposed by Lu and Chipman4The corpus callosum in a human brain acts as a bridge connecting its two hemispheres. It consists of distinct fiber bundles that are oriented in a specific well-defined manner. In order to verify the presence and preferential orientation of the nerve fibers in studied samples, It is worth to mention that the TPEF microscopy measurements were taken at a different site of the corpus callosum tissue compared to the Mueller microscopy measurements see . However4.1We measured the Mueller matrix images of a single stripe of corpus callosum of ,Then we measured the stack of two superimposed stripes of corpus callosum ( deg see  and plot4.2It was demonstrated that the myelinated nerve fiber bundles display negative form birefringence.The corresponding box-whisker plots of the azimuth of the optical axis are shown in ssue see . The aziThe box-whisker plots of the azimuth distribution for the stack of two parallel (The spread of data is much larger for the distributions of the azimuth calculated for the corpus callosum stripes overlapped at 45 deg and 90 deg. The randomization of the azimuth values and the drop of total scalar retardance values serve as the indicators of the loss of optical anisotropy of the last two-layered stacks of corpus callosum.4.3The maps of the depolarization calculated using either differential or Lu–Chipman decomposition applied pixel-wise are shown in The lowest depolarization values account for a single layer of corpus callosum see , while t stripes .The box-whisker plots of the distributions of total depolarization are shown in 5In our study, the thin histological sections of human brain corpus callosum were arranged in different spatial configurations to measure their polarimetric response with the custom-built transmission Mueller microscope that was designed, aligned, and calibrated to measure the complete Mueller matrices of the samples under study. The two-layered stack (To extract the polarization and depolarization properties of the brain corpus callosum specimens, two different types of decomposition algorithms were used, namely the differential and Lu–Chipman decompositions. The former assumes the continuous variation of the polarization and depolarization properties of a medium, while the latter makes use of their sequential appearance. It makes the differential decomposition particularly suited for the post-processing of Mueller matrices of biological tissues that usually represent the complex structures with spatially intermixed polarimetric properties. However, the differential decomposition works well in transmission configuration, but may fail to process the Muller matrix data recorded in reflection, as for highly scattering media it may lead to the calculations of the logarithm of a negative number. The Lu–Chipman decomposition works well on the Muller matrix data recorded in both transmission and reflection configurations. The latter configuration is the only one relevant for the clinical applications of the imaging Mueller polarimetry operating in a visible wavelength range. Hence, the equivalence of the results obtained with the Lu–Chipman and differential decompositions in transmission configuration supports the use of the former algorithm for the interpretation of the Mueller matrix data of biological tissues recorded in reflection.It was found out that the net scalar retardance of the stack of two thin stripes of corpus callosum decreases with the increase of fiber crossing angle between two overlapped sections of brain corpus callosum tissue. This effect is explained by the partial compensation of the phase shift acquired by polarized light passing through the first stripe by the phase shift of the opposite sign acquired through the second stripe with different preferential orientation of the fibersOur prior studies demonstrated that the maps of the azimuth of the optical axis allow us monitoring a preferential 2D orientation of the fiber bundles at the site of the measurement in reflection configuration. The analysis of the azimuth images of Two-layered stack of corpus callosum stripes (Similar values of scalar retardance and azimuth of the optical axis were obtained for all spatial arrangement of corpus callosum sections with both decomposition algorithms, while higher values for the total depolarization parameter were obtained with Lu–Chipman decomposition. Hence, the choice of decomposition algorithm seems to be of non-negligible importance for the final results and the decomposition algorithm should be selected properly, in accordance to the experimental configuration, samples’ type and initial assumptions.The results of our studies demonstrate that significant drop of retardance values and randomization of the azimuth in combination with almost constant depolarization values (variation in vivo applications of imaging Mueller polarimetry in neurosurgery. The estimation of light penetration depth within the white matter of brain in reflection configurations is the subject of our ongoing studies.Achieving this goal will be of significant importance for


Frontiers in Medicine introduced the idea of bundling several papers dealing with similar or related problems into so-called Research Topics. It is expected that this editorial concept might convey an organized, inter-linked overview of related research results to the readers. This concept provides additionally the possibility to make functional connections between research projects which are anchored in different scientific disciplines. Such combined presentation helps to broaden the scientific horizon of experts working in different fields, and supports the interpretation of their results in wider scientific and social context. This special collection has published eight manuscripts of researchers from different countries and continents reporting examples of the latest knowledge in regulatory science. The goal of our selection was to cover a broad variety of regulatory challenges emerging in connection with the development of various nucleic acid-based drugs, oncological agents, the evidence-based evaluation of herbal medicinal products, the impact of pharmacogenetic programs on healthcare and finally linking marketing approval to the speed of pricing and reimbursement decisions.Chiu et al. wrote an extensive overview of the tasks and activities of the U.S. Food and Drug Administration (FDA) Division of Applied Regulatory Science (DARS). This division consists of interdisciplinary teams developing primarily modern biological methods for improving in vitro assessment of drugs effects. The publication describes several examples of new types of assays supporting regulatory decision making.Chisholm and Critchley from Australia argued that the rapid development of artificial Intelligence (AI) and machine learning techniques will dramatically influence the future work of regulatory experts. According to their review, it is mandatory to prepare the personnel to use efficiently and critically these possibilities for leading to successful international cooperation of regulatory agencies in adapting their work to the changing scientific environment, geopolitical shifts, pandemics, shortage of raw materials and interruptions of supply chains.McDermott et al. called attention to future importance of large scale pre-emptive panel genetic testing of many individuals for common pharmacogenetic variants underlying diseases. This genetic information could be stored in medical records and used if needed to select individualized targeted therapy for such diseases. Lack of knowledge, and the cost of the intervention were found to be the main barriers for implementing this program. Early leadership engagement, positive institutional culture, engaging stakeholders, and the selection of clinical champions were considered as facilitators to implement such pharmacogenetic service.Guerriaud and Kohli. They flagged some of the currently recognized disparities of categorizing similar products into different categories because of their different origins. In addition, the regulatory status of RNA drugs is differently defined by the EMA and FDA which obviously makes the international registration strategy difficult. The authors suggested some proposals for improving future classification based on updated definitions and recommended steps towards an international harmonization.The intriguing problems of the regulatory classification of the rapidly enlarging group of RNA drugs with quite different biological mechanisms of action was discussed by Zhou et al. described a recently initiated new program that used modern comparative clinical trial methodology to provide solid scientific background for characterization of efficacy and safety. Most of the phase II and III trials are prospective, double blind, randomized, parallel group trials. The results of these trials are expected to improve both the regulatory management and evidence-based use of these products in the clinical practice. According to the authors, the number of modern clinical trials is still small compared to the great wealth of the empirical knowledge.Over many centuries, China developed a rich collection of herbal medicines jointly referred to as Traditional Chinese Medicines. They were traditionally evaluated only empirically. Ilan describes an administration approach called “digital medical cannabis” which is based on the 2nd generation AI system able to modify the dose for optimizing individually patient benefit.The optimal use of herbal medicines depends on their standardization. Following the legalization of the cannabis market, many products with different amounts of active ingredients flooded the market. In addition, the intensity of the pharmacological effects and tolerance development are individually very different. Especially for effective patient care adjusting cannabis administration according to the needs of the patients is very important. Zhang et al. reported a systematic review comparing the time for oncologic drug approval following multi-regional clinical trials (MRCTs) as compared with single-country studies. MRCTs involving US, Europe and Japan lead to the shortest time for the approval of new oncological agents. The inclusion of additional regions prolonged the time for approval. Since bridging country trials need the least time, the authors recommend that additional single-country bridging studies be performed to shorten drug approval time if MRCTs do not apply.Gallo et al. analyzed the time needed for pricing and reimbursement decisions between 2018 and 2020 in Italy. They argue that the more than double time needed for decision making in case of new drugs is almost entirely due to the much longer health technology assessment procedure and related price negotiations.The time needed for pricing and reimbursement of drugs are influenced by the observed effect differences between the new and the available therapies, the clinical importance of the new agents as well as by the scientific quality of the clinical studies. We hope that combining these articles dealing with various aspects of drug development spanning from the bench to the patients, from the clinical studies through the regulatory decision and health technology assessment to the broad healthcare application will support the work of many colleagues active at various points of this complex process. Joint publication of these papers demonstrates that the decisions made at the different steps by various experts must consider the complexity of the entire process including also their social and ethical impacts.The draft and final version were prepared by SK-F. All authors contributed to the article and approved the submitted version.


According to the marked increase in the elderly population in Japan, an increasing number of patients were administered with anticoagulant agents, either for secondary prevention of ischemic stroke or primary prevention in patients with nonvalvular arterial fibrillation. Patients with hemorrhagic stroke or hemorrhagic conversion of ischemic stroke during anticoagulant therapy were reported to have poorer clinical outcomes owing to the difficulty in acute neurosurgical management, but the risk assessment for hemorrhagic events associated with anticoagulants in the central nervous system is not easy (2). The authors promptly performed the partial removal of hematoma with simultaneous administration of fresh frozen plasma, leading to an emergent reduction of intracranial pressure and then safely attempted radical decompressive craniectomy after the effect of apixaban had diminished. The authors’ two-stage management strategy was further justified by the continuous monitoring of intracranial pressure between first- and second-stage surgeries, and the favorable staged decompression was demonstrated by serial computed tomographic scans (2). While considering the recent advances in the neuroendoscopic modalities, the application of neuroendoscopic partial removal of the hematoma could have been a management option in the first-stage surgery in this case. It is necessary to evaluate the efficacy and safety of neuroendoscopic removal of intracranial hematoma in patients with anticoagulant administration in future studies.In this difficult clinical condition, the authors successfully managed a patient with massive hemorrhagic infarction during direct oral anticoagulant medication of apixaban by two-stage surgery using intracranial pressure monitoring (3). Based on the cumulative evidence, the most recent issue of the Japanese Guidelines for the Management of Stroke in 2023 recommends the administration of Andexanet alfa for the patients with hemorrhagic stroke using factor Xa inhibitors (Recommendation grade B) (4). Taken together, radical decompressive craniectomy with hematoma removal after the neutralization of factor Xa activity could be a management option if Andexanet alfa is available. Further investigation of a larger number of patients from multiple institutes is warranted to address this important issue.Recently, Andexanet alfa, a factor Xa inhibitor that neutralizes the anticoagulant effect of factor Xa inhibitors, including apixaban, became available in Japan. Although Andexanet alfa was not available at the time in this reported case, this neutralizing agent is expected to significantly contribute to the management of the patients with hemorrhagic stroke, including hemorrhagic infarction managed by factor Xa inhibitors, such as apixaban and edoxaban NoneMiki Fujimura is one of the Editors of JMA Journal and on the journal’s Editorial Staff. He was not involved in the editorial evaluation or decision to accept this article for publication at all.


The objective of the present study is to evaluate the anatomy of the inferior hypogastric plexus, correlating it with urological pathologies, imaging exams and surgeries of the female pelvis, especially for treatment of endometriosis. We carried out a review about the anatomy of the inferior hypogastric plexus in the female pelvis. We analyzed papers published in the past 20 years in the databases of Pubmed, Embase and Scielo, and we included only papers in English and excluded case reports, editorials, and opinions of specialists. We also studied two human fixed female corpses and microsurgical dissection material with a stereoscopic magnifying glass with 2.5x magnification. Classical anatomical studies provide few details of the morphology of the inferior hypogastric plexus (IHP) or the location and nature of the associated nerves. The fusion of pelvic splanchnic nerves, sacral splanchnic nerves, and superior hypogastric plexus together with visceral afferent fibers form the IHP. The surgeon’s precise knowledge of the anatomical relationship between the hypogastric nerve and the uterosacral ligament is essential to reduce the risk of complications and postoperative morbidity of patients surgically treated for deep infiltrative endometriosis involving the uterosacral ligament. Accurate knowledge of the innervation of the female pelvis is of fundamental importance for prevention of possible injuries and voiding dysfunctions as well as the evacuation mechanism in the postoperative period. Imaging exams such as nuclear magnetic resonance are interesting tools for more accurate visualization of the distribution of the hypogastric plexus in the female pelvis. The hypogastric plexus is responsible for the autonomic innervation of the pelvic viscera. Injury to these nerves during surgical interventions can be associated with voiding dysfunctions and the evacuation process. Knowledge of the anatomy of the hypogastric plexus is very important in female pelvic surgeries, especially operations for the treatment of endometriosis. Endometriosis is a pelvic dysfunction in women that requires a delicate and thorough surgical approach. The surgeon must have skill and knowledge of this region in order to avoid injury to the viscera, vessels and nerves of the pelvis. In recent times, laparoscopic and robotic surgery have greatly improved the visualization of the anatomical structures of the pelvis during these procedures -3.Classical anatomical studies provide few details about the morphology of the inferior hypogastric plexus (IHP) or the location and nature of the associated nerves. The aim of the present work is to evaluate the surgical anatomy of the hypogastric plexus through a narrative review of the literature, highlighting its importance during diagnosis and its approach during surgical procedures for the treatment of endometriosis.In this study we carried out a review of the anatomy of the inferior hypogastric plexus in the female pelvis. We analyzed papers published in the past 20 years in the databases of Pubmed, Embase and Scielo, found by using the key expressions “Hypogastric plexus”; “Inferior hypogastric plexus”; “MRI”; “Endometriosis”; “Robotic surgery”; and “Laparoscopic surgery”. We found several papers in these databases and we included only papers in English and excluded case reports, editorials and opinions of specialists .We also studied two human fixed female corpses and microsurgical dissection material with the aid of a stereoscopic magnifying glass with 2.5x magnification. A detailed dissection of the female pelvis was performed, identifying the superior hypogastric plexus at the level of the sacral promontory and its distribution in the female pelvis.The autonomic innervation of the pelvis originates from the continuation of the aortic plexus in the downward direction. Fibers of the inferior mesenteric plexus, situated below the inferior mesenteric artery, receive sympathetic fibers from the paravertebral trunk. Anterior to the fifth lumbar vertebra and in the region of the sacral promontory, these fibers unite with branches of the lower lumbar splanchnic nerves and form the so-called superior hypogastric plexus (SHP) or presacral nerve , 5. The The SHP divides anteriorly to the sacrum into two narrow and elongated networks with variable diameter, just below the sacral promontory, giving rise to the presacral nerves, better known as hypogastric nerves, which in general gather in a trunk and are called the hypogastric nerves (right and left) . The hypThe hypogastric nerves have an important relationship with the internal iliac vessels, being located medially and inferiorly to them, surrounded by retroperitoneal fat, also maintaining a relationship with the sigmoid colon on the left side and the rectum before the inferior hypogastric plexus is formed. Each nerve or hypogastric nerve passes inferiorly over the lateral part of the rectum (or the rectum and vagina in women). In the inferior and anterior region of the sacrum, each hypogastric nerve receives the pelvic splanchnic nerves from the sacral roots from S2 to S4, giving rise to the inferior hypogastric plexus (IHP)  Figure-.The IHP is formed by the union of the hypogastric nerves with the pelvic splanchnic nerves (nerves of Eckhardt) in the region posterior and medial to the internal iliac artery (hypogastric artery) . The disThe IHP branches out maintaining important relationships with the pelvic viscera in women. The ureter is an essential positional reference for the IHP: not in terms of its superior angle, the distance to which to the ureter is variable, but in terms of its top, in other words its (anterior) inferior angle: in all cases this top is at the ureter’s point of contact where it perforates the posterior layer of the broad ligament. In the region of the intersection with the uterine artery, branches of the IHP originate and go to the bladder and vagina . Two groIn the dissected parts, we observed that the superior hypogastric plexus was divided into right and left hypogastric nerves in the sacral promontory region and the pelvic splanchnic nerves joined these nerves, forming the IHP. In turn, the IHP originated fibers that innervate the viscera of the anterior and posterior compartments of the pelvis. There are few imaging-related studies enabling visualization of the pelvic region .The radiologist’s role in the management of endometriosis is becoming increasingly important as more centers move towards the use of female pelvic MRI exams to diagnose, delineate, or follow-up endometriosis lesions . The EurIt is important to diagnose endometriosis and thoroughly assess its extent, especially when surgical treatment is being considered. Magnetic resonance imaging (MRI) is a careful examination and interpretation technique that allows more accurate and complete diagnosis and staging than ultrasonography, especially in cases of deep pelvic endometriosis. In addition, MRI can identify implants in hard-to-reach places in endoscopic or laparoscopic explorations .MRI has been used routinely in patients with suspected deep endometriosis, where it and can identify lesions in different sites in a single evaluation, allowing assessment of the extent of the disease. MRI is also an effective technique for the preoperative diagnosis and staging of deep infiltrative endometriosis (IEM). However, the usefulness of MRI, because of sequences susceptible to chronic blood degradation products such as T2*-weighted images, remains uncertain . In an ilevator ani muscle, round ligament and bladder ; lateral surface of the rectum; pelvic ureter; and particularly the region of the crossing with the uterine artery, pararectal space, paracervix, hypogastric artery, piriformis muscle,  bladder .During the performance of pelvic endometriosis surgeries, whether laparoscopic, conventional or robotic, knowledge of the relationships between the hypogastric plexus and the pelvic viscera is of great importance. Endometriosis is a disease defined by the presence of endometrial tissue outside the uterine cavity. It is a progressive disease, without a clearly established etiopathogenesis, influenced by genetic and environmental factors . The disThe identification and prompt treatment of endometriosis are essential and are facilitated by precise clinical diagnosis. Endometriosis is classically defined as a chronic gynecological disease characterized by the presence of tissue similar to the endometrium outside the uterus. It is believed to arise due to retrograde menstruation. However, this description is outmoded and does not reflect the true scope and manifestations of the disease. The clinical presentations are varied, the presence of pelvic lesions is heterogeneous and the manifestations of the disease outside the female reproductive tract remain poorly understood. Endometriosis is now considered to be a systemic disease instead of a disease that predominantly affects the pelvis .Of the pathogenic theories proposed , none explains all the different types of endometrioses. According to the most convincing model, the hypothesis of retrograde menstruation, endometrial fragments that reach the pelvis via the retrograde transtubal flow become lodged in the peritoneum and abdominal organs and proliferate and cause chronic inflammation with the formation of adherences . The lesIn robotic surgery, pelvic autonomic nerves end up being easier to identify with the magnification provided by an endoscopic camera . These sZakhari et al.  carried The superior hypogastric plexus has been described along with the hypogastric nerve, the most superficial and easily identifiable component of the inferior hypogastric plexus. It was identified and used as a reference point to preserve the autonomous bundles in the pelvis. The following steps, illustrated with laparoscopic images, describe a surgical technique designed to identify and preserve the hypogastric nerve and deeper inferior hypogastric plexus without the need for more extensive pelvic dissection to the level of the sacral nerve roots:  transperRobot-assisted nerve-plane-preserving eradication of deep endometriosis is as technically feasible as the conventional laparoscopic approach. The step-by-step technique should help surgeons perform each part of the surgery in a logical sequence, making the procedure easier and safer to complete. However, the latent benefits of robot-assisted nerve-sparing surgery in the treatment of deep endometriosis remain unclear .A meta-analysis confirmed that robotic surgery is safe and feasible in patients afflicted with endometriosis. The articles examined suggested that robotic surgery is a valid option and can be considered an alternative to conventional laparoscopic surgery, especially in advanced cases .The precise knowledge of the innervation of the female pelvis is of fundamental importance for prevention of injuries, voiding dysfunctions and problems in the evacuation mechanism in the postoperative period. Imaging exams such as nuclear magnetic resonance are an interesting tool for more accurate visualization of the distribution of the hypogastric plexus in the female pelvis.


The contrast betweenthe proposed model and the results showed that the direct influence of ITsecurity influences the government’s attitude toward COVID-19 and DTimplementing actions to achieve SDGs. The findings of this work are of greatvalue both for the actors involved in the design and implementation of publicpolicies and for those responsible for local governance in their objective toimprove citizens’ experience of the services provided and in exceptionalsituations such as the one experienced as a result, of-COVID-19.This paper analyzes how Digital Transformation (DT) processes have influenced theAttitude of local governments (LGs) toward the COVID-19 pandemic and theireffect on achieving the United Nations’ Sustainable Development Goals (SDGs).The data were collected from LGs in Spain ( The public sector, especially local government (LG), is currently immersed in aperiod of constant transformation and uncertainty to which it must respond withradical changes to meet the needs of its citizens .As has already happened in business, citizens  demand that the public sector undergoes a similar approach .Such a Numerous research studies examine the effect of collaboration on innovation success.This is the case of the review of the mediating role of social performance betweencooperation and innovation performance conducted by The adoption of social performance techniques in industrial companies is expected toincrease significantly over the next 10 years. A consequence of this will be thatmanagers can promote sustainable innovation by collaborating with consumers andimproving the social performance of their companies . For exaDT in the public sector is not necessarily voluntary. It is often imposing, as LGsare forced to adopt digital innovation to meet the requirements of reforms launchedat the national or supranational level . This waThe SDGs represent the commitment of world leaders to act on a more sustainable pathtoward inclusive and equity growth-able. Electronic government actions based on DTshould favor the generation of a new paradigm in providing services throughweb-based functionalities and ICTs . InrespThis paper addresses and analyzes the DT processes implemented by LGs in Spain from adouble perspective: their influence on the achievement of the SDGs and the attitudeof LGs and their employees during the COVID-19 pandemic. To achieve this objective,we have examined how LGs and their employees have adopted and integrated newelectronic and digitalization processes into their daily tasks to effectively andefficiently interact with citizens. The proposed model was tested with theparticipation of 124 Spanish LGs. The results showed the direct influence of ITsecurity on attitude toward COVID-19 and that of DT on implementing actions toachieve SDGs. This study found that DT processes in LGs were relevant in attainingSDGs and instrumental in resolving the difficulties raised in the relationshipbetween LGs and citizens due to COVID-19.The contrast of the influence exerted by manageable elements of the local governmentsthemselves, such as the IT skills of their workers and the actions of IT securityand DT in the context of potentially facilitating conditions for aligning efforts inmoments of great uncertainty such as those experienced during COVID-19, constitutesone of the main contributions of this work.DT processes and the implementation of e-services in the public sector is anuanced reality that is difficult to define . AccordiWithin any organization, transformation, and change in the way it relates to itsclients or users may be conditioned by the dimension of variables such asflexibility and the extent of bureaucracy it entails , and theIn the case of a DT process in an LG, size can be fundamental to achieving theproposed objectives when providing electronic resources for citizens . In mostThe link between the organization’s dimension and innovation is common inresearch on innovative processes and management . Small aCitizens’ expectations regarding the public services provided by LGs and theirfinancial management have given rise to many codes of conduct and ethicaldeclarations to optimize financial and budgetary resources .Codes oTrust seals have a similar objective but depend on an external entity. Thepossession of these seals increases user confidence and is linked to the use ofgood practices by the organization . Such seThe relevance of the budgetary dimension, along with codes of conduct and trustseals and conditions LGs when it comes to accessing resources, acquiringknowledge, and implementing innovative actions that improve the servicesprovided and the working conditions of their employees. Based on the above, wecan establish the following research hypotheses:H1 (+): The facilitating conditions based on the budgetarydimension and codes of conduct and trust seals exert a direct andpositive influence on implementing digital transformation actions inlocal governments.H2 (+): The facilitating conditions based on the budgetarydimension, codes of conduct, and trust seals exert a direct andpositive influence on the acquisition of resources and knowledge inthe field of Information and Communication Technologies in localgovernments.The budgetary dimension of LG can limit access to and use of ICTs and publicemployees in performing their regular tasks . This meWithin LGs, as in any organization, the security of information systems is acrucial element that is constantly evolving. This requires that the staff gainthe knowledge and technological skills to manage the safety of the informationsystems used in developing their tasks . Such knThe fundamental value of the IT skills acquired by LG personnel for theimprovement of information systems security, together with the achievement ofthe objectives set by the public administration, led us to establish thefollowing two research hypotheses:H3 (+): The acquisition and availability of knowledge and skillsin using technology to perform the usual tasks of local governmentworkers exert a direct and positive influence on the digitaltransformation actions implemented.H4 (+): The acquisition and availability of knowledge and skillsin the use of technology for the performance of the usual tasks oflocal government workers exert a direct and positive influence onthe security of the information systems used.The need for LGs to plan financially and strategically plan well in advance makesit difficult for municipalities and their staff to adapt to technological andenvironmental changes . This shEffectiveness and efficiency in the provision of public services by LGs throughDT are related to the favorable alignment of the actions of publicadministrations with the balanced development in social, economic, andenvironmental sustainability advocated by the SDGs .Thanks to the radical decrease in the cost of collecting, storing, and processinginformation , DT offeHow DT enables LGs to take actions to achieve sustainable development (in itsthree dimensions) led us to establish the following research hypothesis:H5 (+): Digital transformation actions by local governmentsenable the provision of public services effectively and efficientlyaligned with Sustainable Development Goals.One of the consequences of the DT actions carried out by the LGs has been theincrease in the security measures adopted to protect the information systems andresources used in the provision of services . The incThe importance attached by LGs to the security of their information systems,along with the increasing implementation of protocols to increase certainty andtrust ,has broInformation systems security has been vital during the COVID-19 pandemic due to tBased on the verification of the importance of the security measures adopted byLGs for the information systems used by their employees to deliver services tocitizens, the following research hypothesis was established:H6 (+): Improvement in the security of the information systemsof local governments exerts a direct and positive influence on theattitude of workers when carrying out their tasks during theCOVID-19 pandemic.The contrast of the conceptual model proposed in N = 8,131; The methodology for collecting the data and information was a questionnairedistributed to the total number of LGs in Spain in 2020 may be due to one of the following reasons:Municipalities’ usual problem lies primarily in the need for more resources andtraining of public employees. However, the low response rate may be owing to theneed for more collaboration and coordination between different departments,municipalities, and other government agencies. Undoubtedly, this study addressesa sensitive issue because municipalities’ lack of adaptation to new technologiescan affect their ability to provide adequate services, which is a fact that isnot easy to recognize.The exogenous latent variable of the proposed model and the questionnairewas:Facilitating Conditions. These were grouped into threeitems: the municipality government budget, measured on a scale of 4budget intervals, as shown in - The last item used was the degree of use of information systems audits thatenable trust seals. These audits depend on a second entity that auditscompliance with the standards that give rise to the seal.The endogenous variables proposed in the model were:IT Skills: This latent variable was measured based onthree items referenced in the competencies of the Digital CompetencyFramework 2.0 . This type of analysis is well-suited for exploratory analysis.The partial least squares regression technique is considered convenient formodeling structural equations based on variance and is recommended for socialsciences, specifically in the study of organizations .The performance of the PLS-SEM analysis followed recommendations for reflectiveor B-mode constructs . First, Secondly, the construct reliability and validity were analyzed . TheCroR2 , 9 , 10 , and 11 (Sustainable Cities andCommunities).Another relevant conclusion of this work is the relevance of technological securitymeasures and processes in information systems perceived by LG employees. This willencourage a better employee attitude in situations arising from COVID-19.Regarding the implications for the theory of the results of this work, it isessential to emphasize the relevance of certain (facilitating) conditions withinLGs. These affect the DT and IT security processes, particularly as determinantsin current challenges such as the implementation of SDGs and the situationevolving because of COVID-19.The results of this work allow us to establish that the facilitating conditions,based on the budgetary dimension, and the protocols and trust seals (due to thedirect and positive influence that they have on the actions that the LGs take)favor DT and on the potential for their workers to acquire knowledge andtechnical skills. These enabling conditions indirectly influence, through DT andIT skills, the achievement of the SDGs by LGs and the attitude of workers towardCOVID-19.The practical implications derived from this work for the actors and agentsinvolved in the design and implementation of public actions and policies showthe importance not only of the development of end-user policies but also thatthese must address previous issues that will favor the achievement of theobjectives pursued.The main benefit of this study is that it provides a detailed understanding ofhow digital transformation processes have influenced the attitude of LGs towardthe COVID-19 pandemic and the achievement of the SDGs.Like all scientific research, aspects of this work need to be improved, such asthe sample size of LG respondents concerning the total population under study.This urges caution when establishing possible extrapolations of the results tothe totality of LGs. Another potential limitation is the national nature (Spain)of the LGs analyzed. Spanish LGs have some particular characteristics, such astheir unitary political system in which the central government has great powerover the policies and services of LGs. In contrast, LGs have greater autonomy inother European countries, such as Germany or the United Kingdom.Another particularity is the usual more precarious financial situation than inother European countries due to the need for more financial resources anddependence on central government funds. And finally, a centralized managementmodel, with a great weight of bureaucracy and a lack of citizen participation,while in other European countries, such as the Netherlands or Denmark, there aremore decentralized and participatory management models. Future research couldinclude municipalities in European countries.Regarding potential future research lines, local governments’ budgetarydimensions could be analyzed comparatively in terms of the different budgetsizes. Still, with similar DT and IT, security actions are undertaken.


Membrane dialysis is one of the membrane contactors applied to wastewater treatment. The dialysis rate of a traditional dialyzer module is restricted because the solutes transport through the membrane only by diffusion, in which the mass-transfer driving force across the membrane is the concentration gradient between the retentate and dialysate phases. A two-dimensional mathematical model of the concentric tubular dialysis-and-ultrafiltration module was developed theoretically in this study. The simulated results show that the dialysis rate improvement was significantly improved through implementing the ultrafiltration effect by introducing a trans-membrane pressure during the membrane dialysis process. The velocity profiles of the retentate and dialysate phases in the dialysis-and-ultrafiltration system were derived and expressed in terms of the stream function, which was solved numerically by the Crank–Nicolson method. A maximum dialysis rate improvement of up to twice that of the pure dialysis system ( Membrane extraction ,2, membrThe dialysate phase concentration in a dialysis process does not remain unchanged and the solvent is inevitably to pass through the membrane, across which exists a pressure gradient between two phases besides the other membrane contactors. Early studies focused on a simplified analysis by ignoring the concentration variance of the dialysate phase and assuming no solvent passed through the membrane ,18. A twThe phenomena of suction or injection through the membrane due to the ultrafiltration operation will lead to a complex flowing pattern in the channels of a membrane dialyzer, in which the velocity distribution can be solved using the stream function coupled with the perturbation method ,34. A twa (retentate phase) and annular subchannel b  with inner radius A hydrophilic membrane with thickness a and annular subchannel b under the assumed conditions as follows:The velocity distributions were derived with the use of the continuity equations and momentum balance equations in both inner subchannel The dimensionless forms of the velocity distributions, Similarly, the dimensionless forms of velocity distributions in the annulus subchannel, a, b and m refer to the retentate, dialysate and membrane phases, respectively; The mass transfer equations in the retentate, dialysate and membrane phases were derived in the concentric tubular dialyzer with the ultrafiltration system, as shown in The solute in the membrane phase is simultaneously transported by convection and diffusion due to the dialysis-and-ultrafiltration operation, as shown in The general solution of Equation (22) isOne obtains Equations (24) and (25) for Thus, the solute concentration distribution By substituting Equation (27) into the boundary conditions of Equations (17) and (19), the derivatives of Hence, the two-dimensional solute concentration distributions of a concentric tubular dialysis-and-ultrafiltration operation can be solved by the governing equations, Equations (11) and (12), with the use of the boundary conditions of Equations (14), (15), (20), (21), (28) and (29).A concentric tubular dialysis system without ultrafiltration operations, that is, a (retentate phase) and annular subchannel b , respectively, except for incorporating The velocity distributions are the same equations, that is, Equations (7) and (8) and Equations (9) and (10), for the inner subchannel The solute in membrane phase is transported by diffusion only, as shown in Integrating Equation (41) twice to obtain the general solution asThus, the solute concentration distribution By substituting Equation (44) into the boundary conditions of Equations (36) and (38), the derivatives of Hence, the two-dimensional solute concentration distributions of a concentric tubular dialysis-and-ultrafiltration operation can be solved by the governing equations, Equations (30) and (31), with the use of the boundary conditions of Equations (33), (34), (39), (40), (45) and (46).The mass balances of Equations (11) and (12) and Equations (30) and (31) were made for membrane dialysis along the flowing direction with and without ultrafiltration operations, respectively. Thus, the solute concentrations in both the inner and annular streams were solved numerically using the Crank–Nicolson method. The availability of computing software facilitates the numerical solution for this problem, in which the node numbers in the The dialysis rate of the dialysis system with and without the ultrafiltration operation is defined asFurthermore, the dialysis rate improvement The velocity distributions of The two-dimensional theoretical model of the concentric tubular dialyzer with and without ultrafiltration operations was solved numerically using the Crank–Nicolson method, for which the convergence tolerance of the numerical solutions is shown in The influences of the ultrafiltration rate A smaller volumetric flow rate of retentate phase results in a lower concentration distribution due to the increase in the residence time for transporting the solute from the retentate phase to the dialysate phase, as shown in The influence of ultrafiltration rates and the retentate phase flow rates on the average concentrations of both the retentate and dialysate phases are presented in Similarly, the influences of various ultrafiltration rates and volumetric flow rates of the dialysate phase on both the retentate and dialysate phases are presented in The average outlet concentrations of the retentate phase The effect of the channel thickness ratio The solute is transported through the membrane by two mechanisms in a dialysis module with ultrafiltration operation: (a) diffusion (caused by the concentration difference across the membrane) and (b) convection (caused by the ultrafiltration operation). The dialysis rate The results show that the dialysis rate For the same reason as refers to the increase in the convective mass-transfer coefficient, the dialysis rate The experimental work is cost prohibitive at the present time and there is only the available experimental data from the flat-plate dialyzer for confirmation. The present study could be analogized from those in our previous work on the flat-plate module ; this isdialyzer  for compThe dialysis efficiency The dialysis efficiency The influence of the membrane sieving coefficient on the dialysis efficiency The dialysis rate improvements The dialysis rate improvements A concentric tubular dialyzer with ultrafiltration operation to augment the dialysis rate was investigated theoretically. Two-dimensional mathematical equations were developed and formulated to predict the dialysis efficiency and dialysis rate improvement in the dialysis-and-ultrafiltration system as compared with the module without the ultrafiltration operation, which was solved numerically using the Crank–Nicolson method. There were two innovation points of this module design: (1) a two-dimensional mathematical model of the concentric tubular dialyzer was developed theoretically; (2) the simulated results show that the dialysis rate improvement was significantly improved with implementation of the ultrafiltration effect. A more direct method provides a straightforward strategy to the solution for determining the effect of the channel thickness ratio, which allows the specification setting by the designer to be met with economic consideration.Average concentration distributions of the dialysis system in the retentate phase decrease along the axial direction and with decreasing ultrafiltration rate whereas the average concentration of the dialysate phase increases with increasing ultrafiltration rate and the retentate phase flow rate.Both average concentration distributions in the retentate and dialysate phases decrease with the volumetric flow rate of the dialysate phase.The average concentration distribution of the retentate phase decreases with increases in both the membrane sieving coefficient and channel thickness ratio.The average outlet concentration of retentate phase increases with increasing retentate phase flow rate because the residence time is increased as well as with increasing ultrafiltration rate, channel thickness ratio and volumetric flow rate of the dialysate phase.The results show that the dialysis rate The dialysis efficiency The dialysis rate improvements Regarding the pure dialysis system without ultrafiltration operation, its dialysis efficiency could be readily enhanced by employing the module with ultrafiltration operation, especially for operations with lower volumetric flow rate of the retentate phase. A maximum dialysis rate improvement of up to twice was found in the module with the ultrafiltration rate The results demonstrate the technical feasibility of dialysis rate improvement in the tubular membrane dialyzer with ultrafiltration operation. It was also found that the concentrations of the components  in the retentate could be removed to reduce solutes in wastewater treatment processes, which depend on the separation technique and the operational parameters in membrane-based separation processes. In this paper, both the dialysis rate and ultrafiltration operation were examined from an economic perspective by implementing various ultrafiltration rates in the tubular dialyzer. Therefore, the alternative membrane sieving coefficient, membrane material and ultrafiltration rate require further investigation regarding the economic considerations of the tubular dialyzer. It is believed that the availability of such a simplified mathematical formulation as developed here is the value in the present work in designing a concentric tubular dialyzer and will be an important contribution to the design and investigation of multi-stream or multi-phase problems with coupling mutual boundary conditions. One may follow the present theory and develop a mathematical formulation to deal with multi-stream or multi-phase heat- or mass-transfer devices for each particular application with various geometries.


The aim of the study is identification of correlations between the serum concentrations of iron and the risk of breast and/or ovarian cancer among female BRCA1 mutations carriers.The subjects selected for the trial were Polish women, positive for at least one of three founder mutations in BRCA1 gene dominating in Poland . Persons with detected tumor were considered as cases and the others were considered as controls. One case and two controls were paired regarding many criteria  to achieve the maximum of similarity between them.The proportion of cases and control in the first quartile was taken as a reference to calculate the odds ratio, confidence interval and p-value of the multivariate conditional logistic regression.The iron was quantitatively measured by ICP-MS (Inductively Coupled Plasma Mass Spectrometry), .This study shows that concentration levels of iron in blood serum are a strong factors associated with an additionally increased risk of breast and ovarian cancer among BRCA1 mutation carriers.For iron concentration, all quartiles above the first one had a decreased risk of breast or ovarian cancer. The results are shown in Table Similarly, high ratios of iron to selenium were significantly associated with disease protection which is shown in Table


The CASCADE study was a pragmatic cluster RCT, with integral process and economic evaluations, of a complex psycho-educational intervention for young people with diabetes. The study was funded by the NIHR-HTA and carried out by a multi-institutional team .The extensive integrated multi-method process evaluation was planned prospectively and ran for the four years of the trial. The aims of the process evaluation were to 1) assess the feasibility and describe the provision of the CASCADE intervention within a standard clinic setting for a diverse range of young people; and 2) build on and help explain trial outcome findings and provide information on how the intervention might be modified.The process evaluation used a range of both qualitative and quantitative methods including observations of education sessions; interviews with a sub sample of young people, parents and staff; questionnaires relating to views of the intervention; attendance data and case note review.Currently there is limited published guidance on how to conduct a high quality integrated process evaluation that improves the usefulness of trial findings. In this presentation, members of the CASCADE process evaluation research team will provide a detailed example of carrying out such an evaluation. The presentation will include; the justifications for the methodological approach used, descriptions of context and sampling, data collection and analysis methods. Attention will be drawn to the specific methodological processes and practical facilitators employed to maximize the integration of trial and process components.


The evidence for Neanderthal lithic technology is reviewed and summarized for four caves on The Rock of Gibraltar: Vanguard, Beefsteak, Ibex and Gorham’s. Some of the observed patterns in technology are statistically tested including raw material selection, platform preparation, and the use of formal and expedient technological schemas. The main parameters of technological variation are examined through detailed analysis of the Gibraltar cores and comparison with samples from the classic Mousterian sites of Le Moustier and Tabun C. The Gibraltar Mousterian, including the youngest assemblage from Layer IV of Gorham’s Cave, spans the typical Middle Palaeolithic range of variation from radial Levallois to unidirectional and multi-platform flaking schemas, with characteristic emphasis on the former. A diachronic pattern of change in the Gorham’s Cave sequence is documented, with the younger assemblages utilising more localized raw material and less formal flaking procedures. We attribute this change to a reduction in residential mobility as the climate deteriorated during Marine Isotope Stage 3 and the Neanderthal population contracted into a refugium. When chipping stone to create sharp edged tools, there are a wide range of strategies that a knapper may employ. The factors influencing the choice of knapping strategy include downstream effects from the selection of particular types of stone and clast morphologies, as well as the cultural repertoire, foraging methods and mobility of the hominin group. Understanding knapping strategies can therefore inform us about several aspects of hominin behaviour. In this study we look at knapping strategies among a particularly iconic set of hominins: the Neanderthals of Gibraltar, who are both one of the most comprehensively studied and latest surviving of all Neanderthal populations.Homo sapiens over the last 100 thousand years. Gibraltar is home to some of the world’s most significant Neanderthal sites. The region is historically significant as one of the first discoveries of Neanderthal skeletal remains was made in Forbes Quarry in 1848 The Rock of Gibraltar is a limestone klippe peninsula at the southern tip of Iberia  and reprThe association between Mousterian technology and the Neanderthals is well documented across Europe and Gibraltar itself has played a role in establishing the link The Gibraltar caves have been subject to excavations by a number of teams. Previous studies of the lithic assemblages have documented artefact typologies, reduction sequences, spatial patterns and putative functions Various materials suitable for lithic manufacture are available on Gibraltar, the lowest quality of which is the limestone of The Rock itself. A quartzite outcrop occurs on the western side of The Rock, with primary sources of quartzitic sandstone available within 10km of Gibraltar In this article we examine artefacts from four different caves: Vanguard, Beefsteak, Ibex and Gorham’s . Each caVanguard Cave is one of a series of caves on Governor’s Beach, which is on the south-east side of Gibraltar. Optically Stimulated Luminescence (OSL) dating indicates Middle Palaeolithic occupation mainly took place during MIS 5, after which time the cave became filled with sand In the Middle Area of Vanguard cave three occupation horizons have been identified in situ knapping The intermediate occupation horizon contains two hammers of quartzite and one of sandstone, which, along with 46% of artefacts being smaller than 15 mm and the refitting of some chert flakes, suggests some In the upper occupation horizon the presence of two quartzite cobble hammerstones, one of which refits from two halves, suggests some knapping took place here The Northern Alcove in Vanguard Cave, which is approximately the same level as the three occupation horizons also contained artefacts of quartzite, chert (including red chert), and limestone, and is associated with a hearth éclat debordant on dark red chert, and were likely introduced as finished artefacts. It is suggested that some of these chert pieces were used as shucks for opening the associated shellfish 2 area, and they include refits and 997 artefacts <15 mm in maximum dimension. All these factors indicate that they represent a discrete knapping episode, with the low frequency of thermal modification showing that this took place after the associated fire had died down A hearth located in the upper part of Vanguard Cave, dated to 108.5 kya Beefsteak Cave is located near to Europa Point at the southern tip of Gibraltar. Uranium series dating of layer D, which overlies Middle Palaeolithic artefacts in layers C and B, produced a date of 98.8±15.5 kya Ibex cave is located high on the eastern side of Gibraltar about halfway along the length of The Rock. Tooth enamel from a layer underlying Mousterian artefacts was dated using Electron Spin Resonance to 37 kya (early uptake (EU)) or 49 kya (linear uptake (LU)) Adjacent to Vanguard Cave on Governor’s Beach is the larger Gorham’s Cave. Micromorphology indicates that he cave was occupied intermittently by both hominins and hyenas Based on stratigraphy, the Gorham’s Cave Mousterian sequence may be divided into six main phases. The lowermost phase contains few artefacts and is undated so will not be discussed further. The next phase comprises the upper Sands and Stony Lenses member (SSLm) which is divided into six subunits and may be correlated with Waechter’s layers L, M, O and P Overlying the Sands and Stony Lenses member is the Lower Bioturbated Sands member (LBSm), which has numerous coarse and fine facies. Five radiocarbon dates place the age of this member at c. 47.5 kya in situ knapping, with 39% of flakes having cortex The next member going up the sequence is the Bedded Sands (BeSm), which date to around 46 kya The most recent Mousterian member in the middle area of Gorham’s Cave is the Upper Bioturbated Sands member (UBSm). The three lower subunits of this member have Mousterian artefacts with radiocarbon dates for these subunits ranging from 45–34 kya Towards the back of Gorham’s Cave new excavations have uncovered Mousterian artefacts in a young deposit known as Layer IV Here we statistically assess the lithic patterns described above, including the variation in reduction techniques and raw material exploitation across the Mousterian of the Gibraltar Caves. We examine the diachronic variation in raw material selection, flake platform preparation and core reduction technology through the Gorham’s sequence.A total of 54 cores and assayed clasts from the four Gibraltar caves described above  were examined to quantify patterns in stone reduction technology in the Gibraltar Mousterian. The Middle Palaeolithic cores of Gibraltar are typologically characteristic of Neanderthal technology elsewhere e.g. The largest flakes from Gibraltar are made on the non-local honey coloured chert. To assess the differences in the use of this chert in comparison to the local varieties available on The Rock we examined artefact type frequencies from Gorham’s Cave . A chi-sIn Gorham’s Cave a pattern was observed whereby the use of more local and coarser grained materials appears to increase through time. Limestone is available in the cave itself, while quartzite occurs both as beach cobbles and as a now submerged primary outcrop in front of the cave. Chert, whilst sometimes procured as small beach pebbles, is generally more spatially restricted on The Rock, with some chert even procured from inland. We use a series of Fisher’s Exact tests to compare the proportions of coarser grained limestone and quartzite, with finer grained chert , betweenPlatform preparation is a parameter of investment in flake production, with higher proportions of platform preparation reflecting more formal production of flakes. Using Fisher’s Exact tests we assess the pattern of decreasing platform preparation through time in Gorham’s Cave, by comparing the proportion of platform preparation in sequential levels . There iet al.It has been suggested that the occupation of the Layer IV of Gorham’s Cave represents the early Upper Palaeolithic To obtain a statistical overview of the technological variation in the Gibraltar Mousterian we measured a suite of variables on the lithic cores. To put the Gibraltar cores in context we also measured cores from two classic Middle Palaeolithic sites: Le Moustier in France, the type site of the Mousterian, and Tabun Layer C, one of the best known Levantine Middle Palaeolithic assemblages. The variables measured were as follows: the percent of cortex remaining on the core; the number of flake scars; the proportion of blade scars; the length to width ratio of the core ; the width to thickness ratio of the core; the ratio of the proximal width to the distal width of the core; the lateral and distal curvature of the upper surface; the relative intersection height of the main flaking surface and the underlying surface; the mean platform angle; the number of platforms; the proportion of the perimeter of the upper core face that was faceted; the proportion of the core face covered by the length of the largest scar; and the scar pattern angle of the upper and lower faces Four components were extracted with Eigenvalues over 1, hence these factors explain a greater proportion of the variance in the input variables than any individual input variable. The first two components accounted for 28.9% and 18.5% of the variance respectively, so almost half the variance in the input variables is explained by these two components. The component matrix  shows thA scatter plot of the first two principal components shows how the cores from each assemblage are distributed . Most ofThe Mousterian technology of Gibraltar documents the use of the caves by Neanderthal populations during MIS 3, 4 and 5. The homogeneity in technology in Beefsteak and Ibex Caves and the presence of refits in the small assemblage from the latter, suggests that the occupation of these caves may be ascribed to single episodes. On the other hand, Vanguard Cave contains a longer sequence of stratified occupations with a greater variety of lithic assemblages; yet, low artefact densities and the presence of refits illustrates that individual occupations were relatively short-term. This accords with the evidence that the hearths at Vanguard were either used once, or used, abandoned and later reused In general we may describe three technological strategies employed by the Neanderthals of Gibraltar. The most formal involves Levallois reduction of large clasts of honey coloured chert from inland Iberia. Large Levallois flakes and some Levallois cores in this honey chert were then selected and carried over a distance of at least 17km to Gibraltar. The intermediate strategy comprises the exploitation of chert and quartzite from outcrops on and around The Rock by Levallois and discoidal reduction techniques, often with platform preparation. The third strategy involves the expedient single and multiplatform reduction of quartzite cobbles and chert pebbles from the beaches in front of the caves, or even using the limestone of the caves themselves. All three strategies are evident in the earliest dated occupation phases on Gibraltar from Vanguard Cave. The ephemeral Beefsteak and Ibex Cave occupations are characterised by the intermediate strategy. In Gorham’s Cave there appears to be a diachronic trend with the earlier levels focussed on the more formal strategies; then a shift towards expedient strategies in the later levels, with no non-local honey coloured chert unknown in the final phase of Mousterian occupation.The formal cores are significantly smaller and have higher flake scar densities than the informal cores, indicating they were more heavily worked. The three strategies appear to reflect different mobility patterns as the most formal technology is practised on the non-local material and the most expedient technology is used on the most immediately available material. Several researchers have correlated expedient forager technology with low mobility and formal forager technology with high mobility e.g. A GIS analysis of the Southern Iberian Mousterian showed that sites are concentrated both near the coast and along major rivers The optimal area for Late Pleistocene hominin occupation in southern Iberia, with the highest rainfall and temperature, and the greatest stability and diversity, would have been Gibraltar and its immediate environs Bio-climatic modelling indicates that the favoured habitats of the southern Iberian Neanderthals became fragmented during MIS3 separating coastal and upland populations Homo sapiens c. 37kya, there was also a reduction in Neanderthal range size with far fewer exotic materials being exploited than in the earlier Middle Palaeolithic Parallels may be found with MIS3 Neanderthals populations elsewhere. In the southern Caucasus the environment was stable and diverse, like Gibraltar, and also did not suffer the MIS3 deterioration to the same extent as surrounding regions sensu Henrich, Gibraltar has been hypothesized to be one of the last refuges of the Neanderthals with a date of 28 kya for the youngest Mousterian occupation in Layer IV of Gorham’s Cave The Mousterian record from the Gibraltar caves provides a rich sequence of Neanderthal occupation in an optimal habitat. The high biodiversity and stability of the Gibraltar climate may have allowed this region to act as a refugium for the last surviving Neanderthals


P-values obtained remain valid. In any case, this mistake does not affect the results and conclusions of the paper.The authors of the above research article have informed the journal that an error occurred during assembly of the graphs shown in Figure