Intraoperative ultrasound(iUS) and intraoperative MRI (iMRI) are effective ways to perform resection control during glioma surgery. However, most published studies employed only one modality. Few studies have used both during surgery. How to combine these two techniques reasonably, and what advantages they could have for glioma surgery are still open questions.We retrospectively reviewed a series of consecutive patients who underwent initial surgical treatment of supratentorial gliomas in our center. We utilized a full-course resection control strategy to combine iUS and iMRI: IUS for pre-resection assessment and intermediate resection control; iMRI for final resection control. The basic patient characteristics, surgical results, iMRI/iUS findings, and their impacts on surgical procedures were evaluated and reported.3 (range 1.06–16.23 cm3). 5% (2/40) of patients had permanent neurological deficits after surgery. 17.5% (7/40) of patients received further resection after the first iMRI scan, resulting in four (10%) more patients achieving gross total resection. The number of iMRI scans per patient was 1.18 ± 0.38. The surgical time was 4.5 ± 3.6 hours. The pre-resection iUS scan revealed that an average of 3.8 borders of the tumor were beside sulci in 75% (30/40) patients. Intermediate resection control was utilized in 67.5% (27/40) of patients. In 37.5% (15/40) of patients, the surgical procedures were changed intraoperatively based on the iUS findings. Compared with iMRI, the sensitivity and specificity of iUS for residual tumors were 46% and 96%, respectively.A total of 40 patients were included. The extent of resection was 95.43 ± 10.37%, and the gross total resection rate was 72.5%. The median residual tumor size was 6.39 cmThe full-course resection control strategy by combining iUS and iMRI could be successfully implemented with good surgical results in initial glioma surgeries. This strategy might stabilize resection control quality and provide the surgeon with more intraoperative information to tailor the surgical strategy. Compared with iMRI-assisted glioma surgery, this strategy might improve efficiency by reducing the number of iMRI scans and shortening surgery time. Increasing the extent of resection (EOR) significantly improves overall survival (OS) in low-grade glioma (LGG) and High-grade glioma (HGG) , 2. The IUS has been used in neurosurgery since the 1980s . The advThe characteristics of iUS and iMRI make it possible to combine them during glioma surgery. In the initial assessment, iUS has high sensitivity and specificity for detecting tumor boundaries  running the iPlan 3.0 neuronavigation software   was used : T1-weighted magnetization‐prepared rapid gradient‐echo (MPRAGE) sequence with and without gadolinium‐diethylenetriamine Penta‐acetic acid (Gd-DTPA) (2), axial T2 and T2-weighted fluid-attenuated inversion recovery (FLAIR) (3), DTI (4), functional MRI. All image sequences were imported into the iPlan neuronavigation software and co-registered before further processing. The tumor was segmented and reconstructed as a 3D model based on the T1 MPRAGE (with enhancement) or T2-weighted FLAIR (without enhancement) images. The software automatically calculated the tumor volume after segmentation. The pyramidal tract, language-related tracts , and optic radiation were reconstructed based on the DTI data using a deterministic algorithm. Functional MRI data were preprocessed using the SPM package. The results were imported into iPlan navigation software to reconstruct the Brocca area, Wernicke area, or foot, hand, and tongue motion areas. All data were exported into the navigation system to perform multimodule functional navigation during surgery. If the tumor involved the abovementioned eloquent structures, the awake craniotomy and cortical and sub-cortical mapping techniques were utilized following the strategies recommended in the literature. The positive mapping points were marked in the navigation system.The published methods were followed to ensure adequate iUS image quality . The iUSWe adopted the full-course resection control strategy to perform iUS and iMRI scans. The first iUS scan was done following dural opening 3A. The The surgeon performed serial iUS scans at intermediate stages to monitor the tumor resection process , tumor volumes were calculated by manual segmentation on FLAIR or T2 axial slices. For high-grade gliomas (HGG), a similar calculation was made using the volume of contrast-enhanced tissue on T1 MPRAGE with Gd-DTPA. The EOR was calculated as (preoperative tumor volume − postoperative tumor volume)/preoperative tumor volume. GTR means that EOR is equal to 100%. The rate of GTR was calculated.The first and second authors reviewed the long-term outcome three months after surgery by performing telephone interviews. The Karnofsky performance scale (KPS) was calculated before surgery and three months after surgery.iMRI images were analyzed by the third and fourth authors. The residual tumor volume at the first iMRI scan was calculated. The EOR, according to the first iMRI scan, was calculated using the same formula. The number of iMRI scans during each surgery was also recorded.The number of iUS scans and the iUS findings was analyzed postoperatively by the first and senior author. The tumor margins that could be marked by sulci were recorded using the following method. The tumor margins were simplified into a box without a lid with five borders  regarding the surgeon’s angle of view. The number of borders for which a sulcus could be used as a marker was noted. The number of such borders was zero for deep tumors located away from the brain surface . The number of patients in which the intermediate resection control strategy was utilized was calculated. The number of cases in which the surgical procedure was changed intraoperatively in accordance with intermediate iUS scans was calculated. The results of final control iUS for detecting residual tumors were dichotomized into “yes” and “no” during surgery and recorded. A “yes” result means that the surgical team confirmed the presence of residual tumor using iUS images. If the surgical team could not detect any residual tumor or could not make a congruent decision because of artifacts or low image quality, the result was categorized as “no.” The sensitivity and specificity of the iUS were calculated compared to the first iMRI scan results—the surgical time after anesthetization was recorded and analyzed by the first authors.Frequency distributions and summary statistics were calculated with SPSS 20.0 .A total of 40 patients were included in this study. The clinical characteristics and primary surgical results are summarized in 3.There were 22 women and 18 men, with a mean age of 48.28 ± 12.66 years. The mean preoperative KPS was 90.25 ± 12.08. The pathological results revealed a total of nine (22.5%) LGGs (WHO grade I–II) and 31 (77.5%) HGGs (WHO grade III-IV). Twenty-five (62.5%) tumors were located in the regions surrounding the eloquent areas (motor or language areas). The mean tumor volume was 61.64 ± 44.53 cm3 (range 1.06–16.23 cm3). Considering only the HGGs, the mean EOR was 97.34 ± 5.37%, the GTR rate was 77.4% (24/31). As for the LGGs, the mean EOR was 88.83 ± 18.78%, the GTR rate was 55.56%.The mean EOR was 95.43 ± 10.37%. The GTR rate was 72.5% (29/40), and the median residual tumor volume was 6.39 cmNo intraoperative complications occurred. In 57.5% (23/40) of patients, the postoperative neurological function was the same as or better than preoperatively. 42.5% (17/40) of patients had newly developed neurological deficits postoperatively; fifteen patients recovered from having neurological function equal to or better than their preoperative status during follow-up after surgery, while 5% (2/40) of patients had permanent deficits. At the final follow-up, the mean KPS was 85.0 ± 23.7 (range 30–100). Two elder patients developed severe respiratory complications at home, and one patient developed cerebral infarction two weeks after surgery. These three patients’ KPS scores decreased obviously after surgery, which lead to lower KPS scores after surgery.The first iMRI scan detected residual tumors in 37.5% (15/40) of patients. Based on the first iMRI scan results, the EOR was 93.63 ± 11.32%.17.5% (7/40) of patients with residual tumors detected on the first iMRI scan received further resection. The other eight patients did not receive further resections because of changes in neurophysiological monitoring. Finally, 10% (4/40) more patients achieved GTR. The other three of seven patients had small residual tumors left for function protection.The number of iMRI scans per patient was 1.18 ± 0.38. 17.5% (7/40) of patients received two iMRI scans. No patients received more than two iMRI scans. The surgical time was 4.5 ± 3.6 hours.In 75% (30/40) of patients, a sulcus was very close to at least one of the tumor borders and could be regarded as the marker of the tumor margins. An average of 3.8 ± 0.92 tumor borders could be marked by a sulcus.In 67.5% (27/40) of patients, the intermediate resection control was utilized to monitor the resection process. In these cases, 59.2% (16/27) had lesions adjacent to eloquent structures requiring gradual resection under intensive iUS resection control and electrophysiological monitoring. 14.8% (4/27) had large and multi-lobular tumors. 18.5% (5/27) had an irregularly shaped or multicentric tumor. 25% (7/27) had tumors that were difficult to distinguish from normal tissue under the microscope. The average number of iUS scans per patient was 3.15 ± 1.05. The time required for ultrasound image acquisition was 2-5minutes.In 37.5% (15/40) of patients, intraoperative decisions were made to change the surgical procedures based on the iUS findings. In these cases, 46.67% (7/15) were because of a mismatch between iUS and MRI, 20% (3/15) were because the relationship between the tumor and eloquent structures changed during the resection process, 20% (3/15) were because the glioma was diffuse and lacked definite margins on MR images, 13% (2/15) were because the distance to the eloquent area on iUS did not agree with the physiological monitoring results.Compared with the iMRI results, the sensitivity and specificity of iUS for residual tumors were 46% and 96%, respectively.In this study, 40 glioma patients who underwent initial surgery at our center were reviewed retrospectively. We utilized the full-course resection control strategy by combining iUS and iMRI during surgeries. The final surgical results were good and comparable with the literature data. We found this strategy might have the following advantages (1): Improving the stability of the resection control (2); Providing more information during the pre-resection phase and intermediate stage (3); Enhancing the surgeon’s ability to modify surgical procedures during surgery (4). Compared with iMRI-only surgeries, the surgery time did not increase. Based on our data, this strategy was feasible and beneficial for glioma surgeries. However, there are also a few limitations that need to be mentioned.In this study, the final EOR was 95.43%, and the GTR rate was 72.5%. 42.5% of patients had transient neurological deficits, and 5% were permanent. For comparison, We thought the results were good for these patients. For the LGGs, the mean EOR was 88.83 ± 18.78%, and the GTR rate was 55.56%. ≥ 80% EOR was achieved in 89% of the patients. Patients with LGGs resected ≥ 80% could have a significant survival advantage , 5. ConsThis study suggested that combining iUS and iMRI might make the quality of resection control more stable during glioma surgery. There was a wide variation in the reported results of glioma surgeries in the literature, no matter whether iUS or iMRI was used , 25, 26.For the iUS, image quality had been confirmed as independent factor associated with GTR. There was also association between accuracy of the resection process assessment and ultrasound image quality , 24. HowConversely, iUS may compensate for the limitations of iMRI in other kinds of situations. In comparison to MRI, iUS has a higher sensitivity for detecting tumor margins in the initial assessment unexpected residual tumors were confirmed by iMRI. Two (16%) received further resection and two iMRI scans. None had newly permanent deficits after surgery. In comparison, Bohinski et al . We achieved good surgical results safely, and with lesser iMRI scans. In 25% (12/40) of the patients, the tumors’ volume was larger than 85cmki et al  reporteder et al  reportedIn 33% 10/40) of the patients, the tumors had atypical MRI appearances. Some of them were diffused, lacking clear boundaries on MRI images (case 3). Lesions with diffuse boundaries on MRI are not also diffuse in ultrasound images . Moiyadi/40 of thIn 75% (30/40) of patients, we observed that an average of 3.8 borders of the tumor were beside the sulcus during the pre-resection iUS scan. Due to resolution issues and partial volume effects, preoperative MR images could not clearly depict these small sulci. By contrast, they could be visualized in iUS images, even when compressed by the tumor . During In 32.5% of the patients, the intermediated iUS scan was not used. These tumors always had regular shapes and clear boundaries under the microscope. Additionally, they were away from the eloquent structures. Experienced surgeons could perform perfect resections without the help of intraoperative imaging. It was also approved by the iMRI results: the residual tumors were not detected in these patients without receiving intermediate scans. Nevertheless, such tumors constituted the minority of daily gliomas. In most of the patients (67.5%), the intermediate resection control was utilized to monitor the resection process. Uncertainties about the resection process existed in most of the surgeries, even for very experienced surgeons. The intermediate iUS scans were useful in helping the surgeon get additional information, resolving the uncertainties, and modifying the surgical strategies.In 40% (16/40) of patients, intermediate iUS scans were used to assist the mapping technique when approaching the eloquent areas (Case 3). An issue with the mapping technique is that inaccurate spatial and temporal intensity might cause unexpected mechanical damage to the eloquent area . UtiliziIn the literature, the intraoperative decisions were mainly about whether further resections were needed. Further resection rates ranged from 26.1%-52.2% for the iMRI series and 25.8%-42.5% for the iUS series , 36. TheIn 17.5% (7/40) of patients, we observed a mismatch between tumor borders on iUS and preoperative MR images . We modified resection boundaries for these patients based on iUS findings because iUS had higher sensitivity for detecting glioma margins , 38. In Although introducing iUS to this group of patients might not impact EOR and GTR rates, the number of iMRI scans was significantly reduced. The mean number of iMRI scans was 1.18 per patient, and only 17.5% of patients received two iMRI scans. In comparison, previous studies using the same iMRI system report an average of 1.8 iMRI scans (two to six scans per patient in over 48% of patients) , 14. TheIn this study, we observed a reduction in surgery time compared with iMRI-assisted surgery. The average surgical time was 4.5 hours in this group of patients. Leuthardt et al. reported that the surgical time using iMRI was average 7.9 hours . MaldaunThere were some apparent limitations in implementing this strategy. One is the cost of the system. The iMRI, iUS, and navigation systems are extremely expensive. Only a few large neurosurgical centers can afford them. Another limitation stems from the steep learning curve associated with iUS, iMRI, and navigation systems. Adequate training and experience are obliged for successfully utilizing these techniques during surgery.Moreover, combining them efficiently and reasonably is also challenging, even for surgeons at the right learning curve stage. These financial and education costs will significantly limit the implementation of this strategy. However, iMRI has been more prevalent worldwide over the past few years. iUS systems are becoming smaller and more portable. As a result of these trends, this strategy is more likely to become viable in the near future.This study also has some limitations that must be addressed. This was a retrospective study based on the data from one neurosurgical center, and therefore selection bias was inevitable. The recurrent cases were not included. The sample size was also limited, especially for patients with LGG. Due to equipment limitations, we did not use other advanced iUS techniques such as elastography or contrast-enhanced ultrasound in this study. These techniques might result in different surgical results if combined with iMRI. Further studies are necessary regarding the usefulness of combining advanced iUS techniques and iMRI in a large unselected glioma cohort.3. On preoperative MRI images, anatomical structures were compressed by the large tumor and were difficult to identify. Some critical information for the surgical strategy could not be obtained from MRI images: 1. The tumor’s relationship with the insular lobe and the Sylvian fissure. 2. The location of the temporal horn of the lateral ventricle. 3. was the tumor growing into the basal ganglia through the temporal stem? On the pre-resection iUS images, the compressed insular lobe and Sylvian fissure could be clearly seen  for the publication of any potentially identifiable images or data included in this article.Conceptualization, YH, JT Methodology, YH, JT. Validation, YH, YL. Investigation, YH, YL. Resources, JT, QL, YY. Data processing, YH, YL, QL, YY. Writing—original draft preparation, YH. Writing—review and editing, JT. Visualization, YL, QL, YY. Supervision, YH, JT. Project administration, YH, JT. All authors contributed to the article 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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Ewe nutrition during gestation, either in excess or in deficit, may influence fetal development and the postnatal life of the lamb. The objective of this study was to evaluate the effects of use the of energy (ME) and energy/protein (MECP) supplementation in the ewe’s diet in the last third of gestation on maternal placental and endocrine characteristics, as well as on the behavior of neonatal lambs and productive performance. ME and MECP ewes had higher serum concentrations of triiodothyronine and cortisol on the day of lambing. However, only ME ewes had higher placental efficiency and lower total cotyledon weight. The ME and MECP diets increased birth weight at weaning and reduced the time to kneel, to try to stand, and the latency to stand of the lambs. It is concluded that overnutrition in the last third of gestation was positive for the sheep production system, with improved production rates, hormonal profile, placental characteristics and neonatal behavior. These results are valuable to society because they indicate a management strategy during the reproductive season that can be adopted by sheep producers to increase the productivity of their flocks.n = 43) with metabolizable energy (ME) and crude protein (CP) intake according to NRC (1985); ME  plus 21% ME; and MECP  plus 26% ME and CP. Body weight, body condition score, serum hormone concentrations, placental characteristics, lamb performance and behavior, and production efficiency of the ewe from lambing to weaning were measured. ME and MECP ewes were heavier before (p = 0.006) and just after lambing (p = 0.002) and had higher serum triiodothyronine (p = 0.001) and cortisol (p = 0.004) concentrations on the day of lambing. ME ewes had higher placental efficiency (p = 0.036) and lower total cotyledon weight (p = 0.011). ME and MECP diets increased both lamb birth weight (p = 0.015) and weaning weight (p = 0.009). Production efficiency at birth and at weaning was not influenced (p > 0.05) by treatments. Lamb behavior was influenced by the ME and MECP diets, reducing the time to kneel (p ≤ 0.05), to try to stand (p ≤ 0.05), and the latency to stand (p ≤ 0.005). It is concluded that overnutrition in the last third of gestation was positive for the ovine production system, with improved production rates, hormonal profile, placental characteristics, and neonatal behavior.The objective of the study was to evaluate energy or energy/protein supplementation in the ewe diet, in the last third of gestation, on maternal placental and endocrine characteristics, as well as its effects on the behavior of neonatal lambs and productive performance until weaning. A total of 128 ewes were used, and the experimental diet was fed from 100 days gestation until lambing, with the birth of 172 lambs. The ewes were distributed into three treatments: CTL (control,  The growing appreciation and demand for sheep meat, especially from young animals, has stimulated the intensification of production systems. This has made the development of new technologies to increase lamb performance essential, including for such breeds as Morada Nova. The Morada Nova is an indigenous hair sheep breed developed in Brazil with a short and silky hair coat . The MorThe placenta is the organ that performs the main interface between mother and fetus and plays an essential role in maintaining fetal growth and development by facilitating the transfer of oxygen and nutrients . PlacentDuring late gestation, the energy demands of ewes rise due to the increased nutritional requirements and the availability of nutrients for fetal growth. During neonatal life, glucose is the main energy substrate used in fetal and placental tissue metabolism . In lateThis experiment hypothesizes that increased energy and/or energy-protein intake in the nutrition of the pregnant ewe will benefit the ewe’s body reserve, placental efficiency, and the lambs’ body weight and behavior. Therefore, the objective of the study was to evaluate the influence of energy or protein/energy supplementation in ewe nutrition during the last third of gestation on placental morphometric and maternal endocrine characteristics, as well as its effects on the behavioral expression of lambs in the immediate postpartum period and on their productive performance at weaning.The study was conducted following the Brazilian Guideline for the Care and Use of Animals in Teaching or Scientific Research Activities . The expUtilizing 134 Morada Nova hair sheep ewes (3.9 ± 1.5 years), the experiment was conducted at Embrapa Pecuária Sudeste, São Carlos, Brazil. The ewes had their reproductive cycle synchronized , and after estrus detection, natural mating was performed with rams of the same breed, with libido and seminal quality previously evaluated (5 to 8 ewes/ram). Each ewe received two mates at intervals of 12 h, and gestation was checked 30 days later by real-time ultrasonography  using a 5–7.5 MHz transrectal linear transducer. A total of 128 ewes were confirmed pregnant and utilized for the experiment through lambing, with 172 lambs resulting for use in the study. Only ewes with twin pregnancies of two lambs were used in the experiment, and a similar number of sire pregnancies (rams) was assigned to each treatment.Panicum maximum cv. Aruana) until reaching 100 days of gestation. The ewes had a body weight (BW) of 41.0 ± 0.5 kg and a body condition score (BCS) of 3.0 ± 0.5 on a scale of 1–5 , and T3 Standards Set . The sensitivity and the intra-assay coefficient were 0.17 μg/dL and 12% for cortisol and 6.7 μg/dL and 11% for T3, respectively.Blood samples from the ewes were collected by venipuncture in vacuum tubes without anticoagulant  immediately after lambing. The samples were centrifuged at 1350× During the course of labor, placentas were collected immediately after ejection and stored at 5 °C for analysis within 12 h. The placenta was sanitized and weighed on a precision digital scale, adjusted to a scale of 0.01 g. After that, the cotyledons were individually dissected, and the total number of cotyledons per placenta was measured. Subsequently, all cotyledons were evaluated for the largest diameter using a digital pachymeter (graduation of 0.05 mm), and cotyledon weight and the total cotyledon weight per placenta was calculated (grams). Placental efficiency was calculated by the formula PE = FW/PW, where FW is the weight of the lamb produced (grams) and PW is the weight of the placenta (grams), for each ewe, as proposed by .0.75).Production efficiency at lambing and at weaning were calculated using the ratio between lamb weight at weaning and the metabolic weight of the ewe at lambing and at weaning, respectively ,20. The After birth, the behavior of each lamb was directly observed . Latency times for shaking the head, getting on the knees, attempting to stand up, standing up, reaching the udder, attempting to suck, and first suck, which corresponds to the first successful suck ,22, wereVitality evaluation of the lambs was performed by visual assessment and the score assigned  to each lamb based on its initial postpartum behavior, with 1 being poorly active and 5 being readily active ,25. All Data analysis was performed using the stats, car, lmtest, nlme, and emmeans package libraries, gamlss of R software, version 3.6.2 . The expGeneralized additive models for location, scale, and shape were used to analyze the variables of immediate behavior at lambing. To fit the marginal distributions for the response variables, the fitDist function (GAMLSS package) was used. A possible nonlinear relationship was tested for the birth duration variable, adding the cubic-Spline smoothing function to the model.p-value. The significance level previously adopted for the statistical analyses was ≤ 5%.Comparison between the means of the tested effects was performed by Tukey’s test. Data were reported as the adjusted mean or arithmetic mean of the sample ± standard error (SE), using the estimates (coefficients), standard errors, and p = 0.006) and after lambing (p = 0.002), but there was no effect at weaning (p = 0.338). The MECP treatment resulted in ewes with higher BW both before and after lambing , while CTL had the lightest ewes, 46.4 and 42.4 kg, respectively (p < 0.0001), and ewes with 4 or more parturitions were always heavier than the others. As there was interaction between treatment and birth order at weaning, the highest BW was observed for ME ewes with four or more previous births (p = 0.008). The BCS of ewes did not differ between treatments (p > 0.05).Treatment promoted changes in ewe BW before  for ME (250 ng/dL) and MECP (274 ng/dL) than for CTL . However, nulliparous and primiparous females showed higher T3 and cortisol release compared to ewes that had two births or more (p = 0.004). Cortisol concentrations after lambing were also influenced by the type of birth, with higher means for singleton ewes (p = 0.001).Serum T3 and cortisol concentrations were higher (p = 0.002). The primiparous of the MECP group also showed a significantly higher concentration of cortisol, compared to ewes with two or three deliveries (p = 0.001).There was a significant effect for the interaction of treatment and birth order, being observed as an increase in the concentrations of T3 and cortisol. ME and MECP promoted higher T3 release in nulliparous and primiparous ewes . Offspring sex and birth order did not influence placental weight (p > 0.05). Placental efficiency was higher for ewes in the ME group (p = 0.036) compared to CTL and MECP. The type of birth and sex of the lamb also influenced placental efficiency, being higher in ewes that gestated twins (p = 0.019), as well as in those that delivered male lambs (p = 0.016). No significant effect (p > 0.05) of lambing order was observed on placental efficiency.There was no effect of maternal nutrition on placental weight (p = 0.011) relative to CTL and MECP. Twin births increased both the number and total weight of cotyledons (p < 0.0001), which, however, were smaller in diameter than those expressed in placentas from single lambs (p < 0.001). The sex of the lamb did not affect the number of cotyledons, but placentas involving male lambs showed cotyledons with a greater diameter (p = 0.039) and greater total weight (p = 0.028). Total cotyledon weight was also greater in ewes with four or more previous parturitions compared to nulliparous ewes (p = 0.012). The birth order influenced the diameter of cotyledons (p = 0.011), so primiparous ewes had lower means compared to the other ewes. In the interaction between treatment and lambing type, there was an effect for twin gestation, with a reduction in the number of cotyledons in ME ewes (p = 0.005). The analysis of the interaction between treatment and birth order showed that the ME treatment reduced the number of cotyledons in the nulliparous, while the MECP treatment showed this effect in females with four or more births (p = 0.007).Treatments did not directly affect the total number of placental cotyledons , but totp = 0.015, p = 0.009).The ME (2.79 kg) and MECP (2.73 kg) diets resulted in heavier lambs at birth (p < 0.0001), as single gestation ewes gave birth and weaned heavier lambs (p < 0.0001), but males and females showed similar BW at weaning (p > 0.05). The birth order showed a significant effect (p < 0.0001) on birth weight, with lambs born to nulliparous females being lighter. However, ewes with more than 2 births weaned lighter lambs (p = 0.004). The analysis of the interaction of treatment with the type of birth showed a difference (p = 0.013), that being that lambs from single birth and MECP were the lightest. The interaction between treatment and sex of lambs showed higher earning capacity at weaning (p = 0.022) for males born to females in the ME group. The maternal ME diet also positively impacted the performance of male lambs at weaning.The effect of the type of birth was observed on the BW of the lambs at both times evaluated (er lambs . The sexp > 0.05) by treatments but suffered the effect of the type of birth, being more efficient (p = 0.006) for twin lambs (p = 0.039). There was no significant effect of birth order on production efficiency at lambing or weaning (p > 0.05). Analysis of the treatment interaction with the type of birth showed differences in production efficiency when dietary treatments were applied to twin-pregnant ewes, with both the ME and MECP diets being superior to the CTL group. This effect was consistent both in the immediate postpartum analysis (p = 0.004) and at weaning (p = 0.008). The interaction between treatment and lamb sex (p = 0.027) showed that the ME and MECP treatments were superior to CTL in raising the efficiency of ewes pregnant with male lambs.Production efficiency at lambing and weaning were not influenced (in lambs . ProductThe behavior of lambs born from ME and MECP ewes was different from the control. There was a 3.5 min decrease in variability for head shaking when lambs born to ewes in the ME group were compared to the CTL group. Lambs in the ME group reduced the time required to stay on their knees by 36 s. Lambs in the MECP group had reduced the time to get on their knees by 36 s and reduced the time required to try to stand up by 42 s.p < 0.0001) and 4.1 min (p = 0.005), respectively, relative to CTL. Maternal overnutrition reduced the latency to reach the udder in lambs in the ME and MECP groups by 5.9 and 4.8 min, respectively (p < 0.05). There was a reduction in variability for standing of 2.0 and 2.1 min for lambs born to ewes in the ME and MECP treatments compared to lambs born to CTL ewes, respectively (p ≤ 0.05). Additionally, variability for arrival at the udder was reduced by 2.5 min for lambs in the MECP group relative to lambs born to CTL ewes (p ≤ 0.05).ME and MECP dietary treatments significantly reduced latency to stand by 5.3 min (p < 0.0001). There was a 2.0 min reduction and 2.1 min increase in variability for first suckling for lambs born to ewes from ME and MECP treatments relative to lambs born to CTL ewes, respectively. No difference was observed between treatments for vitality score, which averaged 3.42, 3.64, and 3.39 for CTL, ME, and MECP lambs, respectively. There was also no significant variability for this characteristic (p > 0.05), regardless of the dietary treatment applied.Supplementation during gestation increased latency to first feed by 9.3 and 1.9 min for lambs in the ME and MECP treatments, respectively, relative to CTL, with opposite trends in variability , the development of insulin resistance, and greater assimilation of ingested triglycerides . ConsideDietary treatments in the last third of gestation did not influence placental weight, but this result is interesting because larger placentas demand more nutrients for their own genesis, to the detriment of the fetus . ConversME supplementation in the last third of gestation led to a significant reduction in total cotyledon weight. There is a reduction in total fetal cotyledon weight in ewes that had higher intake at the end of the first trimester of gestation . In the ME and MECP had an effect on BW of lambs after birth, corroborating previous findings that nutrition with high levels of starch increases glucose production and insulin release through the increase of propionate, which favors fetal development in the last third of gestation . The BW Although overnutrition increased the weight of neonates, only ME lambs weaned heavier, with increases of 7.8% and 8.9% in relation to the weight of CTL and MECP lambs, respectively. Excess protein in the diet can result in energy expenditure by the animal to shed nitrogen from the body; this is called the urea cost and can result in reduced animal performance of the MECP treatment compared to ME . These rThis observed difference is presumed to indicate greater postnatal anabolic capacity induced by the ME diet. At birth, male lambs were also heavier and demonstrated greater physical complexion from prenatal life, an inherent characteristic of sexual dimorphism, which was accentuated when the ME diet was employed. Interestingly, overnutrition did not favor birth weight in twin births, and the ME diet further reduced birth weight in single lambs. This particular finding aligns with that reported by , who conDisregarding the type of birth, the treatments offered in the last third of gestation did not significantly modify the production efficiency of the ewes at lambing and weaning. This fact is due to the outstanding weight and body condition of the ewes at lambing, and the weight of the lambs at birth and weaning. However, production efficiency was higher, both at lambing and weaning, in twin births, a phenomenon previously described in the literature . In factWith differential nutrient intake in the maternal diet, it was observed in lambs a reduction in the time required to perform the first attitudes of self-reflection and those required for the animal to position itself in station autonomously. However, the vitality score, a characteristic that indicates the degree of consciousness and motor activity of the neonate, was not influenced by dietary treatments. A possible explanation for this finding would be the ideal birth weight, recorded in the lambs of the three groups evaluated in this study. Birth weight has an effect on motor activity in lambs . MoreoveReducing the time required by the newborn lamb to kneel, stand, and reach the udder is of great interest, as a slow behavioral progression can have negative consequences for the neonate. After birth, getting up and suckling as quickly as possible are vital attitudes to ensure lamb survival . In the Maternal overnutrition in the last third of gestation had positive effects on ewes’ performance. Overfed ewes presented higher concentrations of triiodothyronine and cortisol after lambing and higher placental efficiency. The higher nutritional intake in the last third of gestation increased the birth weight of the lambs, and the energy diet had an additional favorable effect, which increased the weaning weight. Overnutrition of ewes reduced the time required for the newborn lamb to rise and position itself in the station but did not influence its neonatal vitality score. The diet with energy supplementation for ewes in late gestation was positive for the lamb production system.


Household air pollution from the use of biomass fuels has been associated with low birth weight in many developing countries. This study aimed to investigate the effect of indoor air pollution from biomass fuels and kitchen location on maternal reports of child size at birth in Ethiopia.A cross-sectional study design based on the secondary data analysis was used.A secondary data analysis was conducted using data from the 2016 Ethiopian Demographic Health Survey. Birth weight from child health cards and/or mother's recall was the dependent dichotomous variable. Fuel type was classified as high-pollution fuels  and low-pollution fuels . Hierarchical logistic regression was used to assess the effect of fuel type on birth weight. Adjusted odds ratios (AORs) and their 95% confidence interval (CIs) were calculated. A p-value less than 0.05 was considered significant.The prevalence of low birth weight was 17% and 26.2% among low- and high-polluting fuel users, respectively. Compared with low-polluting fuels, the use of high-polluting cooking fuels was associated with an increased likelihood of low birth weight . AOR remained at 1.7  after controlling for child variables. AOR after controlling for both child and maternal factors was 1.5 . In the final model, the association became insignificant with an AOR of 1.3 . The kitchen location, gender of the baby, mother's anaemia status, maternal chat chewing and wealth index were significant factors in the final model.In this study, the use of biomass fuels and kitchen location were associated with reduced child size at birth. Further observational studies should investigate this association using more direct methods for measurement of exposure to smoke emitted from biomass fuels on birth weight. It is a significant public health problem globally and is associated with a range of both short- and long-term consequences . Low birLow weight at birth is a major predictor of prenatal mortality and morbidity. Compared with babies born at or above the low-birth-weight cut-off (2500 g), babies born with low birth weight have a higher risk of stunting, lower IQ, a higher chance of childhood death and also have increased risk for non-communicable diseases, such as diabetes and cardiovascular disease later in life .2), formaldehyde and many other toxic polycyclic aromatic hydrocarbons (PAHs) ) were from households using biomass fuel  and 1181 (45.6%) were from households where food was cooked inside the house. The dominant type of fuel used by the households with infants in Ethiopia was wood (8383 [83.7%]) and only about 3% (274) of households used electricity .Table 1DThe proportion of low-birth-weight infants among low-polluting fuel users was 17%, while among biomass fuel users it was 26.2%. Of the total children included in this study, 2591 (25.9%) were of low birth weight and 9703 (96.9%) infants belong to households using biomass fuels. Exposure to cooking smoke is greater when cooking takes place inside the house than in a separate building or outdoors. In this study, cooking took place in a separate building for 4664 (46.6%) households, which is similar to the EDHS report that showed 47% of households cooked food in a separate building.3.2The bivariate logistic regression analysis revealed that there is a significant association between many potential predictor variables and child size at birth as indicated in 3.3We have analysed the effect of fuel type and kitchen location on maternal report of child size at birth, hierarchically. In the initial stage (model 1) when the association of cooking fuel and kitchen location was assessed with child factors, the use of biomass fuel had a significant effect on maternal report of child size at birth. Apart from the type of fuel used, the kitchen location and being a female child also had a significant effect on maternal reported birth size .In the second stage (model 2), the selected variables from model 1 were added to the maternal characteristics, such as the age of the mother at first birth, maternal educational status, BMI, anaemia level, maternal chat chewing and maternal alcohol drinking. There was a reduction in the strength of the effect of fuel type on low birth weight, but the association remained significant. Other maternal factors that significantly impacted the child's birth size included maternal anaemia, maternal chat chewing and maternal alcohol drinking. Being a female infant remained a significant effect on low birth weight in model 2 and its effect size was unchanged at this stage.In the final model (model 3), child, maternal and demographic variables were included with the exposure variables to examine the effect on low birth weight. At this stage, mothers who live in households using biomass fuels tend to have a higher likelihood of having a low-birth-weight infant, but the association was insignificant ; however, kitchen location remained a significant predictor of low birth weight. Cooking in the house  or in a separate building  were found to have an almost similar significant effect on birth size compared with cooking food outdoors. Being a female child was also a significant predictor in model 3; its strength was found to be similar and strong in all three models. Maternal age, anaemia level, pregnancy intention, chat chewing, alcohol drinking and wealth index were also found to be significant predictors of child size at birth in model 3 .4According to the descriptive findings of the study, one-quarter of children were born with low birth weight; approximately 62% of these children were ‘very small’ and 38% were ‘smaller than average’. This finding is comparable with results from rural India, where the National Family Health Survey  and 23% In Ethiopia, only 3% of the households use low-polluting fuels and the main source of fuel for most households (about 85%) is wood. This level of highly polluting cooking fuels among households in Ethiopia is higher than findings from India (72.9%) , Malawi Regarding the association between birth weight and fuel type, children of mothers from households with high-polluting fuels were about two times more likely to have low birth weight on bivariate analysis and intermediate models. However, the use of biomass fuel was not significantly associated with birth weight after all the confounding variables were controlled on multivariate analysis in the final model. A similar finding was revealed in a study by the WHO on indoor air pollution from biomass fuel use and the risk of low birth weight  and a stHowever, other findings from different studies showed that using biomass fuels was associated with a higher risk of low birth weight; using biomass fuel was associated with a two-fold increased risk on low birth weight in Lanzhou, China , and a 12.5 <25 μg/m3 and PM10 < 50 μg/m3), which can be attained through the use of cleaner fuels, well-ventilated households and kitchens, efficient cooking stoves and reduced exposure times. In most developing countries, including Ethiopia, there is limited access to improvements in this area, thus biomass fuel use together with longer exposure times, poor ventilation and unimproved cooking stoves increases the likelihood of maternal exposure to a higher level of pollutants, which, in turn, results in low birth weight [The current study identified that cooking either inside the house or in a separate building was associated with the maternal reporting of smaller child size at birth compared with cooking outdoors. Cooking food in the house was also shown to be associated with low birth weight in a study conducted in the Wolaita zone, southern Ethiopia , and theh weight ,18,23,24According to our findings, cooking inside the house and cooking in a separate building has an almost similar effect on birth size when compared with cooking outdoors. This is a clear indication that, unless efficient stoves are in place with adequate ventilation when using solid biomass fuels, the effect of cooking inside the house or in a separate kitchen might not have a difference. This is apparent in countries such as Ethiopia, where widespread use of improved cooking stoves has not taken place for various reasons, such as low incomes, lack of infrastructure, slow market penetration into remote villages, lack utilisation knowledge and information gaps .Our findings were contrary to similar research conducted in Bangladesh , where tEthiopian female infants were more likely to be of low birth weight than their male counterparts. This finding was similar to results from other studies, including research from Japan  and Nort4.1The strength of this study is that the findings can be generalised at the country level since the study utilised data from a nationally representative household survey. However, children were classified as low birth weight or not low birth weight based on the mother's subjective judgment, which might introduce measurement bias on the outcome ‘low birth weight’. This could have implications for the results. In addition to the reliance on self-report of birth size, the cross-sectional design might pose problems in establishing the temporal link between exposure and outcome. This study assumed that maternal exposure to biomass fuels was a phenomenon that occurred repeatedly over a long time before pregnancy, which might not always be the case.4.2The use of biomass fuel and kitchen location was associated with child size at birth. Our findings have important programme and policy implications for countries such as Ethiopia, where large proportions of the population rely on high-polluting biomass fuels for cooking. Furthermore, future studies should investigate the association using more direct methods for measurement of exposure to smoke emitted from biomass fuels on birth weight.This secondary analysis was exempted from ethical review approval because it used publicly available, de-identified data. However, a request to access datasets from the DHS was made, and a letter of permission to use the data set was obtained before the analysis was conducted.The authors have no support or funding to report.http://dhsprogram.com/data/available-datasets.cfm.The data are available from the Demographic and Health Survey programme website. These data are publicly available online and can be accessed at the following website by selecting the specific country, Ethiopia. Conceptualisation: Girum Gebremeskel Kanno; Formal analysis: Girum Gebremeskel Kanno and Sewitemariam Desalegn Andarge; Methodology: Girum Gebremeskel Kanno and Sewitemariam Desalegn Andarge; Project administration: Girum Gebremeskel Kanno; Supervision: Adane Tesfaye Anbesse, Mohamed Feyisso Shaka and Miheret Tesfu Legesse; Writing – original draft: Girum Gebremeskel Kanno and Mohamed Feyisso Shaka; Writing – review & editing: Girum Gebremeskel Kanno, Mohamed Feyisso Shaka and Adane Tesfaye Anbesse, Miheret Tesfu Legesse.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


Early access to antenatal care and high-cost technologies for pregnancy dating challenge early neonatal risk assessment at birth in resource-constrained settings. To overcome the absence or inaccuracy of postnatal gestational age (GA), we developed a new medical device to assess GA based on the photobiological properties of newborns’ skin and predictive models.This study aims to validate a device that uses the photobiological model of skin maturity adjusted to the clinical data to detect GA and establish its accuracy in discriminating preterm newborns.A multicenter, single-blinded, and single-arm intention-to-diagnosis clinical trial evaluated the accuracy of a novel device for the detection of GA and preterm newborns. The first-trimester ultrasound, a second comparator ultrasound, and data regarding the last menstrual period (LMP) from antenatal reports were used as references for GA at birth. The new test for validation was performed using a portable multiband reflectance photometer device that assessed the skin maturity of newborns and used machine learning models to predict GA, adjusted for birth weight and antenatal corticosteroid therapy exposure.The study group comprised 702 pregnant women who gave birth to 781 newborns, of which 366 (46.9%) were preterm newborns. As the primary outcome, the GA as predicted by the new test was in line with the reference GA that was calculated by using the intraclass correlation coefficient . The paired difference between predicted and reference GAs was −1.34 days, with Bland-Altman limits of −21.2 to 18.4 days. As a secondary outcome, the new test achieved 66.6% (95% CI 62.9%-70.1%) agreement with the reference GA within an error of 1 week. This agreement was similar to that of comparator-LMP-GAs . The discrimination between preterm and term newborns via the device had a similar area under the receiver operating characteristic curve  compared with that for comparator-LMP-GAs . In newborns with absent or unreliable LMPs (n=451), the intent-to-discriminate analysis showed correct preterm versus term classifications with the new test, which achieved an accuracy of 89.6% (95% CI 86.4%-92.2%), while the accuracy for comparator-LMP-GA was 69.6% (95% CI 65.3%-73.7%).The assessment of newborn’s skin maturity (adjusted by learning models) promises accurate pregnancy dating at birth, even without the antenatal ultrasound reference. Thus, the novel device could add value to the set of clinical parameters that direct the delivery of neonatal care in birth scenarios where GA is unknown or unreliable.RR2-10.1136/bmjopen-2018-027442 Being born before 37 weeks of gestation, which is preterm birth, is the leading cause of childhood mortality. The global preterm birth rate is approximately 11%, with a particularly high frequency in low- and middle-income countries, in association with maternal education, race, and ethnic origin . The firSome pregnancy-dating troubles arise from antenatal care. Government policies and best practices advise pregnant women to plan pregnancy to include early access to antenatal care for pregnancies to be safely monitored until birth . HoweverReliable pregnancy dating has an impact on measuring the global burden of preterm birth and the associated risks ,12. ImprThe new test explored in this study is an innovative approach used to estimate GA based on the photobiological properties of the newborn’s skin and by learning predictive models enhanced with clinical variables . It beinThis study aimed to validate a new medical device used to assess GA through the photobiological model of skin maturity adjusted to clinical data and to determine its accuracy in detecting preterm newborns. We tested the hypothesis of equivalence between GA measured by this new test and by pregnancy-dating comparators calculated using ultrasound examinations and the LMP.This study was a multicenter, prospective, intention-to-diagnosis clinical trial investigation with a single group, single-blinded, and single-arm, using a reference standard. This paper adheres to the Transparent Reporting of a Multivariable Prediction Model for Individual Prediction or Diagnosis for completeness and clarity . IntentiThis report examined the primary and secondary outcomes of data concerning GA prediction and clinical safety of the novel device. Secondary outcomes related to lung maturity prediction are currently under analysis for further publication. The following five Brazilian urban referral centers for high-complexity perinatal care took part in the study: Clinical Hospital—Universidade Federal de Minas Gerais (as coordinator), Minas Gerais State; Sofia Feldman Hospital—Minas Gerais State; Hospital da Universidade Luterana do Brasil—Rio Grande do Sul State; Hospital Materno-infantil de Brasília—Federal District; and Hospital Universitário da Universidade Federal do Maranhão—Maranhão State.A prospective concurrent and sequential process enrolled newborns during the first 24 hours of life. The first enrollment occurred on January 2, 2019, and the last occurred on May 30, 2021. Eligibility criteria, participants’ timeline, and procedures followed the research clinical protocol . In shorThe coordinating unit trained 15 health professional examiners following good clinical practice as set forth by the Brazilian Regulatory Health Agency’s recommendations. Standard operating procedures were mandatory to guide the enrollment process, skin assessment, and data collection . ClinicaAn automated algorithm in the data collection system  blinded The intervention in this clinical trial was a test performed with a novel device that processes the backscattered signal acquired from the skin of the newborn’s sole with clinical variables to predict the GA. Its development includes steps from the workbench to clinical experimentation, as described earlier . SimilarSkin assessments occurred with the newborn inside incubators, incubators-radiant warmers, warming pad-bassinets, standard cribs, or in the mother’s lap to ensure minimum manipulation and to avoid unbalancing the clinical conditions. The sensor touched the sole 3 times, following complete disinfection with alcohol. A total of 14 minimum viable products were produced in this study . At the r=0.79, P<.001; The device used an algorithm to predict GA, as previously described, and was duly patented . We asseThe standalone newborn skin reflectance value was adjusted for clinical variables. The current data set the groundwork for improvements in the model for prediction of GA with the use of machine learning models as part of the research protocol. The analytical pipeline is detailed in R2 of 0.732 and a mean absolute error (MAE) of 1.688 weeks (11.8 days). In addition, considering birth weight, the model achieved an even better performance in terms of R2 of 0.878, with an MAE of 1.147 weeks (8.0 days). This new model, with 3 predictive variables, was the one validated in this study. However, 3 GA predictions had ACTFM data imputation by the machine learning model owing to missing information because of failures in the antenatal record available at maternity admission.Models’ performance with different covariates, including intermediate analysis considering factors such as incubator stay, sex, and jaundice, is presented in The primary outcome was the agreement between the GA predicted by the device and reference GA. The secondary end point was the accuracy of the device in the identification of preterm newborns, considering thresholds at 37, 32, and 28 weeks of pregnancy. Moreover, the proportion of preterm newborns correctly detected at birth within a 1-week error margin. Another secondary end point was the comparison of differences between predicted GA and GA calculated by a second ultrasound examination after 13 weeks and 6 days of gestation and before 22 weeks via comparator-ultrasound-GA and with the comparator-LMP-GA. This outcome was intended to simulate the performance of the device in scenarios without the reference and to compare the agreement between the established methods for GA calculation and the new test. The safety of the device is still a derived end point which refers to the reporting of unexpected medical events, unintended illness or injury, or adverse clinical signs in newborns, users, or others, regardless of whether they are related to the investigated product. The users answered 9 questions regarding issues with the medical device, after each skin acquisition .U test, and mean paired differences were used to compare interest groups of preterm and term newborns. P values of <.05 were considered suggestive of statistical significance. SPSS software  was used for statistical analysis of the data.Descriptive analyses of the newborn’s clinical characteristics and intervention measurements were performed. Regarding the primary end point, the agreement among different methods for GA at birth determination was calculated using the intraclass coefficient (ICC) correlation, Bland-Altman intervals, and the paired day difference to reference GA. Regarding the accuracy of the predicted GA by the device in identifying premature newborns, the area under the receiver operating characteristic curve (AUROC) at a CI of 95% described the new test’s discrimination and diagnostic parameters. The chi-square test, Mann-Whitney The local independent ethics review board approved the research protocol, registered under the number CAAE 81347817.6.1001.5149 at the Brazilian National Research Council. In addition, parents signed an informed consent form on behalf of the newborns before participating.Of the 791 potentially eligible newborns, 2 were under Rh alloimmunization during pregnancy, which was considered an exclusion criterion . In thisThe study group comprised 702 pregnant women who gave birth to 781 newborns. Despite early access to antenatal care with a median value of 12 (IQR 4) weeks , only 29P<.001 (paired Wilcoxon test). However, when available, the comparator-LMP-GA had a median of 37.4 (IQR 6.8) weeks, similar to the reference GA, P=.282 (paired Wilcoxon test). The frequency of preterm birth was 46.9% (366/781), 47.1% (368/781), and 45.6% (310/680) according to the reference GA, comparator-ultrasound-GA, and comparator-LMP-GA, respectively. The frequency of postterm birth was 0.1% (1/781), 0.3% (2/781), and 4% (27/680) with reference to GA, comparator-ultrasound-GA, and comparator-LMP-GA, respectively. On the other hand, the data quality of the LMP recall revealed that the most frequent digit preferences were for days 5 (8.3%), 15 (6.7%), 20 (7.2%), and 25 (4.7%). These frequencies had significant differences when compared with the day adjusted to the reference GA .The distribution of GA as calculated according to the different references corroborated some differences among the established methods of antenatal dating, as shown in the overlapped histogram, in weeks of gestation . In thisDigit preference analysis searched for the tendency of round-numbered days of the menstrual period, considering digits, typically multiples of 5 and 10. This was determined by comparing the observed and expected counts for each day of a month. The Cochran Q test for k-related samples compared the LMP with the day adjusted to the reference GA. We removed duplicate data from twins, and observations on day 31 were removed during the statistical test. The dotted line corresponds to the frequency expected for each day for 30 days per month.P=.008). Analyzing the day digit of the LMP adjusted by the second ultrasound examination performed on data after 13 weeks and 6 days of gestation and before 22 weeks (comparator ultrasound), there were no significant differences when compared with the day adjusted to the reference GA (P=.20).Analyzing the day digit of the LMP informed by the woman, the most frequent digit preferences were for days 5 (8.3%), 15 (6.7%), 20 (7.2%), and 25 (4.7%). These frequencies had significant differences when compared to the day adjusted to the reference GA  days, as well as by 0.81 (95% CI −1.50 to −0.11) days, and by 2.35  days in relation to the ultrasound and LMP-GA comparators, respectively. In the meantime, the ultrasound GA comparator underestimated the reference GA by −0.53 (95% CI −0.88 to −0.19) days. The end points of the Bland-Altman 95% limits of agreement were the 2.5th percentile and 97.5th percentile for the distribution of the difference between paired measurements . TherefoThe boxplots in Considering an overlap of 95% CIs in AUROC, the new test using the device had similar performance to comparator-LMP-GA in discriminating preterm against term newborns at all cutoffs, respectively, AUROC 0.973 (95% CI 0.963-0.982) and 0.957  newborns. In scenario 2, we grouped the newborns whose mothers had reliable LMP . ConcernThe lack of a reliable LMP in scenario 1 resulted in low discrimination accuracy of 69.6% (95% CI 65.3%-73.7%) with the comparator-LMP-GA. Nevertheless, 89.6% (95% CI 86.4%-93.1%) of the newborns were correctly classified as preterm or term using the device. Great accuracy using any available method for GA estimation was observed in scenario 2, where the LMP was reliable. In such a scenario, we see similar device accuracy of 93.9% (95% CI 90.8%-96.3%) when compared with the accuracy of comparator-ultrasound-GA of 97% (95% CI 94.5%-98.5%) and comparator-LMP-GA of 93.4% (95% CI 94.5%-97.9%). The overall analysis includes crosstabs in There were no reports of unexpected medical events, unintended illness or injury, or unfortunate clinical signs in subjects, users, or others related to the investigational product. Two devices were replaced because of an unintentional drop.The main contribution of this clinical trial is the validation of a new approach for GA estimation, regardless of fetal ultrasound measures by demonstrating accurate outcomes. Based on birth weight, ACTFM exposure data, and use of a handled medical device to assess skin maturity and process algorithms, 91.4% 714/781) of newborns were correctly classified. A reliable antenatal age is a prerequisite for preterm newborn classification in birth care settings and is the first step in delivering the necessary care, considering the risks of prematurity. A term newborn, together with good tonus, breathing, or crying, is an essential element to determine steps of newborn resuscitation . Althoug1 of newbIn this combined study covering the enhancement of the prediction model for postnatal GA and validation of the device, we believe that the application of k-fold cross-validation with the use of machine learning algorithms provided accurate predictions . While lThus, data science algorithms have thus emerged with the aim of qualifying pregnancy dating. High-performance reports using learning models based on antenatal ultrasound predictors  contradiR2 and low MAE, thereby avoiding the standalone model with birth weight  was lower than the comparator-LMP-GA. Moreover, this device could provide a GA to handle situations without ACTFM information as a potential tool in low-resource birth settings. Considering the simulated scenario with LMP either absent or unreliable (n=451 newborns), the new test had a better performance than the comparator-LMP for the estimation of GA. This result highlighted the context of use of this medical device, as the GA based on memory recall of the LMP missed 68 out of 199 preterm newborns, expressing a lower sensitivity when we applied the intent-to-discriminate analysis.Exposure to ACTFM played an uncertain role in the predictive model. Nevertheless, there was a rationale to consider its importance to adjust the skin reflection. Antenatal corticosteroids to improve newborn outcomes are an evidence-based intervention recommended for women at risk of preterm birth . HoweverCurrent approaches to calculating GA are sensitive to data quality, resulting in an inappropriate classification of prematurity . This stRegarding the generalizability of the outcomes, this multicenter trial gathered referral perinatal units from Brazil’s northern, central, southwestern, and southern regions. This collaborative evaluation contributed to obtaining a sample of a mixed population of newborns with high miscegenation and involved 15 examiners who attended good clinical practice training. Both intraobserver and interobserver errors of the measurements were low, in line with previous results . The numThe assessment of newborn’s skin maturity adjusted by learning models promises accurate pregnancy dating at birth, even without the antenatal ultrasound reference. Identifying preterm newborns is the first step toward meeting their needs. The global rate of neonatal mortality is approximately 6700 neonatal deaths daily, mostly from preventable or treatable conditions in scenarios without adequate health care . Without


A pseudoaneurysm of the splanchnic vessels is considered to be rare, and in particular, very few cases of pseudoaneurysm in the ileocolic artery are reported. Here, we report a case of rupture of a pseudoaneurysm of the appendicular branch of the ileocolic artery after laparoscopic appendectomy.A 52-year-old man was diagnosed as having phlegmonous appendicitis, and an emergency laparoscopic appendectomy was performed. Bleeding from the inter-appendicular ligament during detachment of adhesions was stopped by white coagulation and Z-suture, and the inter-appendicular ligament was treated. The postoperative course was uneventful, and there were no adverse events or findings suggestive of abscess formation. On postoperative day 30, he presented with a ruptured pseudoaneurysm of the appendicular branch of the ileocolic artery. A definitive diagnosis was made by computed tomography, and emergency interventional radiology was performed with hemostasis achieved by coiling. The patient’s postprocedure course was favorable, and he was discharged with no adverse events, such as intestinal ischemia.We experienced a case of delayed pseudoaneurysm rupture after laparoscopic appendectomy. Care must be taken when handling the appendicular artery during the procedure, and the potential for pseudoaneurysm formation should be considered at postoperative follow-up. A pseudoaneurysm is pathologically defined as a rupture of the vascular wall and accumulation of hematoma in perivascular connective tissues. A pseudoaneurysm of the splanchnic vessels is considered to be rare. In particular, very few cases of pseudoaneurysm in the ileocolic artery have been reported. Here, we report a case of rupture of a pseudoaneurysm of the appendicular branch of the ileocolic artery after laparoscopic appendectomy.3/μL) and a slight increase in C-reactive protein (CRP: 1.07 mg/dL), with other values within normal limits. Abdominal contrast-enhanced computed tomography (CT) revealed swelling of the appendix and a stercolith at the root of the appendix  3 after admission. The postoperative course was free of adverse events, and he was discharged from hospital on POD 5. On POD 20, he visited our hospital outpatient clinic. Blood testing was negative for inflammatory reaction, the abdominal findings were normal, and the outpatient examination was completed. The pathological diagnosis was phlegmonous appendicitis.3/μL) and a slight increase in CRP (0.91 mg/dL). However, no anemia was observed at this point. Abdominal contrast-enhanced CT revealed fluid accumulation in a high-density area from the ileocecum to the hepatic surface. A pseudoaneurysm was found near the ileocecum with extravasation . A physical exam found him in a cold sweat with localized severe tenderness in the right lower quadrant. Blood tests showed an increase in WBC (9.4 × 10When the iliac artery was catheterized from the superior mesenteric artery (SMA) and angiography was performed, a pseudoaneurysm was visualized in the periphery of the appendicular branch Fig. a, c. A mThe patient’s post-IVR vital signs remained stable. On day 1 of admission, a decrease in his Hb to 7.5 g/dL was found, and 4 units of red blood cells were administered to improve the anemia. On POD 3, the patient began meals, and even after the patient started eating again, no findings suggestive of mesenteric ischemia were noted. The patient’s outcome was good, and he was discharged on POD 6. About 3 years have passed since discharge, and his course has been complication free.A pseudoaneurysm may threaten life due to hemorrhage, and thus, an accurate and quick diagnosis is needed. Pseudoaneurysms of the splanchnic vessels are rare. Few cases have been reported collectively, and in a systematic review , only 15Pseudoaneurysm occurs as follows. Rupture of the arterial wall causes blood flow between the arterial lumen and perivascular connective tissues. A blood-filled cavity forms outside of the vascular wall, and leakage of blood is blocked by thrombus formation . In pancWhile about 80% of true aneurysms in the visceral artery are asymptomatic, pseudoaneurysm is frequently symptomatic. The most serious complication of pseudoaneurysm is hemorrhage. The mortality rate of patients with hemorrhage is high at between 12.5% and 37% , and symAngiography is reported to be the best-suited means of diagnosis, and real-time assessments with 100% sensitivity are possible. This is followed by CT 67%) and ultrasound (50%) . Because7% and ulThe final consultation for our patient was the outpatient examination on POD 20 after the first admission, but rupture of the pseudoaneurysm rupture was found on POD 30. For the other two reported cases, pseudoaneurysm rupture occurred 3 weeks after the operation and 36 h after the operation, respectively. When considering the risks of delayed pseudoaneurysm rupture, outpatient follow-up may need to be longer than usual if the appendix was highly inflamed and intraoperative treatment of the appendicular artery was difficult.We experienced a case of delayed rupture of a pseudoaneurysm of the appendicular branch of the ileocolic artery after laparoscopic appendectomy. Care must be taken when handling the appendicular artery during the procedure, and the potential for pseudoaneurysm formation should be considered at postoperative follow-up.


Globally, 15 million children are born preterm each year and 10.7 million are born at term but with low birthweight (<2500 g).The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) cluster-randomized trial enrolled 5280 pregnant women between 22 November 2012 and 27 March 2015 to test the impact of improved water supply, sanitation and hygiene, and improved infant feeding, on child growth and anaemia. We conducted a secondary analysis to estimate the prevalence and risk factors of miscarriage, stillbirth, preterm birth, size small for gestational age (SGA), low birthweight (LBW), perinatal mortality, and neonatal mortality, and to estimate the effects of adverse birth outcomes on infant survival and growth. The prevalence of adverse birth outcomes was: miscarriage: 5.0% ; stillbirth: 2.3% ; preterm birth: 18.2% ; SGA: 16.1% ; LBW: 9.8% ; and neonatal mortality: 31.4/1000 live births . Modifiable risk factors included maternal HIV infection, anaemia, lack of antenatal care and non-institutional delivery. Preterm infants had higher neonatal mortality [risk ratio (RR): 6.1 ], post-neonatal infant mortality [hazard ratio (HR): 2.1 ] and stunting at 18 months of age [RR: 1.5 ] than term infants; 56% of stillbirths and 57% of neonatal deaths were among preterm births. Neonatal mortality and stillbirth are high in Zimbabwe and appear to be driven by high preterm birth. Interventions for primary prevention of preterm birth and strengthened management of preterm labour and ill and small neonates are required to reduce neonatal mortality in Zimbabwe and other African countries with similar profiles. Key MessagesGlobally, 15 million children are born preterm and 10.7 million are born at term but weigh less than 2.5 kg. These two groups of infants comprise 20% of births but 50% of neonatal deaths.In this population-based sample of more than 5000 pregnant women and their infants in rural Zimbabwe, 2.3%  of pregnancies ended in stillbirth and neonatal mortality was 31.4/1000 live births . Among infants who provided gestational age and weight at birth, 18.2%  were born preterm; 57% of both stillbirths and neonatal deaths were among preterm infants.Neonatal mortality is high in Zimbabwe and appears to be driven by high preterm birth.Interventions to reduce preterm births and to strengthen pre-emptive management of preterm labour and care for small and ill neonates are urgently required to reduce neonatal mortality in Zimbabwe and other African countries with similar profiles.,,Globally, 15 million infants are born preterm (<37 weeks’ gestation)Zimbabwe has stubbornly high NNM: in 2019 it was 32/1000 live births,2)The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial was a community-based study in two rural districts  of Zimbabwe which enrolled 5280 pregnant women at a median gestational age of 12 weeks  to Option B+  in November 2013. The MoHCC also provides ‘waiting women’s shelters’ at health facilities to accommodate women near the end of their pregnancy, to facilitate institutional delivery. Infant birth date, weight and delivery details were transcribed from health facility records. The trial provided Tanita BD-590 infant scales to all health institutions in the study area and trained facility staff on weighing newborns at birth. Recumbent length was measured to the nearest 0.1 cm using a Seca 417 infantometer  and weight to the nearest 10 g  at 18 months of age. At the 18-month trial endpoint, mothers and infants were visited anywhere in the country. However, in view of the household-based nature of the WASH interventions, intermediate visits were done only when the mother was available in the household where she consented.Serious adverse events, including fetal loss (miscarriages or stillbirths) and neonatal deaths, were ascertained by research nurses or VHWs or reported to the study by the mother herself; a senior nurse collected event details which were reviewed by the study physician (A.J.P.) before reporting to institutional review boards (IRBs). Adverse birth outcomes were defined as: miscarriage ; stillbirth ; preterm birth (live birth before 37 weeks’ gestation); LBW (birthweight <2500 g); SGA  were estimated using a bootstrap resampling technique with 1000 bootstraps.2 in a validation study among pregnant women in South Africa who were <20 weeks’ gestation.Infant lengths and weights at 18 months were converted to Z scores using WHO reference standards; stunting and wasting were defined as LAZ <−2 and WLZ <−2, respectively.To identify risk factors for adverse birth outcomes, we pre-specified two groups of variables. Group 1 included factors reported in previous epidemiological and clinical studies. For all outcomes, these included maternal age , height, mid-upper arm circumference, HIV infection and anaemia , where the reference category was Term, NBW, AGA, Term/NBW, or Term/AGA, as relevant. Hazard ratios for post-neonatal mortality for these categories were estimated using Cox proportional hazard model with standard errors adjusted for the clusters. All statistical analyses were performed using STATA version 14.Over the recruitment period, the MoHCC VHWs recorded a total of 40 444 women aged 15–49 years as residing in the two study districts . Of thesAt baseline women were, on average, 26.3 years old, and had completed more than 9 years of schooling; 95.2% were married; 15.9% were living with HIV; and 20.1% were anaemic . Nearly IJE online). Maternal age ≥35 years was the only independent risk factor in the adjusted model. There were 158 [3.2% ] second trimester miscarriages; risk factors were similar when analyses excluded first trimester miscarriages (data not shown). The prevalence of stillbirth was 2.3%  (IJE online). Antenatal care, singleton pregnancy, improved latrine ownership  and maternal anaemia were protective against stillbirth. Notably, 63/113 (56%) of the stillbirths occurred before 37 weeks’ gestation (data not shown). Perinatal mortality was 47.0/1000 births  (IJE online). Compared with infants born at term with normal birthweight, risk of perinatal mortality was higher for infants born small or prematurely and highest for infants born small and prematurely, where small size was based on either SGA or LBW (IJE online).Among 4936 women enrolled into the trial before 28 weeks’ gestation, 249 [5.0% ] miscarried ; among these infants, 666  were preterm births . In the Among the 3667 infants with available birthweight and gestational age data, 591  were SGA at birth . In adjuOf the 4304 infants who provided birthweight, nearly 10% were LBW  . In adjuThere were 152 neonatal deaths among the 4843 live births  . In the As reported above, our primary estimate of preterm birth, based on the 3667 (75% of live births) infants who provided birthweight and a plausible gestational age, was 18.2% . Infants excluded from this estimate included 539 infants missing birthweight and 637 missing gestational age . Of the 539 infants missing birthweight, 186  were born preterm based on last menstrual period. To interpret this high preterm birth rate, we analysed place of delivery and neonatal mortality for all live births and the three subgroups of infants . CompareInfant survival and growth outcomes associated with gestational age and size at birth were analysed among the 3667 infants with complete data. NNM was higher among preterm compared with term births ; preterm infants comprised 57% of the neonatal deaths. Similarly, the NNM was higher among LBW compared with NBW . Among infants who were both preterm and LBW, NNM was of 201.1/1000 Live births: these infants comprised just 5% of the population but contributed 42.5% of the neonatal deaths. Similarly, NNM among all SGA infants was 20% greater than among all AGA infants and was highest among infants with both preterm birth and SGA .Preterm, LBW and SGA infants who survived the neonatal period remained at increased risk of death in the post-neonatal period of infancy . StuntinThe high neonatal mortality among infants in the SHINE cohort is comparable to the national average estimated in 2019 (31.4/1000 and 32/1000 live births,,Based on our findings from SHINE, we posit that Zimbabwe’s stubbornly high neonatal mortality is largely driven by a high rate of preterm births. In our primary analysis, the preterm birth prevalence was 18.2%, one of the highest in the world.Preterm birth has been universally resistant to change. Globally, the prevalence of low birthweight declined from 17.5% to 14.6 between 2000 and 2015 %,Our study has several limitations. First, this was a secondary analysis of a cluster-randomized trial whose primary objective was to test the impact of WASH and IYCF on children at 18 months of age. The pregnancy surveillance undertaken to identify women early in pregnancy resulted in many women booking for antenatal care earlier than they would have otherwise, which hastened initiation on PMTCT interventions for HIV-positive women and may have resulted in earlier detection and treatment of other problems. Beyond this, the trial neither provided enhanced antenatal care nor did it assess the quality of antenatal care. Second, about one-third of the pregnancies identified by VHWs were not referred to SHINE, providing opportunity for selection bias. The main reason for non-referral was ineligibility due to gestational age beyond the cut-off in place at the time. Since nulliparous women have a tendency for higher preterm birth and SGA deliveries than most multiparous women,In the past two decades, there has been a great deal of progress in improving clinical management of infants with preterm birth in LMICs, with strategies including antenatal corticosteroids, maternal and neonatal antibiotics, neonatal stabilization and resuscitation and prevention of hypothermia.http://ClinEpiDB.org].Data underlying this article from the SHINE trial are available in ClinEpiDB at [IJE online.dyab248_Supplementary_DataClick here for additional data file.


Present review paper aims to understand role of diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) in diagnosis of traumatic axonal injury (TAI), induced by head trauma, in individual patients with a concussion or mild traumatic brain injury (mTBI). Precise information on presence and severity of TAI in brain is necessary for determining appropriate therapeutic strategies. Several hundred DTI-based studies have reported TAI in concussion or mTBI. Majority of these DTI-based studies have been performed in a group of patients, whereas case studies that have reported TAI in individual patients with a concussion or mTBI are fewer. Summary of these DTI-based studies for individual patients is as follows: DTI can be used as a non-invasive tool for determining presence and severity of TAI in individual patients with concussion or mTBI. However, for diagnosis of TAI in an individual patient, several conditions are required to be met: no past history of head trauma, presence of possible conditions for TAI occurrence during head trauma, development of new clinical features after head trauma, and DTI observed abnormality of a neural structure that coincides with a newly developed clinical feature. However, further studies for a more precise diagnosis of TAI in individual patients should be encouraged. Traumatic brain injury (TBI) is classified as a concussion when a patient suffers a loss of consciousness (LOC) for less than six hours following the trauma, whereas when LOC lasts for six hours or more, it is classified as a diffuse axonal injury ,2. ConcuTraumatic axonal injury (TAI) is a type of TBI involving injury to axons mainly induced by indirect shearing forces during acceleration, deceleration, and rotation of the brain following head trauma ,11,12,13The aim of this study is to review the diagnostic approach to diagnose TAI in individual patients with concussion or mTBI based on the previous DTI studies. The diagnosis of TAI in individual patients with concussion or mTBI is clinically important. Precise information on the presence and severity of TAI for a specific neural structure in the brain is necessary to predict prognosis and to determine appropriate therapeutic strategies including the administration of drugs, rehabilitative exercises, or use of neuromodulation techniques such as repetitive transcranial magnetic stimulation or transcranial direct current stimulation ,71. The We have reviewed the role of DTI in the diagnosis of TAI with clinical correlation in individual patients with concussion or mTBI, based on available published literature.DTI or DTT-based studies that demonstrated TAI with clinical correlations in individual patients with concussion or mTBI were searched. The electronic databases (MEDLINE database (PubMed), Web of Science, and ScienceDirect) search and manual search were used to include the case or case series studies published from 1992 until 20 May 2022. The search strategy for identifying potentially relevant articles was based on the subject heading and keywords/abbreviations with synonyms as follows: (“diffusion tensor imaging” OR “diffusion tensor tractography” OR DTI OR DTT) AND (“concussion” OR “mild traumatic brain injury” OR mTBI). The inclusion criteria for subjects were limited to studies involving individual human subjects with concussion or mTBI. Overall, 52 studies were selected to review  17,18,1,71,72,74Among various DTI or diffusion tensor tractography (DTT) parameters, the fractional anisotropy (FA) indicates the state of white matter organization and is a measure of the degree of the directionality and integrity of the white matter microstructures, the mean diffusivity : the magnitude of water diffusion, and tract volume  is the number of voxels within a neural tract which represents the number of fibers within a neural tract ,86,87,88Two types of estimation methods for DTI have been commonly used to demonstrate TAI in concussion or mTBI: (1) DTI region of interest (ROI) method, which involves the measurement of DTI parameters in a certain ROI of the brain on two-dimensional DTI images, and (2) DTT method, which reconstructs the neural tracts three-dimensionally  17,18,1,86,87,88In the detection of TAI in individual patients with concussion or mTBI, the DTT method has the following advantages compared to the DTI ROI method: First, the DTI ROI method can yield false results due to the high individual variation of the anatomical location of the neural structures in the human brain . Second,However, the DTT method may underestimate or overestimate the neural tracts due to regions of fiber complexity, crossing of fibers that can prevent the full reflection of the underlying fiber architecture, and incorrect analysis conditions  ,86,91,92After the introduction of DTI, more than 50 papers have reported TAI with clinical correlations in individual patients with concussion or mTBI ,72,74,81Flow sheet 1. Diagnostic approach of traumatic axonal injury of a neural tract in an individual patient with concussion or mild traumatic brain injury  . Th. Th62]. This study reviewed the role of DTI in the diagnosis of TAI with clinical correlations in individual patients with concussion or mTBI. In summary, DTI for a specific neural structure or DTT for a specific neural tract can be used as a non-invasive tool for determining the presence and severity of TAI in individual patients with concussion or mTBI ,72,74,81


The calculation results indicate that for the Co(i)/iPrPNP catalytic system, the undirected pathway is 2.9 kcal mol−1 more favoured over the directed pathway leading to ortho-to-fluorine selectivity. In contrast, for the Ir(iii)/dtbpy catalytic system, the directed pathway is 1.2 kcal mol−1 more favoured over the undirected pathway bringing about ortho-to-silyl selectivity. For Co(i)/iPrPNP catalyzed borylation, the undirected pathway which involves steps of ortho-to-fluorine C–H oxidative addition, C–B reductive elimination, B–B oxidative addition, and B–H reductive elimination is favorable due to the electron deficient character of the ortho-to-fluorine C–H bond. For Ir(iii)/dtbpy catalyzed borylation, the directed pathway consisting of Si–H oxidative addition, B–H reductive elimination, C–H oxidative addition, B–B oxidative addition, C–B reductive elimination, Si–H reductive elimination is favored over the undirected pathway attributed to the directing effect of the hydrosilyl group. The favourable undirected pathway (ortho-to-fluorine selectivity) for Co(i)/iPrPNP catalyzed borylation and the favourable directed pathway (ortho-to-silyl selectivity) for Ir(iii)/dtbpy catalyzed borylation could explain well the experimentally observed ortho-to-fluorine borylation of hydrosilyl substituted fluoroarenes with cobalt catalyst  and ortho-to-silyl selectivity with iridium catalyst .In this work, density functional theory (DFT) calculations are performed to understand the origin of the regioselective C–H borylation of aromatics catalyzed by Co( i)/iPrPNP and Ir(iii)/dtbpy .In this work, density functional theory (DFT) calculations are performed to understand the origin of the regioselective C–H borylation of aromatics catalyzed by Co( Generally, strategies for the regioselective C–H borylation of aromatics include the undirected reaction pathway, in which no directing groups are involved in the reaction,3 and directing group controlled regioselective borylation,3 where the reaction regioselectivity is well controlled by a directing group.Transition metal catalyzed C–H borylation of aromatics has attracted considerable attention as it offers an alternative method to standard organic synthesis.ortho-to-fluorine selectivity was controlled by steric hindrance in iridium/dtbpy catalyzed borylation of trisubstituted fluoroarenes4  on the substrate is an effective way to achieve meta/para-to-fluorine C–H borylation.8–10 The interactions between directing groups and catalyst could bring one of the ortho-C–H bonds close to the metal center and promote its regioselective activation.9 For example, Iwasawa reported the iridium-picolylamine catalyzed ortho-to-amine borylation of fluoroarenes using dimethylamine as the directing group8  while Sunoj's group reported the use of hydrosilyl (–SiR2H) as a directing group in the iridium-catalyzed regioselective borylation of the benzylic C–H bond.9 Although there have been some reports on the Si–Co and Si–Ir metal complex,3 and the directing effect of the silyl group has been identified in iridium catalyzed borylation of benzylic C–H bond,9 detailed mechanism study on the regioselectivity of the borylation reactions in The examples mentioned above clearly demonstrate that the C–H borylation of aromatics can proceed by the undirected or directed pathways with the iridium or cobalt-based catalysts.2pin2 as the model /dtbpy are calculated to make comparison and explain the regiochemical preference  and Ir(iii) catalyzed borylation reactions are cat1 and cat1′, respectively, we discuss all the reaction pathways in the following sections with cat1 and cat1′ as the starting points, given that a cascade of steps along the reaction pathways is triggered by the active catalysts.We choose the reaction between hydrosilyl substituted fluoroarenes and Bhe model . Activateference . Since tiii) and Co(i) catalyzed borylation of aromatics proposed in literature,12 the directing group controlled borylation catalyzed by iridium may proceed in a way that the iridium centre is brought close to the ortho-to-silyl C–H bond by the silyl group and induces the activation of ortho-to-silyl C–H bond to form a 5-membered cycle.12 In contrast, cobalt-catalyzed borylation starts with ortho-to-fluorine C–H oxidative addition13 and no participation of directing group. The adaption of reported mechanisms to our peculiar reaction system is shown in According to the probable mechanisms of Ir(i)/iPrPNP catalyzed directed and undirected pathways. The optimized structures of selected transition states (TS) and intermediates are given in i) species studied show the tridentate coordination of the pincer ligand. The Co–N distance of cobalt pincer-complex cat1 , and can be considered as the rate determining step. Starting from int9a, in place of B2Pin2 oxidative addition, HBpin is also possible to add to the cobalt center following with the C–B reductive elimination and regeneration of cat1. The corresponding energetic profile is shown in −1  and is the rate-determining step -catalyzed benzylic C–H borylation (−1) is too high to occur under the experimental condition . This calculation result is different from the hydrosilyl directed borylation of ortho-hydrosilyl benzene in which the borylation of the benzylic C–H is favorable over the aromatic C–H bond activation.9Different from the directed pathway, the undirected pathway starts with the position . Then, ting step . The catrylation . As a re−1, TS4b in i)/iPrPNP system is much lower than that of the direct pathway /iPrPNP catalyzed borylation favors the undirect pathway. With Co(i)/iPrPNP catalytic system, the calculated favorable undirect pathway (ortho-to-fluorine selectivity) is well consistent with the experimental observed ortho-to-fluorine regioselectivity which is reported in the literature11  also well explains the relatively low chemical yield in the cobalt catalyzed model reaction (53%).12 It is worth noting that a recent computational study has revealed that the cobalt–carbon bonds of the intermediate in the (iPrPNP)Co-catalyzed borylation could be strengthened by the ortho-fluorine atom, which gives an additional demonstration of the ortho-to-fluorine regioselectivity other than para- or meta-selectivity.13Obviously, the overall barrier in the undirect pathway /iPrPNP, we turn to the similar pathways catalyzed by Ir(iii)/dtbpy catalytic system. The energy and geometric features of each elementary step involved in the Ir(iii)/dtbpy catalyzed directed and undirected pathways are shown in After a brief study on the directed and undirected pathways catalyzed by Co/dtbpy is lower than that catalyzed by Co(i)/iPrPNP  , the Mulliken charge on the cobalt center of TS2b is negative while that on iridium of TS2b′ is positive .It is worth noting that the barrier for the initial of TS2b′  (25.8 kc−1 (TS2a′). Given that the formed Int3a′ is saturated coordination,13 it is expected to exclude one molecular of HBpin prior to the C–H oxidative insertion. Upon release of one molecular HBpin, the following C–H oxidative insertion is accompanied by the release of another molecular HBpin which can be confirmed by IRC calculations. Then the intermediate Int8a′ is afforded, which has open coordination sites. One equivalent of B2pin2 thereafter oxidatively add to Int8a′, generating Int10a′viaTS9a′, with an overall barrier of 24.6 kcal mol−1. In the intermediate Int10a′, one boryl group is situated close to the ortho-to-silyl aromatic carbon  than other pathways  and should be finally ruled out. Similar to Co(i)-catalyzed benzylic C–H borylation, it is different from the hydrosilyl directed borylation of ortho-hydrosilyl benzene in which the borylation of the benzylic C–H bond is favorable over the borylation of the aromatic C–H bond.9 Comparing the rate-determining step in the directed path I′ and undirected path II′ for the iridium catalyzed C–H borylation (TS9a′vs.TS2b′), the directed pathway leading to ortho-to-silyl selectivity is 1.2 kcal mol−1 more favorable over undirected pathway leading to ortho-to-fluorine selectivity /dtbpy catalytic system, the calculated favorable directed pathway (ortho-to-silyl selectivity) is also consistent with experimental observed ortho-to-silyl selectivity11 /dtbpy and Co(i)/iPrPNP catalysts have been studied by DFT calculation. It shows that the borylation of hydrosilyl substituted fluoroarenes by Ir(iii)/dtbpy exhibits an ortho-to-hydrosilyl selectivity and follows a directed reaction pathway consisting of steps: (i) Si–H oxidative addition (ii) H–B reductive elimination, (iii) C–H bond oxidative addition and H–B reductive elimination, (iv) B–B oxidative addition, (v) C–B formation, (vi) H–B oxidative addition and (vi) Si–H reductive elimination. The preference for ortho-to-hydrosilyl selectivity in Ir(iii)/dtbpy catalyzed borylation can be attributed to the directing effect of hydrosilyl group. The borylation of hydrosilyl substituted fluoroarenes by Co(i)/iPrPNP, however, exhibits a high selectivity of ortho-to-fluorine and follows the undirected pathway which involving the steps: (i) C–H oxidative addition, (ii) C–B reductive elimination, (iii) B–B oxidative addition, and (iv) B–H reductive elimination. The preference for ortho-to-fluorine selectivity in Co(i)/iPrPNP catalyzed borylation is attributable to the acidity of ortho-to-fluorine C–H bond, while in the silyl-directed pathway, the high steric hindrance in the transition state of C–B reductive elimination leads to too high overall barrier to overcome. These calculation results well explain the experimental observation reported previously, strongly suggesting the accuracy of our calculation. The work present here therefore provides rational mechanistic insights into the origin of regioselective borylation of hydrosilyl substituted fluoroarenes. This will be helpful to well understand the underlying physics of the regioselective borylation of hydrosilyl substituted fluoroarenes and can be extended to the synthesis of other organic compounds with predictable regioselectivity by introducing suitable directing group, adjusting the available coordination sites on the catalyst, and/or modifying the electronic effects of the catalyst.The mechanisms of regioselective borylation of hydrosilyl substituted fluoroarenes by Ir19 basis for other atoms. Frequency results were examined to confirm stationary points as transition states (only one imaginary frequency) or minima (no imaginary frequencies), and were also used to obtain zero-point energy-corrected enthalpies and free energies at 298.15 K and 1 atm. In addition, intrinsic reaction coordinate (IRC) analysis was conducted to confirm that the transition state connects the correct reactant and product on the potential energy surface.20 The energetic results were further improved by single-point energy calculations at ωB97XD21/BSII level of theory, where BSII represents a basis set with SDD22 for Ir and Co and Def2TZVP21 basis set for other atoms. The solvent effects accounted by the SMD23 solvation model, using the experimental solvent tetrahydrofuran. Furthermore, natural population analysis (NPA)24 was performed at the same level by single point calculations. The Gibbs free energies obtained from the ωB97XD/BSII//B3LYP/BS1 level was discussed in this study, unless otherwise specified. All calculations are performed with the Gaussian 09 program package.25Geometry optimizations without symmetry restriction were carried out at the B3LYPThere are no conflicts to declare.RA-010-D0RA03428B-s001