The incidence of cholesteatoma occurring as a result of tympanoplasty is extremely rare. Understanding the cause and preventing its occurrence in the future is the main intention of highlighting this peculiar presentation.A 25-year-old woman presented with progressive hearing loss and blocked sensation in the left ear of one and a half months duration. Past history revealed a history of left myringoplasty six years prior to presentation. Clinical examination of the ear revealed a smooth, soft epithelium covered bulge in the lateral one-third of the floor and posterior wall of the left external auditory canal. HRCT and MRI of the temporal bone confirmed the presence of a soft tissue density in the mastoid. Pure tone audiometry revealed conductive hearing loss. She underwent mastoid exploration, removal of sac with soft wall reconstruction.Proper placement of the vascular strip with the skin lining the external auditory canal with approximation of the incision margins is essential to prevent iatrogenic cholesteatoma formation. Close follow-up is essential to prevent any recurrence and diffusion weighted MRI plays a vital role in detection of recurrence. Cholesteatoma is a sac containing keratinising squamous epithelium presenting in the middle ear and mastoid with a propensity to erode bone and cause complications intracranially and extracranially ,2. The iA 25-year-old woman presented to our out-patient department with progressive hearing loss and blocked sensation in the left ear for of one and a half months duration. There was no history of ear discharge, ear pain, vertigo and tinnitus. There was no history of nose or throat complaints. Past history revealed a history of left myringoplasty six years prior to presentation. Clinical examination of the ear revealed a smooth, soft epithelium covered bulge in the lateral one-third of the floor and posterior wall of the left external auditory canal which was sensitive to touch and did not bleed on touch . ExaminaHRCT of the temporal bone revealed a soft tissue density in the lateral one-third of the external auditory canal eroding the posterior wall and extending into the mastoid bone impinging on the sigmoid sinus plate . MRI with Gadolinium contrast of the temporal bone revealed a well-defined lobulated T2W hyperintense lesion  with parThe patient underwent left mastoid exploration under general anaesthesia. Postauricular incision with exposure of the mastoid cortex showed a well-defined sac with keratin debris in the mastoid which was originating from the bony cartilagenous region of the external auditory canal and eroding the mastoid cortex . The sigmoid sinus plate, mastoid antrum, dural plate and tympanic membrane were intact. The sac was removed in toto and sent for histopathological examination. The defect in the posterior external auditory canal was reconstructed with cartilage, temporalis fascia and periosteum.Histopathological examination showed the presence of keratin flakes and lamellated keratin and eroded fragments of bone along with fibro-collagenous stroma. Keratinized stratified squamous epithelium overlying fibro-collagenous stroma was infiltrated with lymphoplasmacytic infiltrate, cystic macrophages and multinucleated giant cells consistent with features of cholesteatoma .Follow-up after three months showed a well-delineated external auditory canal. Post-operative HRCT temporal bone at three months showed a well-healed cartilage graft surrounded by soft tissue without any evidence of residual disease.Cholesteatoma has been described as a sac of epithelium containing desquamated keratin debris with a propensity to erode surrounding bone . PresencEACC can be of 2 variants: primary and secondary. Primary EACC can be caused by first branchial cleft rudiment which creates a fistulous sinus and epithelium mass remnants in the fistulous sinus. It can also be caused by recurrent microtrauma or microangiopathy produced by cigarette smoking. Secondary EACC is either caused by obstruction or bony defects. Obstruction can be due to exostosis, nevi, stenosis or mycetomas. Bony defects can be post-inflammatory, post-traumatic, postoperative, radiogenic and post tumours. Sweeney et al suggested that vascular strip inversion during tympanoplasty surgery resulted in the formation of cholesteatoma. It can be a result of a shortened vascular strip, overthinning of the mastoid cortex and the influence of pressure negativity within the mastoid cavity ,5. CroniOtorrhea is the most common presentation followed by itching and fullness in the ear. On examination, the presence of keratin debris with a sac in the floor of the external auditory canal is the most common finding whereas, secondary EACC is commonly multifocal in nature. The presence of past history of surgery, repeated cotton-tipped applicator use, smoking and hearing aid use have to be determined to indicate the presence of predisposing factors for EACC. Our patient had a peculiar presentation of decreased hearing of short duration and examination revealed a smooth skin covered bulge in the posterior wall of the external auditory canal with the absence of keratin debris -4. HowevHRCT of the temporal bone is useful in diagnosis. It detects the presence of soft tissue density with bone erosion ,4. MRI wHolt proposed a 3 stage classification based on the extension of the sac from the external auditory canal to the mastoid . Naim etRecurrence following surgical treatment for vascular strip cholesteatoma is extremely rare -3. ThereProper placement of the vascular strip with the skin lining the external auditory canal with approximation of the incision margins is essential to prevent iatrogenic cholesteatoma formation. Close follow-up is essential to prevent any recurrence and diffusion weighted MRI plays a vital role in detection of recurrence.


To evaluate the influence of seasonal variation on in vitro fertilization (IVF) outcome in a large cohort population.A total of 5,765 IVF cycles conducted in Sheba medical center between 2013 and 2016 were retrospectively analyzed. The treatment cycles included 4214 ovarian stimulation and ovum pick up (OPU) cycles of which 3020 resulted in fresh embryo transfer and 1551 vitrified- warmed cycles of which1400 resulted in warmed embryo transfer. Cycles were assigned to seasons according to the date of OPU for fresh embryo transfer cycles or according to the date of embryo warming for vitrified warmed embryo transfer cycles.There were no statistically significant differences between the calendar months or seasons concerning the number of oocytes retrieved or fertilization rate in the fresh cycles. Throughout the 4 years of the study, the monthly clinical pregnancy rate fluctuated between 18.2% and 27.9% per fresh embryo transfer (mean 23.3%) and between 17.7% and 29.4% per vitrified warmed embryo transfer (mean 23%). These fluctuations did not follow any specific seasonal pattern.Our study did not demonstrate any significant influence of the calendar months or seasons on the clinical pregnancy rates of fresh or vitrified warmed embryo transfers. It might be speculated that the complete pharmaceutical control of the ovarian and endometrial function, as well as the homogeneous treatments, procedures and laboratory equipment used during the study period have lowered the influence of seasonal effect on IVF treatment outcome. Several epidemiologic studies throughout the world have demonstrated seasonal changes in natural conception and birth rate 2]. The . The 2].Data regarding the seasonal variation during assisted reproductive treatment is controversial. In in vitro fertilization (IVF), fluctuation in endogenous gonadotropins secretion is irrelevant due to the GnRH-analogues induced pituitary suppression, as part of controlled ovarian hyperstimulation (COH). Nonetheless, seasonal conditions may still influence the fertilization rate or embryo quality, as was suggested by Rojansky et al 8). They demonstrated a significant seasonal variability, with the highest fertilization rate and best quality embryos during the spring and the lowest in the autumn, correlated with the absolute number of light hours . They de. VanderkThe aforementioned inconsistency of associations between seasonality and IVF treatment outcome may derive from differences in the inclusion criteria, treatment protocols, laboratory equipment or geographical area. However, it may also derive from different seasonality effects on the multiple factors consisting the female reproductive tract. Because the hypothalamic- pituitary function is suppressed in assisted reproductive treatment, the seasonal effect is expressed as the end organ function, which is translated to fertilization rate and endometrial receptivity. A separate investigation of fresh or vitrified warmed embryo transfer cycles might isolate the seasonal effect on endometrial receptivity and its influence on IVF outcome.Prompted by these observations we aimed to investigate the influence of seasonal variation on IVF outcome in a tertiary, university-affiliated medical center, with stratification to fresh and vitrified warmed embryo transfer cycles.All consecutive patients undergoing assisted reproduction cycles resulting in ovum pick up (OPU) or vitrified warmed embryo transfer cycles, between January 2013 and December 2016, were included in the study analysis. The selection COH protocol or the type of endometrial preparation used, were the decision of the treating physician and largely dependent on the fashion at the time. The protocols of ovarian stimulation follow up and oocyte retrieval have been described elsewhere . In the Ethics statement: The study was approved by the Institutional Research Ethics Board of Sheba Medical Center (SMC 4850–18). Data collection was conducted anonymously and informed consent was not required.Data regarding the number of OPU procedures, vitrified warmed cycles, embryo transfers and pregnancy rate was prospectively collected. Outcome was assessed in terms of number of eggs retrieved per OPU cycle, rate of fertilization, positive beta-human chorionic gonadotropin test rate, clinical pregnancy rate and miscarriage rate. The clinical pregnancy rate was defined as the proportion of patients with one or more intrauterine gestational sacs demonstrated by transvaginal ultrasound 4 weeks after embryo transfer. In order to differentiate the impact of seasonal variation on endometrial receptivity from that of ovum and embryo quality, the clinical pregnancy rate was calculated separately for the fresh embryo transfer cycles and for the vitrified warmed embryo cycles. Results were compared between individual calendar months each year. The months were grouped to seasons which were defined before the analysis of data according to the calendar definition of seasons for Israel, each season lasting 3 months: spring: March-May, summer: June- August, fall: September- November, winter: December- February.The attribution of the patients to the corresponding seasons was made according to the date of the OPU for fresh embryo transfer cycles or according to the date of embryo warming for vitrified warmed embryo cycles.SPSS version 24 was used for statistical analysis. Monthly rate and means were calculated for the different variables. The effect of seasons and calendar months on cycle outcomes was examined using one way ANOVA for normally distributed variables and Kruskal-Wallis test for non-normally distributed variables. Two way ANOVA was conducted to examine the effect of interaction between season and cycle type (fresh or thawed) on the rate of clinical pregnancies.Between January 2013 and December 2016, 5765 assisted reproduction treatment cycles were performed in the IVF unit in Sheba medical center and were included in the analysis. The treatment cycles included 4214 ovarian stimulation and ovum pick up (OPU) cycles of which 3020 resulted in fresh embryo transfer and 1551 vitrified- warmed cycles of which1400 resulted in warmed embryo transfer. The overall clinical pregnancy rate during the study period was 23.3% for fresh embryo transfer cycles and 23% for vitrified warmed cycles (p = 0.74). Monthly and seasonal analysis of the fresh embryo transfer cycles did not demonstrate any significant differences regarding patients' age or COH variables. The mean number of oocytes retrieved per OPU, fertilization rate, mean number of embryos transferred and the clinical pregnancy rates per embryo transfer did not significantly differ between the seasons .Likewise, a separate analysis of the vitrified warmed cycles did not show any significant differences in the monthly or seasonal pregnancy rates . Two-waySeveral studies from different parts of the world that examined seasonal fluctuations in IVF treatment outcomes have yielded conflicting results. Moreover, even in studies that found seasonal effect on IVF treatment outcome, the results were not uniform regarding to which season yields optimal pregnancy rates. Stolwijk et al, in their Dutch study, found improved pregnancy rate during the period from November to February . On the In the present study, we could not demonstrate any significant seasonal influence on the IVF treatment outcome. In the fresh cycles, our results showed no significant seasonal difference in the number of retrieved ovum, fertilization rate or pregnancy rate. Likewise, there was no significant difference in the endometrial receptivity between the seasons, demonstrated by the similar pregnancy rates in the vitrified warmed cycles. This lack of seasonal influence, was also demonstrated in previous studies ,12,14. UThe lack of seasonal influence may be explained by the absolute control of the hypothalamic-pituitary-ovarian function and endometrial receptivity in IVF treatment cycles, making the environmental effects irrelevant. Likewise, seasonal changes in sperm quality are cancelled in IVF due to the use of intracytoplasmic sperm injection procedures.A limitation of our study is the missing data regarding the patients' characteristics such as number of treatment cycles and etiology of infertility. Likewise, our data does not include the quality grading of the transferred embryos or the day of transfer. Nonetheless, our practice is to transfer day 2–3 top quality embryo and the prevalence of patients that undergo embryo transfer without a top quality grading is less than 10% of transfers. An advantage of our study is the large sample size throughout four years period in a single center and the separate analysis of fresh and vitrified warmed cycles that isolates the endothelial receptivity factor.In conclusion, our study did not show any significant influence of the calendar months or seasons on the clinical pregnancy rates of fresh or vitrified warmed embryo transfers. It is possible that the complete pharmaceutical control of the ovarian and endometrial function as well as the homogeneous treatment, procedures and laboratory equipment during the study period minimize the influence of seasonal effect on fertilization treatment.S1 File(XLSX)Click here for additional data file.


This study was performed to determine whether metal block augmentation is suitable for large uncontained bone defect via evaluations of differences in biomechanical characteristics among the configurations of metal block augmentations for medium or large uncontained bone defects in revision total knee arthroplasty (TKA). Three-dimensional finite element (FE) models of the proximal tibia with revision TKA were developed and analyzed considering the configurations of the metal block augmentations for medium and large uncontained bone defects. To identify differences in biomechanical characteristics according to the configurations of metal block augmentations, the stress transfer, strain distribution, and peak von Mises stresses (PVMSs) were assessed. Large and medium uncontained bone defects had similar ranges of strain below the critical bone-damage strain for the metal block augmentations, but the strain distribution characteristics differed in response to the metal block-augmentation configurations. PVMSs exceeding the yield strength of the bone cement for the single metal block-augmentation configurations were, on average, 1.4 times higher than those for double metal block-augmentation configurations for both medium and large uncontained bone defects. These findings suggest that metal block augmentation may be suitable for large uncontained bone defects (≤20 mm), compared with the results obtained for metal block augmentation used in medium uncontained bone defects (≤10 mm). If possible, double metal block augmentation is recommended for both medium and large uncontained bone defects rather than single metal block augmentation. It is also recommended that the metal block augmentation should be customized to meet the contact characteristics with the cortical bone, thereby ensuring better stress transfer and reducing the risk of the bone resorption due to stress shielding and bone-cement failure. With the development of new biomaterials, as well as surgical techniques, total knee arthroplasty (TKA) has become a favored method to enhance patient quality of life. However, failures of TKA have been reported . Dalury During revision TKA, reconstruction of uncontained bone defects is frequently required because the failure of TKA is often associated with loss of bone from either the proximal aspect of the tibia or the distal aspect of the femur ,7. MetalThe main aims of the present study were to determine whether metal block augmentation was suitable for large uncontained bone defects by comparison with medium uncontained bone defects from a biomechanical view point, and to identify any differences in biomechanical characteristics among the configurations of metal block augmentation  for medium or large uncontained bone defects.A three-dimensional (3D) computer-aided design (CAD) model of the tibia was developed based on a composite tibia model . Resection of the tibia model was performed for revision TKA with metal block augmentation according to the traditional surgical procedure . Here, rPosterior-substituting (PS) fixed-bearing-type revision and metal block augmentation TKA  were used in the present study . Here, tThe insertion of the revision TKA components and the metal block augmentations into the tibia was performed following the traditional revision-TKA surgical guidelines, particularly the mechanical alignment strategy. The tibia baseplate component was placed in such a way that there was no protrusion over the cortical rim of the resected surface of the proximal tibia. The rotational alignment of the baseplate of the tibia component was then performed using the medial third of the tibia tuberosity landmark technique . The lonwww.Orthoload.com)  generated frequently during activities of daily living (ADLs) were considered based on the public database reported by Orthoload (oad.com)  22]. Th. Thwww.Ooad.com) . The suroad.com)  [25,26,2n = 6). Here, resection of the composite tibia for revision TKA, as well as insertion and alignment of the revision-TKA components, were performed following the same procedure used for FE model development. The composite tibiae with revision TKA and the femoral component were mounted onto the customized jig attached to the universal testing machine. The customized jig was designed specifically to represent knee flexion angle in the range of 0° to 140° considering the rollback phenomenon [Actual mechanical tests based on the ASTM F1800 standard were performed to validate the FE model using a universal testing machine  . The comenomenon . Eight henomenon . FE analThe principal stress flow inside the tibia was analyzed to characterize stress transfer in the tibia during motions associated with ADLs based on the metal block-augmentation configurations (types A–D). The distribution of strain on the resected surface of the cortical bone of the proximal tibia immediately below the metal block augmentation was characterized to predict the possibility of tibia bone resorption. The possibility of bone resorption related to radiolucent line was then analyzed by comparing the critical bone-damage strain (≤200 µstrain), which is capable of reducing the capacity for bone remodeling, leading to bone degeneration based on Frost’s mechanostat theory . Here, fThe strains computed from FE analyses and measured in mechanical tests are shown in The maximum and minimum principal stress flows within the cortical bone of the tibia are shown for revision TKAs with metal block augmentations applied for medium and large uncontained bone defects (types A–D) . The dirThe strain distributions on the resected surface of the cortical bone of the proximal tibia are shown for revision TKAs with metal block augmentations for medium and large uncontained bone defects (types A–D) . The maxThe distributions of von Mises stresses within the bone cements for types A–D are shown in The FE model used in this study showed a high degree of accuracy (93.8% ± 2.1%), although it had somewhat lower accuracy (85.8%–90.1%) in the anterior, anterior-medial, anterior-lateral, and posterior-lateral regions of the proximal tibia. This low accuracy was likely caused by differences between the material properties input into the FE model of the elastic element and the composite material actually used in the mechanical test and/or to erroneous attachment of strain sensors due to the morphological specificity of the posterior region of the proximal tibia. However, despite the differences between the results of FE analysis and actual mechanical tests, the accuracy of >85% for the FE models developed in this study suggested their high validity.The flow of maximum and minimum principal stresses of the tibia was generally similar in the proximal and distal regions for revision TKAs with metal block augmentations for both medium and large uncontained bone defects (types A–D). In four different metal block augmentations used for revision TKA, the maximum principal stress flowed from the proximal medial to the distal lateral direction, and the minimum principal stress flowed from the proximal medial to the lateral direction. This was considered characteristic of the tibia bending moment caused by the load applied to the medial and lateral condyle of the tibia. However, there were differences in magnitudes of maximum and minimum principal stresses according to the size of the bone defect. These differences were thought to be caused by the effect of stress shielding due to the differences in thickness of metal block augmentations. The metal block augmentation acted as a barrier, impeding the flow of principal stress of the proximal tibia; when the bone defect was large, both the thickness of the metal block augmentation and the effect of stress shielding increased. These results were consistent with those reported previously by Martinet et al.  and DeenThe range of strains below the critical bone-damage strain in metal block augmentations for large uncontained bone defects (types B and D) was similar to that for medium uncontained bone defects (types A and C), but the strain distribution characteristics were different in relation to the metal block-augmentation configurations. These differences in strain distribution may have been due to the characteristics of contact between the metal block augmentation and the resected surface of the cortical bone of the proximal tibia. The metal block augmentations for medium and large uncontained bone defects partially and completely covered the cortical bone of the proximal tibia, respectively. However, the contact characteristics did not cause significant differences in the range of strain below the critical bone-damage strain under the physiological loads considered in the present study. In conclusion, although diverse biological and mechanical factors influence bone resorption , metal bThe PVMS results within the bone cement suggested the likelihood of bone-cement failure. PVMSs exceeding the yield strength of the bone cement for single metal block-augmentation configurations (types C and D) were, on average, 1.4 times higher than those for double metal block-augmentation configurations (types A and B) for both medium and large uncontained bone defects. These observations suggested that the stress flow characteristics responded to differences in configuration (single or double) of the metal block augmentation. That is, the stresses generally flowed from the metal block to the bone cement directly in the case of single metal block augmentation, unlike double metal block augmentation. PVMSs exceeding the yield strength of the bone cement were generally detected in the posterior region of the last layer of the bone cement for large metal block augmentation and in the posterior-medial region of the last layer of bone cement for medium metal block augmentation. These observations were likely due to the characteristics of contact between the metal block augmentation and the cortical bone. Large metal block augmentation showed incomplete coverage in the posterior region of the resected surface of the proximal tibia. For medium metal block augmentation, there was an area of incomplete coverage in the posterior-medial region of the resected surface of the proximal region. In the case of a large bone defect, there was an area of incomplete coverage in the posterior region. These contact characteristics may have been important factors in increasing stress. These findings suggest that the number of metal blocks for metal augmentation configuration and the contact characteristics between the metal block and the cortical bone are important biomechanical factors related to bone-cement failure. Bone-cement failure generates bone cement debris, thus resulting in inflammation and osteolysis (bone resorption) in the tibia . In concIn conclusion, metal block augmentations may be suitable for large uncontained bone defects (10–20 mm) based on the results obtained with metal block augmentation for medium uncontained bone defects (≤10 mm), and the double metal block-augmentation configuration is recommended for both medium and large uncontained bone defects rather than single metal block augmentation, if possible. Metal block augmentation should be customized to achieve full contact with the cortical bone to ensure better stress transfer and thus reduce the risk of bone resorption by stress shielding and bone-cement failure. This study had several limitations. We did not consider the clinical factors affecting the results of the present study, including incomplete analysis of the likelihood of bone resorption (osteolysis) based on a single value (criterion) despite the influence of diverse biological and mechanical factors; nor did we evaluate clinical efficacy due to difficulty in performing longitudinal follow-up evaluations of patients within a short period. Further studies are required to address these limitations. Nevertheless, the results of the present study are useful for identifying the biomechanical characteristics associated with successful outcomes of revision TKA with metal block augmentation for medium and large uncontained bone defects.


In this report, a blue anti-transmission film (BATF) has been introduced to improve the color-conversion efficiency (CCE) and the stability of quantum dot (QD) films. The results indicate that the CCE can be increased by as much as 93% using 15 layers of BATFs under the same QD concentration. Therefore, the same CCE can be achieved using BATF-QD hybrid films with a lower QD concentration when compared with standard QD films. The hybrid and QD films with the same CCE of 60% were aged at an environmental temperature of 25°C and with a 10 mA injection current light-emitting diode source. The CCE and luminous efficacy that are gained by the hybrid film increased by 42.8% and 24.5%, respectively, when compared with that gained by the QD film after aging for the same time period of approximately 65 h. In addition, the hybrid film can effectively suppress the red-shift phenomenon of the QD light spectra, as well as an expansion of the full-width at half maximum. Consequently, these BATF-QD hybrid films with excellent optical performance and stability show great potential for illumination and display applications. Quantum dots (QDs) have several advantages for lighting applications, including high quantum yield, high color purity, and easy manufacture. They have demonstrated great potential in optoelectronic devices, such as light-emitting diodes . Blue LEThe color-conversion efficiency (CCE) refers to the proportion of QD light radiant power to the total radiant power. It determines the output color coordinates of LEDs ,18. ThisIn this study, a blue anti-transmission film (BATF) is introduced in order to improve the CCE and stability of QD films. The absorption of QD films and BATF-QD hybrid films were investigated. Then, the influence of the BATF-QD hybrid films on the optical performance of LEDs was investigated. Finally, the optical performance and working stability of the BATF-QD hybrid films were compared with QD films under the same CCE.The QDs with the CdSe/ZnS core/shell structure  were used in this study. The emission and absorption properties of these QDs in chloroform solution are shown in The working stability was investigated according to the aging tests at an environmental temperature of 25 °C without heat sink for thermal managements . The BATThe optical properties including wavelength-dependent transmittance, reflection, and absorption of the commercial BATF were characterized, as shown in The QD film and BATF-QD hybrid film with different layers of BATFs and different concentrations of QDs were applied to a blue LED source. The radiant power, including the total radiant power, radiant power of chip light, and radiant power of QD light, of these QD-based LEDs is given in Their luminous efficacy and CCE are given in Moreover, it is interesting that LEDs using BATF-QD hybrid films with a lower QD concentration can attain the same CCE as QD films with larger QD concentrations. To further investigate this issue, the results for the QD concentration for the same CCE when a different number of BATF layers were used, are given in The aging test was performed to evaluate this issue, the optical performances of LEDs using hybrid films  and QD films  with different aging time are shown in The spectra of LEDs using QD films and BATF-QD hybrid films with different QD concentrations and BATF layers are further investigated, as given in In this report, BATF was introduced to improve the CCE and stability of QD films. The results show that the BATF-QD hybrid films significantly increase the CCE by 93% using 15 layers of BATFs with the same QD concentration. This is caused by the stronger absorption and reflection of chip light. The same CCE (as high as 60%) can be achieved using hybrid films with a QD concentration half that of QD films, although the initial luminous efficacy (before aging) acquired by the hybrid film was substantially lower than that acquired by the QD film with the same CCE of 60%. After aging for approximately 65 h, the CCE and luminous efficacy gained by the hybrid film increased by 42.8% and 24.5% when compared with that of the QD film. These results demonstrate that a hybrid film with a lower QD concentration can significantly decrease conversion losses due to the reduced probability of reabsorption events. As a result, the stability and optical performance are significantly increased after aging. Because of the lower QD concentration usage, the hybrid film can also effectively suppress the red-shift phenomenon of the spectra, which simultaneously leads to a smaller FWHM of the QD light. Therefore, the BATF-QD hybrid films show great potential in the illumination and display applications.In future investigations, we intend to optimize the BATF structure to decrease its absorption while increasing its reflection. We believe that this will further improve the light extraction of LEDs by avoiding the absorption losses introduce by the BATFs.


Triplane fractures of the proximal tibia are less well known than the distal extremity. The diagnosis is based on a good analysis of X-rays and possibly CT images to better plan the management. The authors reports a triplane fracture of the proximal tibial in a 12 year old boy treated by closed reduction and internal fixation. To our knowledge, only a dozen cases have been reported in the literature with generally a good evolution of the fracture. Triplane fracture of the proximal tibia occurs in three planes  and it typically occurs in adolescence and crosses through the articular surface, the epiphysis, the physis and the metaphysis. Triplane fractures are known in the distal part of the tibia and were first described by Lynn in 1972 . DiagnosA 12-year-old boy with an overweight, consulted the emergency department after a closed trauma of the right knee following a fall from its own height. On examination, he has a painful and swollen knee with limited motion and there was no neurovascular abnormality. The antero-posterior radiograph revealed a fracture through the medial physis extending through the epiphysis classified Salter-Harris III . HoweverAlthough the fractures of the epiphyseal cartilage injuries are common in the childhood, epiphyseal fractures involving the proximal tibia entities are very rare and account for 1 to 3% of all physeal injuries , 7. SaltProximal tibial triplane fractures are rare injuries but carry with them the need for clinical vigilance. These fractures are high energy injuries that can result in multiple intra-articular and physeal fragments that require individual anatomic reduction and stabilization in order to prevent future arthritis, pain, and deformity. Because of the involvement of the physeal growth plate, long-term radiographic follow-up of the affected extremity is necessary to treat any angular deformity or leg length difference that might occur.The authors declare no competing interests.


It implies the evaluation of the organism response to the biomaterial implantation. Low-molecular degradation products, the chito-oligomers, are resulting mainly from the influence of enzymes, which are found in the organism fluids. Within this study, we have performed the computational assessment of pharmacological profiles and toxicological effects on human health of small chito-oligomers with distinct molecular weights, deacetylation degrees, and acetylation patterns. Our approach is based on the fact that regulatory agencies and researchers in the drug development field rely on the use of modeling to predict biological effects and to guide decision making. To be considered as valid for regulatory purposes, every model that is used for predictions should be associated with a defined toxicological endpoint and has appropriate robustness and predictivity. Within this context, we have used FAF-Drugs4, SwissADME, and PreADMET tools to predict the oral bioavailability of chito-oligomers and SwissADME, PreADMET, and admetSAR2.0 tools to predict their pharmacokinetic profiles. The organs and genomic toxicities have been assessed using admetSAR2.0 and PreADMET tools but specific computational facilities have been also used for predicting different toxicological endpoints: Pred-Skin for skin sensitization, CarcinoPred-EL for carcinogenicity, Pred-hERG for cardiotoxicity, ENDOCRINE DISRUPTOME for endocrine disruption potential and Toxtree for carcinogenicity and mutagenicity. Our computational assessment showed that investigated chito-oligomers reflect promising pharmacological profiles and limited toxicological effects on humans, regardless of molecular weight, deacetylation degree, and acetylation pattern. According to our results, there is a possible inhibition of the organic anion transporting peptides OATP1B1 and/or OATP1B3, a weak potential of cardiotoxicity, a minor probability of affecting the androgen receptor, and phospholipidosis. Consequently, these results may be used to guide or to complement the existing  Chitin is a polysaccharide abundantly found in nature, especially in crustaceans, but also in insects and fungi. Chitosan is obtained from chitin by chemical or enzymatic deacetylation Rinaudo, . The difThere are many different ways in which humans have exposure to chito-oligomers (COs): by the degradation of implanted materials based on chitosan, the use of pharmaceutical products containing COs and/or occupational exposure. The low-molecular degradation products of chitosan, the chito-oligomers, occur as a result of the influence of enzymes which are present in bodily fluids  homo-chito-oligosaccharides containing only GlcN or GlcNAc units and (ii) hetero-chito-oligosaccharides, containing both GlcN and GlcNAc with varying degrees of deacetylation  and a varying position of glucosamine residues in the oligomer chain . GlcN unit carries an amino group that is protonated at physiological pH  tools. Safe production considers the use of environmentally friendly technologies and the potential risk for professionals involved in R&D and industrial processes. Safe use and waste management reflect safe handling  of products and wastes. Safety profiles of COs should depend on their structure and physicochemical properties  must be considered when producing and using chitosan and its oligomers. Safe-by-design is a relatively new concept planned to be used in the research and development (R&D) field and industry, and include safe design, safe production, safe use and waste management for new materials and technologies  prediction of the pharmacological profiles and toxicological endpoints  of COs containing up to 8 monomeric units (water soluble chito-oligomers) and (2) assessment of the influence of the MW, DDA, and AP on the toxicological and pharmacological profiles of investigated COs by using computational approaches.Among the numerous available computational tools for predicting the pharmacological properties and toxicological effects of chemical compounds on human health, we have selected those with an accuracy of a prediction usually higher than 70% and with friendly interfaces and tutorials that are available for free (online or open-source). The chito-oligomers that we have considered in this study are presented in https://chemicalize.com). This software also generates structural files in mol format to be used for further predictions We have obtained 3D sdf files using OpenBabel  formulas of the considered COs are built using ACD/ChemSketch software  molecular descriptors calculation; (ii) drug likeness prediction considering well known rules; (iii) ADME prediction; and (iv) toxicity prediction [mutagenicity by Ames test and rodent carcinogenicity;  utility has been used for accomplishing predictions concerning the carcinogenicity of investigated chemicals  and a multiclass prediction  along with the probability of the prediction for each class. The predictions have an accuracy of up to 89%  KEndocrine disruption potential is evaluated using ENDOCRINE DISRUPTOME computational tool . The outcomes are presented in With the exceptions of the monomeric and some of the dimeric chito-oligomers, the outcomes of FAF-Drugs4 indicate the lack of oral bioavailability of the other investigated COs because of their molecular weight and extensive hydrogen bonding potential. Similar results concerning the lack of human oral bioavailability of investigated COs containing more than 2 monomeric units have been obtained using admetSAR2.0 , PreADMEAs expected, the oral bioavailability decreases with increasing molecular weight and increases with the deacetylation degree. PreADMET predictions concerning the percent of the human intestinal absorption HIA,  reveal aPredictions concerning the distribution  of the investigated COs have been obtained using admetSAR2.0 tool and the outcomes are illustrated in Data presented in SwissADME, PreADMET, and admetSAR2.0 tools have been also used to assess the metabolism of COs by predicting the probability for every compound to be a substrate or to inhibit the human cytochromes P450 (CYP) involved in the metabolism of xenobiotics. The outcomes of SwissADME and admetSAR2.0 tools indicate that COs considered in this study are not substrates and inhibitors of CYPs , 4. The Predictions concerning the probability of the inhibition of the organic anion and cation transporter peptides by the investigated COs are also obtained using admetSAR2.0 tool and are illustrated in Predictions concerning the organ  and genomic toxicity of investigated COs obtained using admetSAR2.0 and PreADMET tools are revealed in None of the investigated oligomers have carcinogenic potential, does not produce eye irritations and corrosion. Excepting the monomeric and dimeric units that are not predicted to block the hERG, the other oligomers reveal moderate potentials of hERG channel blocking. Totally acetylated oligomers and small oligomers containing deacetylated units are predicted by the PreADMET tool as displaying mutagenic potential. Besides admetSAR2.0 and PreADMET tools, carcinogenicity and mutagenicity of investigated COs have also been assessed using CarcinoPred-EL and Toxtree and their outcomes displayed no carcinogenicity and no Ames toxicity for every considered oligomer . The conFor assessing cardiotoxicity of investigated COs we have also considered Pred-hERG prediction tool and the results are presented in Predictions made using the binary model illustrate that, except GlcN and GlcNAc monomers, that are considered as non-hERG K+ blockers, the other investigated COs are predicted as having hERG K+ blocking potential but the probabilities of these predictions are relatively small. Predictions based on the multiclass models reveal non-hERG blocking potential for all investigated COs, also with relatively small probabilities. Predictions reliability reported using Pred-hERG are ranging between 83 and 84% for the binary model and between 66 and 79% for the multiclass models  are capable to act as AR antagonists  are not consistent between the computational tools that were used in this study. SwissADME tool predicts that all investigated COs are substrates of P-gp, but admetSAR2.0 illustrate the contrary. PreADMET tool reveals that investigated COs are not inhibitors of P-glycoprotein, but admetSAR2.0 displays that oligomers containing at least 4 monomeric units are potential inhibitors of P-glycoprotein. It illustrates that the activity of P-glycoprotein may be affected by the presence of COs and absorption and retention of COs in the cells could be impaired. This aspect must be further considered in experimental studies. Investigated COs reveal no potential to penetrate the blood brain barrier and it underlines their minimal side effects against the central nervous system. An Investigated COs reveal no toxicity, but partially and totally deacetylated chitin oligomers are predicted to produce phospholipidosis, a disorder characterized by the accumulation in excess of phospholipids in tissues. This prediction is not unexpected as chitosan is a cationic polymer and it is known that cationic amphiphilic drugs may produce phospholipidosis  are able to inhibit organic anion polypeptide transporters OATP1B1, OATP1B3, and OATP2B1. OATP1B1 and OATP1B3 are exclusively expressed in the liver, this organ being responsible for the hepatic uptake of some drugs, bile acids and some endogenous compounds. OATP2B1 is found in the liver and other tissues being associated with the oral absorption of chemicals. The inhibition of these transporters conducts to clinically relevant drug-drug interactions and to modified pharmacological effects and adverse reactions of drugs Maeda, . AnotherThe outcomes of both admetSAR2.0 and Pred-hERG revealed that investigated COs, excepting the monomers, illustrate moderate potentials of hERG channel blocking. The hERG blockage potential of investigated COs increases with the molecular weight and it slightly depends on the acetylation degree and pattern. Literature data reveal the cavity of the hERG pore is large and is able to accommodate compounds with very high molecular weight  the models used for predictions could not be adequate as the data regarding the biological activities of well-defined COs are limited and these data are not considered when building the models used for predictions; (ii) these predictions do not take into account the quantity of COs and the basic variables of experimental studies ; (iii) there are difficulties concerning the modeling of the toxicological endpoint because the lack of a complete understanding of its biology and of the complexity of processes involved. These lacunas may affect the experimental validations as data that were used for model building may originate from various experimental approaches that are different from those used for validation, as it is recognized that inconsistencies between predictions and experiments can often be attributed to the fact that they do not test the same assumptions  reflect a weak disruption potential against AR and GR; (v) totally deacetylated oligomers are considered to produce phospholipidosis.As possible harmful effects we have noticed the followings: (i) all investigated COs revealed high potential of inhibition of the OATP1B3 and COs containing only deacetylated units also reflect inhibition potential of the OATP1B1; (ii) COs containing more than 2 units reflect a moderate potential of cardiotoxicity; (iii) some of considered COs reflect small probabilities to produce hepatotoxicity; (iv) smaller oligomers (Predictions concerning the interactions of investigated COs with P-glycoprotein and CYPs are unclear and they must be further considered in experimental studies.We have also examined the influence of the molecular weight, deacetylation degree, and pattern on the pharmacological profiles and toxicological endpoints of investigated COs. The oral bioavailability of investigated COs decreases with increasing MW and deacetylation degree. Taking into account that bioavailability profile could be the main factor limiting the efficiency of a drug, this information is of interest. There is a slightly dependence of hepatotoxicity and cardiotoxicity on the molecular weight and on the deacetylation degree and pattern of COs. The cardiotoxicity of investigated COs increases poorly with the molecular weight, decreases slightly with the deacetylation degree and is not influenced by deacetylation pattern. Hepatotoxicity increases with the molecular weight, decrease with the deacetylation degree and depends on the deacetylation pattern.All datasets generated for this study are included in the manuscript/DR performed the computations using FAF-Drugs, admetSAR, PreADMET, Pred-Skin, and Endocrine Disruptome, to results analysis and contributed to manuscript editing. MR performed computations using, SwissADME, Pred-hERG, CarcinoPred-El, and Toxtree, to results analysis and contributed to manuscript editing. CS, MS, EH, PW, TC, and GP contributed to the analysis of results, conception, and design of the manuscript. VO furnished the SMILES and structural formulas of oligomers and contributed to the conception and design of the manuscript. AI conceived and planned the study and contributed to the conception and design of the manuscript. All authors contributed to revise the manuscript and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Domestic dogs have been central to life in the North American Arctic for millennia. The ancestors of the Inuit were the first to introduce the widespread usage of dog sledge transportation technology to the Americas, but whether the Inuit adopted local Palaeo-Inuit dogs or introduced a new dog population to the region remains unknown. To test these hypotheses, we generated mitochondrial DNA and geometric morphometric data of skull and dental elements from a total of 922 North American Arctic dogs and wolves spanning over 4500 years. Our analyses revealed that dogs from Inuit sites dating from 2000 BP possess morphological and genetic signatures that distinguish them from earlier Palaeo-Inuit dogs, and identified a novel mitochondrial clade in eastern Siberia and Alaska. The genetic legacy of these Inuit dogs survives today in modern Arctic sledge dogs despite phenotypic differences between archaeological and modern Arctic dogs. Together, our data reveal that Inuit dogs derive from a secondary pre-contact migration of dogs distinct from Palaeo-Inuit dogs, and probably aided the Inuit expansion across the North American Arctic beginning around 1000 BP. Early dog specimens from Late Pleistocene to Early Holocene sites throughout northeastern Asia [Dogs  analyses  to explo2.(a)To better understand the diversity of ancient Arctic dog morphologies, we investigated the phenotypic variation between Palaeo-Inuit, Inuit and more recent Greenland dog , as well as Arctic wolf populations. To do so, we used GMM on the crania, lower first molars and hemi-mandibles . In parta and figure 1c). Where the differences are significant, the mean cross-validation between Palaeo-Inuit and Inuit dogs ranges from 71.0% to 83.8% depending on the element . Inuit dogs exhibit a similar cranial shape to the recent Arctic dogs while differing from the Palaeo-Inuit dogs, though the Inuit dogs differ equivalently from both Palaeo-Inuit and recent Arctic dogs in their molar and mandible , two Palaeo-Inuit specimens from Alaska possessed A2a haplotypes  suggesting that the A2a haplotype was present in North American Arctic prior to the Inuit period . We founFST = 0.33, p < 0.001), but were similar between Siberian and North American Inuit samples . These results are consistent with the results of previous human genetic analyses which have linked Inuit groups to both Siberian and earlier Alaskan populations [Temporal shifts in mitochondrial haplotype frequencies suggest a near-replacement of Palaeo-Inuit dogs in the North American Arctic coinciding with the Inuit expansion from Siberia Dogs are an important cultural symbol in the North American Arctic where sledge dogs and dog traction are highly visible components of Arctic identity –35. DogsWhile most Arctic assemblages primarily consist of domestic canid specimens, there is evidence that wolves were also exploited during the Inuit period. On the basis of size, a large mandible from Nunalleq—a Thule Inuit site in southwestern Alaska —was provBoth nineteenth century Arctic explorers and twentieth century anthropologists reported that Arctic groups often encouraged hybridization of their dogs with wolf populations in order to maintain and strengthen their lineages –44. In t(c)Phylogenetic analysis also revealed seven canid mitogenomes  clustering with modern Eurasian wolves, outside any known domestic dog clades, forming a novel subclade referred to in this study as X clade . Three of the samples in X clade are derived from archaeological contexts: two from Neolithic Siberian canids excavated at the Boisman II site in Khasansky District of Primorsky Krai, Russia  and one dog from the Birnirk site, Pajpel'gak in Chukotka (03.P04.H1.1024). Additionally, this novel subclade contains four historical dogs from Kamchatka, Chukotka, Bering Island and Alaska. While the origins of the fur from the ethnographic Alaskan clothing (TRF.02.29) cannot be conclusively confirmed as dog based on the sample record alone, the ethnographic samples of aboriginal dogs collected from Kamchatka, Chukotka and Bering Island have a definitive classification, having been collected from dogs during the twentieth century .While the X-clade clusters with modern grey wolves, the inclusion of several recent dogs with known origin eliminates the possibility of this clade representing grey wolves. Although, as previously discussed, interbreeding between dogs and wolves is generally biased towards the mating of male wolves with female dogs which would not result in the passing of mitochondrial genomes from wolves to dogs. The X clade could represent an ancient introgression event of mitochondrial wolf haplotypes into dogs. Additionally, the ancient origin of the clade is demonstrated by sample AL2991 (BOIS 5), which was directly dated to between 6660 and 6495 cal. BP, falling within the clade. This ancient origin is corroborated by Bayesian tree, generated with BEAST2.4 and calibrated with dated samples, estimating the origin of the clade between 5300 and 10 000 years BP . Due to constraints on coverage used in the Bayesian analysis sample AL2991, the oldest dated sample in the clade, was not included in the analysis. The inclusion of AL2991 may have pushed the age of the clade backwards as AL2991 lies well within rather than basal to the clade and is a few millenia older than the samples included in the Bayesian analysis. Even AL2991 included in the Bayesian analysis the sample age falls within the estimated window of origin for the X clade. The comparatively recent origin of this clade, compared to some of the more prominent mitochondrial clades, suggests that the X clade was not present in dogs at the time of domestication. The X clade lineage also appears in historical dogs, demonstrating the continuation of the lineage until at least 75 years ago. The single individual carrying an X clade mitochondrial genome in Alaska may indicate a relatively recent introduction of the lineage to the North American Arctic after the arrival of the Inuit, explaining why the lineage did not spread across the North American Arctic during the Inuit migration and expansion like A1a and A1b haplotypes. The absence of the X-clade haplotypes in published studies speaks to the apparent low frequency and restricted distribution of these haplotypes to far eastern Siberia and Alaska. Furthermore, the absence of these haplotypes in modern dogs may reflect the lack of systematic sampling in the region to date, the low frequency or the disappearance of these haplotypes.3.The phenotypic and genetic data presented here suggest that a novel dog population that was morphologically divergent from, and genetically more diverse than earlier Palaeo-Inuit dogs, accompanied Inuit migrants into and across the North American Arctic. The Inuit migration represents a significant episode in the history of dogs in the North American Arctic, and the dispersal of Inuit culture is mirrored in the dispersal of its genetically distinct dogs. More specifically, our data indicate that though dogs that possessed A2a signatures were present in the North American Arctic prior to the arrival of the Inuit, they were responsible for dominance and eastward expansion of the A2a subclade. The settlement of the North American Arctic by Inuit cultures brought a more mitochondrially diverse and morphologically distinct dog population, and the subsequent European colonization of the North American Arctic further influenced the mitochondrial diversity in more recent centuries. Despite the fact that dog sledging is widely associated with the North American Arctic today, sledging was probably less common prior to the Inuit period. The preservation of these distinctive Inuit dogs is likely a reflection of the highly specialized role that dogs played in both long-range transportation and daily subsistence practices in Inuit society. The legacy of these Inuit dogs survives today in Arctic sledge dogs, making them some of the last remaining descendant populations of a pre-European dog lineage in the Americas.4.(a)Archaeological and ethnographic materials were sampled from Palaeo-Inuit, Inuit, historical and modern contexts across the North American Arctic, subarctic Eastern Canada, Iceland and eastern Siberia. A total genetic dataset of 628 specimens was composed of 186 novel sequences  and 221 (b)All samples were processed in facilities dedicated to ancient DNA analyses and all PCRs were performed in separate facilities . AncientTotal genomic DNA was extracted from 628 samples from across Russia and Arctic North America using modified DNA extraction methods from previous studies Geometric morphometric analyses were performed on a total of 571 elements (MNI = 401). Mandible and lower M1 shape were analysed in two-dimensional from photographs  digitized with 15 landmarks, and two landmarks and 49 sliding semilandmarks, respectively, using tpsDig2  . Crania Size variation was tested with Wilcoxon test and visualized with boxplots showing the log-transformed centroid size. Shape and form (size + shape) variation were explored with principal component analysis , before the differences were tested with MANOVA and visualized using canonical variate analyses  based on a reduced number of PCA scores . Differe


Howiesons Poort (HP) sites, over the past decades, have provided exceptional access to anthropogenic remains that are enhancing our understanding of early modern human behaviour during the Middle Stone Age in southern Africa. Here, we analyse the technological and typological trends in the lithic record that form part of these behaviours, based on the HP sequence recently excavated at Klipdrift Shelter, located on the southern Cape coast of South Africa. This study contributes to enhance knowledge on the mechanisms of changes that occurred during the transition to the post-HP. Despite patterns of continuity observed, notably for core reduction methods, the seven successive lithic assemblages show significant changes in the typological characteristics and raw material selection but also in the relative importance of blade production over time. However, these changes are not necessarily synchronic and occur either as gradual processes or as abrupt technological shifts. Consequently, we cross-examine the association between the lithic phasing and other anthropogenic remains within the HP sequence at Klipdrift Shelter. We explore the implications of these patterns of changes in terms of cultural behaviours and population dynamics during the HP and we highlight the relationship between the different phases of the HP sequence at Klipdrift Shelter and those from other South African HP sites. The Howiesons Poort (HP) is one of the most intensively discussed periods of the Late Pleistocene Middle Stone Age (MSA) in southern Africa. This is in part due to outstanding complex material culture, such as geometrically engraved ostrich eggshells and worked ochre pieces –7, foundThe HP is often considered as an exceptional and short-lived cultural unit within the MSA . . versus es , located on the southern Cape coast of South Africa  and explchaîne opératoire of blade production in layer PBD.KDS is the eastern most shelter of the Klipdrift Complex  located Our analysis is based on all of the HP layers, named (from the lowest level): PCA, PBE, PBD, PBC, PBA/PBB, PAZ, PAY. A total of 6,837 lithics were recorded individually, in addition to 4,837 chunks and pebbles which are not further discussed here. The chunks are mainly from quartzite and are potentially products of roof spalling see , while sWe use the term blade for all products that fit the size ratio of length ≥ 2 x width, regardless their maximal length, as it follows a unimodal distribution, as observed at Rose Cottage Cave . The blaDifferent categories of raw material are represented in the HP sequence of KDS for pieces >2cm, among which silcrete (29%), coarse quartzite (33%) and milky quartz (33%) are by far the most frequent when all the layers are considered together. However, important changes in their respective proportions occur through the sequence, reflecting significant changes in raw material selection over time .The milky quartz at KDS is highly homogeneous in structure. Quartz blades and cores with remnant cortex (3.4%) show either natural surfaces (plain angular or irregular) or pebble surfaces in similar proportions. Quartz is currently available in the direct vicinity of the shelter, on the beach beneath the site and in the Cape Supergroup sequence near the site. Crystal quartz (ie. transparent), represented in low proportions , derive Quartzite is mostly coarse and corresponds better to the quartzite type available in the shelter walls than to the fine grained quartzite cobbles available on the beach beneath the site. The rare coarse quartzite cores and blades bearing cortical surfaces (1.2%) confirm this observation since they show planar natural fractures rather than cobble waterworn cortex. Cobbles have been exclusively selected for blade production as all cores and blades are in fine quartzite, sometimes associated with remnant cobble cortex.koppies” (rocky hills) where silcrete outcrops occur within a 10 km radius around the site. The colour, textural and structural variations of the silcrete types present in the archaeological sample match the variations observed in the reference geological sample collected at several locations close to the site , only appears in the HP sequence from PAZ to PAY and is the exclusive motif of engraved OES in PAY. In layers PBC to PAZ, the sub-parallel rectilinear or curved lines motif would be the most common. Further analyses are needed to confirm the exclusivity of this design to the two upper layers, but it seem to accompany the general behavioral change towards the Post-HP. Interestingly, the extensive study of engraved OES at Diepkloof , 63 has The dynamic changes observed at KDS are unlikely caused by dramatic events such as population replacements. The overall similarities of the HP successions on a regional scale but also on the wider regional scale rule out the assumption that behavioural changes at KDS are solely driven by local innovations. Strong arguments in favour of interactions with other HP populations are even better supported by the occurrence of engraved ostrich eggshells both at KDS  and DiepWe regard the internal variability observed at KDS and at other HP sites within southern Africa as the expression of a highly inventive and dynamic culture, open to changes and driven by strong social interactions, especially at a regional scale. This leads to strong recurrences in the patterns of changes during the HP over large spatial scales. At KDS the changes in lithic strategies are generally not synchronous with changes in symbolic behaviours, subsistence behaviours or environmental conditions—with the exception of layer PBC. This opens avenues for discussion about the relevance of models of behavioural evolution during the HP based on single proxies. Layer PBC at KDS marks the most profound shift that sees the gradual introduction of components that are typical of the post-HP. The transition to the post-HP, and the effective termination of HP technologies, starts with the shift from the Intermediate to the Late HP well before the appearance of the typical post-HP unifacial points. This transitional process provides a marker for the disappearance of the HP from the southern African MSA.S1 TableBlanks: FL: Flake, BL: Blade, Indet.: Indeterminate.(DOCX)Click here for additional data file.


The DNA-protein interactions play vital roles in the central dogma of molecular biology. Proper interactions between DNA andprotein would lead to the onset of various biological phenomena like transcription, translation, and replication. However, themechanisms of these well-known processes vary between prokaryotic and eukaryotic organisms. The exact molecular mechanisms ofthese processes are unknown. Therefore, it is of interest to report the comparative estimate of the different properties of the DNAbinding proteins from prokaryotic and eukaryotic organisms. We analyzed the different sequence-based features such as the frequencyof amino acids and amino acid groups in the proteins of prokaryotes and eukaryotes by statistical measures. The general pattern ofdifferences between the various DNA binding proteins for the development of a prediction system to discriminate between theseproteins between prokaryotes and eukaryotes is documented. DNA protein interactions as in DNA transcription are at the heartof the central dogma of molecular biology. The transcription isthe process of transfer of genetic information from DNAmolecules. The process is regulated by a set of proteins. Theseproteins are referred to as the transcription factors (TFs) . ThemecHowever, the molecular details of the transcription processes inthe pro- and eukaryotic organisms are still at its infancy. In thiswork, we tried to analyze the different aspects of thetranscription factors from pro- and eukaryotic organisms. For thecomparison purposes, we used the amino acid sequences of theDNA binding proteins (DBPs) and transcription factors (TFs)from UniProt .We compared the TFs using their sequence information only assequence is more abundant than structure . The maiWe downloaded the sequences of DNA binding proteins (DBPs)from UniProt . We collThe raw dataset may be biased because of having multiple copiesof a single sequence. We, therefore, performed a redundancycheck, by means of distance matrix calculation. The distancematrix was generated by Hamming distance algorithm , 7.AfteAfter the preparation of these clean datasets, we performedamino acids and amino acids group frequency calculations. Wecategorized the amino acid groups into Hydrophobic (HB),Hydrophilic (HI), Charged (CR), Basic (BS) and Acidic (AC) .This frWe used the overall amino acid frequencies and amino acidsgroup frequencies of the prokaryotic and eukaryotic organisms asfeatures to distinguish between prokaryotic and eukaryoticorganisms using the tool WEKA . WEKA isA distinguishable difference was found in the frequency patternsbetween eukaryotic and prokaryotic amino acid sequences in theDNA binding proteins. This distinguishable difference pattern inamino acid and amino acid group frequency can be used todiscriminate them. The bar graph  and boxpWe found that amino acids and amino acid group frequency canbe used as features to train a SMO classifier in WEKA todistinguish prokaryotic and eukaryotic DNA binding proteins on the basis of their amino acid and amino acid group frequency as given in Data show that the sequence-based features of the DBPs and TFscould very well be used to distinguish between these classes oforganisms. In all our analyses, we obtained an overall accuracygreater than 85% and an AUC value of 0.9. However, we had touse a comparatively small dataset due to paucity of data in thedatabases. None-the-less, this is the up to date data available tillthe date mentioned in the manuscript. Available predictorscombine both the sequence and structural information for thediscrimination purposes. Our predictor uses only sequenceinformation and therefore may be considered a more general oneas sequence information is more abundant than structuralinformation. For extraction of the features, we used an in-housescript written in python.


Anguilla japonica) recruitment to Japan was very low during the early 2017−2018 recruitment season when most glass eels are usually caught, but catches increased in the late recruitment season when recruitment usually decreases. Concurrently, the Kuroshio meander south of Japan had formed again after the previous event ended in 2005. The role of the large meander and ocean circulation features such as the North Equatorial Current (NEC) in the unusual 2017−2018 Japanese eel recruitment timing-pattern was investigated using a three-dimensional particle tracking model that simulated swimming behaviors of virtual larvae (v-larvae) in addition to their drift in ocean currents. Four recruitment seasons were selected for when the Kuroshio large meander was present  or absent , and when NEC was shifted north  or south . The simulated recruitment timing-patterns were similar to the actual recent-year recruitment, with no early recruitment period v-larvae arrival to southern Japan and increased late period recruitment occurring. Rather than being related to the presence of the Kuroshio large meander, the late arrival appeared to be caused by a southward shifted, weak North Equatorial Current near the spawning area, a longer Subtropical Countercurrent eddy region retention time, and a weak Kuroshio during the early migration and recruitment period of those years. In the late recruitment period, the Kuroshio was stronger than other selected years near the East China Sea and south of Japan and v-larvae were transported more rapidly. The Kuroshio large meander may influence local eel recruitment in Japan, and the recirculation formed by the large meander could potentially enhance recruitment to the Tokai region. Oriented (northwestward) swimming v-larvae were less affected by the large meander, and showed higher recruitment success than those using along-current swimming. Although the Kuroshio large meander did not seem to be responsible for the unusual recruitment pattern in 2018, how Japanese eel larvae and glass eels actually cross out of the Kuroshio and reach coastal waters in Japan remains to be explored.Japanese eel ( Anguillid eels are widely distributed in the Indo-Pacific and North Atlantic regions where the juveniles live in freshwater and estuarine habitats , 2. TheiAnguilla japonica, is one of the most important eel species for fisheries and aquaculture, and it has been listed as endangered on the IUCN red list [The Japanese eel, red list . Among tred list , and recred list . The grored list , 21 in tred list , 23. Thered list , which mred list .https://goo.gl/JmU54s). Due to the lack of eel catches in the early recruitment season, the market transaction price of glass eels in Japan had reached a historical maximum of 30,000 USD per kilogram . The drastic decline of eel catches was a big news story that was covered by the media worldwide. During the same period, the Kuroshio large meander was occurring. The Kuroshio large meander forms when the path of the current flow turns sharply to the south and then turns back north in the region south of Japan [The glass eel recruitment season of the Japanese eel in East Asia is from November to May of the next year. The glass eel catches in Japan generally reach their maximum levels early in the recruitment season in December or January and decrease after that . In Deceof Japan . The Kurhttps://goo.gl/QTEp45).The Kuroshio meander path does not change the current path along the entire coast of Japan, but mainly influences the path near the Tokai region . The KurHowever, several other oceanic factors have been investigated as possibly affecting interannual levels of recruitment success using larval transport modelling simulations, which are not related to the large meander. These included El Niño or La Niña conditions , 30, NECWhile none of the factors investigated in modelling studies have been generally accepted as controlling interannual recruitment variations, the 2017−2018 recruitment season was unusual for its timing of glass eels catches. In contrast to the early recruitment season, eel catches started to increase and reached a maximum in March 2018 during the late recruitment season when eel catches usually decrease. The monthly catch in March and April 2018 were 2−3 times higher than in those months of the previous two years . The annThe present study investigates the unusual recruitment timing that was observed in 2018 to evaluate if the Kuroshio large meander might have been a causative factor or if other previously identified ocean circulation factors were possible influences. The extremely low catch in the early recruitment season and the exceptionally high catch in the late recruitment period are examined in relation to the presence or absence of the Kuroshio large meander and different ocean current conditions in the WNP using larval transport modelling. The model reanalysis and observed glass eel catches were used to evaluate the effect of ocean current characteristics on the late glass eel arrival by comparing two recruitment years when the Kuroshio large meander was present and two years when it was absent. Because the bifurcation latitude of the NEC has been suggested to influence eel larvae recruitment to East Asia , 14, thehttps://ovd.aori.u-tokyo.ac.jp/tides/).Annual glass eel recruitment data from 1957 to 2018 were obtained from the Japan Fisheries Agency, which included all reported glass eel catches in Japan each year. The official definition used by the Japan Fisheries Agency is that the recruitment season is from November to May of the next year. Monthly data is available from the Japan Fisheries Agency since 2016 that includes glass eel catch/input data from each prefecture, which can also include some imported glass eels from China and Taiwan. We used these monthly data pooled for all of Japan as a rough approximation of the levels and timing of recruitment to Japan/East Asia, because the abundance of catches in each area are likely geographically interrelated, and at least the low catches/inputs in Japan are directly indicative of low recruitment levels there. The Kuroshio speed anomaly was estimated from tide gauge sea level data based on geostrophy , and tidThe data-assimilative ocean circulation model known as the Japan Coastal Ocean Predictability Experiment 2 (JCOPE2) provided the three-dimensional currents and hydrological fields that were used for particle tracking in the present study. JCOPE2 was constructed from the Princeton Ocean Model with a generalized coordinate system . The modA particle-tracking method was used to simulate the movement of v-larvae of the Japanese eel during 4 recruitment seasons/years. The particles were carried by ocean currents in addition to having their own swimming behavior within the ocean currents simulated by the JCOPE2 reanalysis. The specific v-larvae swimming behavior was introduced into the experimental setup that was based on the particle-tracking scheme developed by Ohashi and Sheng . The traA random walk displacement was included in all experiments to represent unresolved sub-grid turbulent flow and other local processes . The estNumerical experiments were conducted to examine the late arrival of v-larvae transport to East Asia during the 2017−2018 recruitment season in comparison to 3 other recruitment seasons (see below). The release region and time of v-larvae were chosen according to the observed spawning area and season based on the collections of Japanese eel eggs, newly hatched preleptocephali, and spawning-condition adults along of the southern West Mariana Ridge , 39. TheThe selection of years for the simulations to examine the role of the Kuroshio large meander was based on the state of the Kuroshio meander  Figs  and 3. IDuring April in the late recruitment period, although differences were seen between years, v-larvae could make it to Japan and other recruitment areas in all cases . In 2018Although the Kuroshio large meander was speculated to be connected to the low eel recruitment in 2018 because of its occurrence when there were lower overall catches of glass eels, the large meander did not necessarily lead to less eel arrival or low recruitment, because a slightly lower overall glass eel catches occurred in 2010 when the Kuroshio took the nearshore path compared to during the previous large meander in 2005 . Low oveThe sensitivity experiments that released v-larvae within the Kuroshio south of Japan examined the effect of the large meander on the larvae crossing out of the Kuroshio , Fig 5. As the low eel catch also occurred at the upstream location of Taiwan, the cause of an extremely low catch in the early recruitment period and the sudden increase and late arrival in the late recruitment period likely originated in the offshore ocean upstream of the Kuroshio region . ConsideThe regional ocean current velocities were calculated according to the different periods/locations during the migration Figs  and 7. TPart of the v-larvae entered the STCC eddy region Figs , 4 and 6The present study explored the potential impact of the Kuroshio large meander and ocean circulation on the unusual pattern of eel recruitment in 2018 using a three-dimensional particle-tracking method . The extremely low glass eel catches observed in the early recruitment season in Japan and the higher catches in the late recruitment period in 2018 were captured by the simulations, suggesting that ocean circulation plays a crucial role in the timing of arrival of glass eels to Japan. No direct linkage between the large meander and lower recruitment was found in the simulations, because v-larvae could be transported downstream efficiently and reached southern Japan in the early recruitment period when the NEC was north-shifted in 2005 (large meander) and 2016 (no large meander), whereas v-larvae showed little or no arrival to Japan when the NEC was south-shifted in 2010 (no large meander) and 2018 (large meander). In 2018, the lower eel catches in the early recruitment season occurred when there was a weak NEC, more STCC eddies and longer retention in eddies, strong Luzon Strait intrusion, and a weak Kuroshio, which suggests there were unfavorable conditions for transporting v-larvae towards East Asia. The Kuroshio was strengthened in the late recruitment season, which transported v-larvae downstream more efficiently, resulting in increased eel catches in the late recruitment period. A schematic diagram  summarizThe Kuroshio large meander happened to occur when the unusual eel recruitment was observed in 2018. Although our experiments suggested that the Kuroshio large meander did not necessarily lead to less recruitment or late arrival, they did suggest that NEC bifurcation played a more important role in affecting the recruitment. The change of ocean conditions from the early to the late recruitment period was likely caused by a phase change of the Philippines–Taiwan Oscillation (PTO), which is based on the difference between the tropical and subtropical wind stress curl . PTO wasSeparate from the PTO, more warm eddies to the northeast of the Okinawa Islands might also contribute to the strengthening of the Kuroshio in the East China Sea and south of Japan . During A previous study also documented the late arrival of glass eels to the Sagami River of Japan  in 2010  when thehttp://nrifs.fra.affrc.go.jp/ResearchCenter/3_FOME/kuroshio/index.html). Instead of overall enhancement or reduction, the recruitment of both species seemed to be redistributed. Whitebait and skipjack were reported to have recruitment reductions in the Tokai region, but increases in areas further downstream along the Kuroshio. Late arrival of whitebait was also observed in the eastern Shikoku region. These are species that occur relatively close to Japan, and they do not make long larval migrations from far offshore like the Japanese eel does.Apart from the Japanese eel, the Kuroshio large meander was also reported to influence other fisheries species, such as whitebait (mostly engraulid fish larvae) and skipjack tuna (information from Japan Fisheries Agency based on the previous large meander event in 2005: What the larval transport modelling studies such as the present one have shown is that interannual ocean circulation changes may have an influence on the patterns or timing of glass eel recruitment. One aspect is that there may have been a long-term change in ocean circulation, such as a weakening and southward shifting of the NEC and a weakening of the Kuroshio that may reduce glass eel recruitment to East Asia . Other aWhile this first study on the effect of the Kuroshio large meander did not find evidence of this periodically occurring ocean circulation feature affecting the recruitment using a transport modelling simulation approach, this subject should be investigated further. This study did however, find indications that other ocean circulation features have the potential to influence recruitment, which is consistent with the previous studies mentioned above. Therefore, further studies are needed to evaluate the linkages between actual recruitment fluctuations based on glass eel abundances and recruitment timing, ocean conditions, and simulations of these conditions to better understand the factors affecting the recruitment of the Japanese eel.


Diagnostic ultrasound is generally considered as a safe test in pregnancy. To date there is no evidence that ultrasound has caused harm to the developing foetus. However, with the number of obstetric scans on the rise and the steep increase in acoustic output achieved by modern machines, the lack of evidence of absolute safety remains a concern. Acoustic output is under the direct control of the operator and is therefore the operator’s responsibility to keep the intensity as low as reasonably achievable. A situation analysis in the South African context was deemed necessary to determine end user knowledge and opinions on safe antenatal ultrasound practice.The aim of this quantitative descriptive, cross-sectional study was to evaluate the knowledge and practice of health practitioners who perform antenatal scans regarding safety aspects of diagnostic ultrasound.A self-administered questionnaire was distributed at two national congresses, hosted by the South African Society of Ultrasound and Obstetrics (SASUOG) and South African Society of Obstetricians (SASOG) committees.Quota non-probability sampling allowed for the identification of professional categories capable of providing information relevant to the study objectives. The sample represented a population with experience in obstetric ultrasound.Compared to international studies, South African end users demonstrated better knowledge of safety indices than their international counterparts. It is, however, discouraging that end users still demonstrate insufficient knowledge regarding factors contributing to adverse biological effects.With room for improvement, an effort should be made to comply with international standards through increased training efforts and raising awareness. The clinical benefits of obstetric ultrasound are well known and it is sometimes viewed as an extension of the human hand in pregnancy management  for obstetric ultrasound since 1992  ultrasound imaging are unlikely to give rise to thermal injury because the energy is transmitted in short pulses  introduced the Output Display Standard (ODS) to serve as an onscreen warning system for potential thermal or mechanical harm  and the South African Society of Obstetricians and Gynaecologists (SASOG). Both professional organisations represent the target population of sonographers, midwives, general practitioners (GPs), obstetricians and maternal-foetal medicine specialists who practise obstetric ultrasound in the public and private health sectors.A quota non-probability sampling method was employed by identifying professional categories capable of providing relevant information. Although some professional categories may have been over- or under-represented, the main intention was not to link the overall result to how each professional category responded, but to generalise findings to the entire population, thereby making the potential for bias irrelevant.The adapted questionnaire previously employed in an American study A total of 515 questionnaires were distributed at two national congresses. Although 159 questionnaires were returned, 38 had to be disqualified because of missing data. Statistical analysis was thus performed on 121 complete data sets.Obstetricians accounted for the largest professional component (71%), followed by sonographers (19%), GPs (7.4%) and maternal-foetal medicine specialists (2.5%). The majority (71%) had more than 6 years of experience in ultrasound; 46% were employed in the government sector and 51% practised in the private sector; 72% performed more than six scans daily. The sample in general represented a population with experience in obstetric ultrasound.Cross-tabulations were employed to interrogate the association between demographic variables  and opinions regarding safe scanning practices.p = 0.017) between the professionals’ opinions.Only 29 respondents (24%) indicated that the use of Doppler test in the third trimester should be limited and only used when medically indicated. The results yielded a statistical significant difference (p = 0.003) was recorded between professional categories and knowledge of the ALARA principle as applicable to ultrasound.The majority of sonographers (91%) were familiar with the ALARA term, while 67% of the GPs, 33% of the obstetricians and 33% of the materno-foetal medicine specialists knew the correct meaning of the acronym. A significant statistical difference (p = 0.02).Tests for association revealed that the trend for selecting the correct meaning of ALARA increased as the number of scans performed daily increased, indicating that end users who had performed more scans daily were more aware of the ALARA principle (p = 0.019) between experience in ultrasound and opinions regarding the limitation on the number of scans appropriate in low-risk pregnancies. This indicates that with more experience more caution is exerted regarding the frequency of scans in low-risk pregnancies.The Pearson’s chi-squared test for independence indicates a statistically significant association  and MI (61%) safety indices . In a muWhen questioned on the safety of B-mode and Doppler ultrasound in the three trimesters, end users indicated caution in the first trimester in general and even more caution in the application of Doppler ultrasound as did their American counterparts. Around one-third of the respondents stated that B-mode ultrasound was perfectly safe in the first trimester and could be used without any limitations , comparep = 0.017) was recorded between professional categories, with sonographers showing the greatest caution when using Doppler ultrasound in the third trimester  between professional categories, with 91% of sonographers demonstrating familiarity with the term (p = 0.02)  .There has been ongoing debate over the past three decades on the benefits of routine ultrasound screening and the ideal number of ultrasound scans performed in a low-risk pregnancy  was found between the years of experience and the number of routine scans deemed suitable during pregnancy (Financial gain and parental expectations have been identified as some of the motivating factors behind frequent ultrasound scans Helliker . In our regnancy , with moFor the ODS to be effective, it is crucial that operators are knowledgeable about the possible bio-effects of diagnostic ultrasound Marsal :214. AltAlthough the main aim of the study was achieved, the study design and research process were not without flaws or limitations. The data collection instrument was flawed by the omission of important knowledge questions because of a printing error; these are depicted in However the results indicate that there would have been no significant difference in the outcome of the study. In retrospect, a question ascertaining whether formal ultrasound training was received at any point could have been included as per the study by Houston, Allsworth and Macones :24.A follow-up study, investigating the knowledge of application specialists who represent the manufacturers of ultrasound equipment, would be of value as vendors are required by the ODS to supply end users with sufficient knowledge about bio-effects when marketing ultrasound units. The results of such a study could provide a reflection of whether manufacturers are playing their role as mandated by the FDA and whether this, in addition to possible lack of training, could be the main cause of the poor knowledge of bio-effects in our own and previous studies. Future studies could additionally focus on professional categories to ascertain whether the desired learning outcomes are being met for each discipline.With the demand for obstetric ultrasound examinations on the rise and in the absence of the assurance that ultrasound is as safe as generally believed, a concerted effort should be made to draw attention to this issue and address safety concerns that currently exists among end users of this very useful modality.


The intrathoracic transposition of the omentum (ITO) has been reported with more or less good results in various clinical circumstances but with no clear guidelines or indications.This article reviews the main clinical situations in which omento-plasty (OP) may be taken into consideration by the thoracic surgeons: mediastinitis and deep sternal infections after median sternotomy, reinforcement of the eso-gastric anastomosis after esophagectomy, prevention and treatment of the bronchial fistula after pulmonary resection, space-filling procedures for empyema, mediastinal tracheostomy, management of the infected intrathoracic vascular grafts / ventricular assist devices and heart OP. For each clinical situation we have performed a literature review with analysis of the most relevant published papers searching for an evidence-based approach for the use of the ITO/OP in thoracic surgery.OP may be an elegant solution for a wide range of problems in thoracic surgery. In the published literature, there are mainly case-reports and relatively small series published resulting in a low level of evidence for both ITO as a surgical technique by itself, as well as for the use of OP in various clinical situations involving the chest structures. The indications for its use in thoracic surgery are based more on common sense and the lack of other solutions. The omentum is well known as having an excellent plasticity and blood supply and its use has been reported in a great variety of defects with good results , 2. AlthWe have performed a literature review concerning the use of ITO / OP in thoracic surgery using the PubMed and Medline databases up to may 2018 using the following combinations of MeSH terms:  AND [Mediastinitis / Deep Sternal Infections / Median Sternotomy], [Esophagectomy / Eso-Gastric Anastomosis], [Bronchial Closure / Bronchial Fistula / Pulmonary Resection / Lobectomy / Pneumonectomy], [Empyema], [Mediastinal Tracheostomy], [Infected Vascular Graft], [Ventricular Assist Device / VAD], [Heart].We present a review concerning the indications and the main arguments for and against the use of the omentum flap (OF) in the following clinical situations: mediastinitis and deep sternal infections after median sternotomy, reinforcement of the eso-gastric anastomosis after esophagectomy, prevention and treatment of the bronchial fistula after pulmonary resection, space-filling procedures for empyema, mediastinal tracheostomy, management of the infected intrathoracic vascular grafts / ventricular assist devices and heart OP. An emphasys was put on the level of evidence for using OP in each of the aforementioned clinical situations.Mediastinitis and deep sternal infections after median sternotomy are an excellent indication for OP, which may be used alone or together with other flaps , with or without skin grafts, in order to achieve complete and definitive wound healing [ healing –8. In a  healing . The OF  healing . A speci healing .Reinforcement of the eso-gastric anastomosis after esophagectomy is a relatively new but increasingly popular indication for the ITO. This technique involves the mobilization of a relatively small OF based on the gastro-epiploic arcade and the epiploic vessels together with the greater curvature of the stomach  consisting in emergency graft replacement of the ruptured/perforated aorta and esophagectomy with mediastinal debridement to achieve local control of sepsis, as well as OP in order to protect the vascular graft which is implanted in a septic area . Endovasp = 0.06) while the 5-year event-free survival rates were 84.6 versus 33.3% (p = 0.025). However, these results should be interpretated with caution due to the small number of the patients involved [Prophylactic omental wrapping after the excision of infectious thoracic aorta aneurysms has been reported with good results in small series of patients –51. In ainvolved .Management of the infected ventricular assist devices used for end-stage heart diseases has been recently reported to benefit from OP in small series. The OF is used to wrap the pump and connection tubes, as well as to fill the infected mediastinum and/or the spaces surrounding the ventricular assist devices [ devices , 53. ConHeart omentopexy/OP in order to induce myocardial neovascularisation is an old idea. It was used as a surgical solution for ischemic heart disease before the development of modern cardiac surgery [ surgery  but it w surgery . Some re surgery , 57 but ITO/OP may be a solution for a wide range of problems in modern thoracic surgery. However, for most of the clinical situations analysed there is a low level of evidence to support its use and the indication to perform ITO/OP is based mainly on common sense and the lack of other alternatives, as well as a combination of easy mobilization and reduced associated morbidity. The possibility to perform the mobilization of the OF using a transdiaphragmatic  or lapar