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Enzyme replacement therapy: current challenges and drug delivery prospects via extracellular vesicles
No full textAdditive manufacturing as a tool for high-throughput experimentation
No full textAdditive manufacturing (AM) is a disruptive technology with a unique capability in fabricating parts with complex geometry and fixing broken supply chains. However, many AM techniques are complicated with their processing features due to complex heating and cooling cycles with the melting of feedstock materials. Therefore, it is quite challenging to directly apply the materials design and processing optimization method used for conventional manufacturing to AM techniques. In this viewpoint paper, we discuss some of the ongoing efforts of high-throughput (HT) experimentation, which can be used for materials development and processing design. Particularly, we focus on the beam- and powder-based AM techniques since these methods have demonstrated success in HT experimentation. In addition, we propose new opportunities to apply AM techniques as the materials informatic tools contributing to materials genome
Development and experimental verification of search and rescue ROV
No full textThis paper presents the design of a new type of search and rescue remotely operated vehicle (ROV) system. The goal is to achieve the underwater target search and detection and small target capture and rescue operation requirements. First, the overall design of the whole underwater surface system and the layout design of the propulsion system are given. On this basis, the ROV frame structure, electronic cabin, and power cabin are designed and analyzed. To accomplish the grasping task, a grasping hand is designed based on a multifunctional manipulator to achieve underwater grasping. To make the ROV more intelligent, different kinds of underwater object detection and tracking methods are adopted and analyzed. Finally, it was tested in a pool and the sea to verify the reliability and stability of the designed search and rescue ROV
Limitations of using simple indicators for evaluating agricultural emission reductions at farm level — evidence from Kenyan smallholder dairy production
No full textNational-scale carbon footprints of livestock production are commonly computed from a set of production system characteristics that serve as inputs for greenhouse gas (GHG) emission models. We evaluated the feasibility of using such equations at a finer scale to derive a simple farm-scale indicator of emission intensity (milk yield per head). Using probabilistic simulations, we quantified the impact of input variable uncertainty on emission estimates for smallholder dairy farms in Kenya. We simulated emissions for farm-scale scenarios generated from a survey of 414 households and published or expert-estimated uncertainty bounds. We simulated the impacts of five interventions: changing breeds, retiring unproductive males, keeping fewer replacement males, feeding forage supplements, and balancing animal diets. Impacts were assessed against a true counterfactual and against a more realistic scenario affected by random effects. We estimated errors incurred in classifying farms into adopters and non-adopters of the innovations based on changes in milk yield per animal. Given the current uncertainty, such classification would either miss a large percentage of adopters or misclassify many non-adopters as adopters. As a critical uncertainty, we identified the milk yield of dairy cows. Added precision on this metric reduced but did not eliminate classification errors. We remain cautiously optimistic about using milk yield per head to proxy emission intensity, but its effective use will require further reduction of critical uncertainties. Replacing generic recommendations of parameter uncertainties with context-specific error estimates might lead to a more efficient quantification of the carbon footprint of milk production on smallholder farms
Hard and soft tissue augmentation with occlusive titanium barriers in jaw vertical defects: a novel approach
No full textAim: The aim of this study was to evaluate hard and soft tissue changes following guided bone regeneration (GBR), with occlusive titanium barriers (OTB), in the rehabilitation of partially edentulous atrophic jaws. Vertical bone gain (VBG), horizontal bone width (HBW), and flap thickness (FT) changes, observed between the first and the second surgical stages, were evaluated.Methods: The study included 35 patients (9 men and 26 women; mean age 60 ± 10.53 years) in need of vertical bone augmentation for implant placement. Seventy implants were placed, 44 with a one-stage approach (Group A) and 26 with a two-stage approach (Group B). VBG, HBW, and FT were measured and statistically compared.Results: VBG for implants placed in Group B was significantly higher than those placed in Group A (P = 0.006). The increased HBW in Group B was highly significant compared to that exhibited in Group A (P = 0.000). A highly significant difference was found in FT before and after the GBR in the two groups considered together, for both the upper and lower jaws (P = 0.000 for both).Conclusions: OTBs are reliable devices in GBR, yielding predictable results in terms of bone augmentation. In almost all cases (94.3%), a spontaneous increase of the FT, at the second surgical phase, was observed. This could be due to the titanium surface features which increases spontaneously the thickness of soft tissues over the OTB
Female urethral stricture: techniques for reconstruction
No full textFemale urethral stricture (FUS) is a rare condition. It was not studied robustly for many years, but interest has grown recently in the reconstructive urology community, leading to an increase in publications. In this review, we gather the latest data regarding FUS and its different therapeutic options. Studies are summarized, split by technique. We also review the recently published European Guidelines. In addition, we share our preferred surgical technique and our views on future options. Diagnosing FUS can often be challenging and requires a high index of clinical suspicion. Its vague clinical symptoms and empiric initial treatments combine to make FUS an underdiagnosed condition. The lack of consensus on how to define FUS also compounds the problem. Appropriate diagnosis requires thorough investigation, and ancillary studies such as video urodynamics, cystoscopy, and voiding cystourethrogram may be useful. Treatment options range from conservative management to definitive procedures, although studies have shown that conservative measures such as urethral dilation have a low success rate overall. Within definitive management, augmented urethroplasty - using either flaps or grafts, has proven to be the gold standard. Both have shown excellent results over time; however, there is insufficient data available to recommend one over the other. Contemporary data has an overall poor level of evidence. Although challenging due to the rarity of the problem, a proper randomized controlled clinical trial comparing the principal surgical options and their outcomes would be beneficial and would allow for more informed decision making when considering options for women with urethral stricture
Parastomal hernia repair
No full textDespite significant advances in abdominal wall reconstruction, parastomal hernias remain a complex problem, with a high risk of recurrence following repair. While a number of surgical hernia repair techniques have been proposed, there is no consensus on optimal management. Several clinical variables must be considered when developing a comprehensive repair plan that minimizes the likelihood of hernia recurrence and surgical site occurrences. In this review, we describe the incidence of parastomal hernias and discuss pertinent risk factors, medical history findings, physical examination findings, supplementary diagnostic modalities, parastomal hernia classification systems, surgical indications, and repair techniques. Special consideration is given to the discussion of mesh reinforcement, including available biomaterials, anatomic plane selection, and the extent of mesh reinforcement. Although open repairs are the primary focus of this article, minimally invasive laparoscopic and robotic approaches are also briefly described. It is our hope that the provided surgical outcome data will help guide surgical management and optimize outcomes for affected patients
Tumor microenvironment and immunology of cholangiocarcinoma
No full textCholangiocarcinoma (CCA), an aggressive tumor originating from both intra- and extra-hepatic biliary cells, represents an unmet need in liver oncology, as treatment remains largely unsatisfactory. A typical feature of CCA is the presence of a complex tumor microenvironment (TME) composed of neoplastic cells, a rich inflammatory infiltrate, and cancer-associated fibroblasts and desmoplastic matrix that makes it extremely chemoresistant to traditional chemotherapeutic drugs. In this review, we describe the cell populations within the TME, in particular those involved in the innate and adaptive immune response and how they interact with tumor cells and with matrix proteins. The TME is crucial for CCA to mount an immune escape response and is the battlefield where molecularly targeted therapies and immune therapy, particularly in combination, may actually prove their therapeutic value
Liver cancer understaging in liver transplantation in the current era of radiologic imaging and newer generation locoregional therapies
No full textBackground: Discordance in hepatocellular carcinoma (HCC) staging between pre-transplant imaging and explant pathology is associated with an increased risk of recurrence and death. Our aim was to evaluate variables that predicted concordance/discordance in the era of new generation locoregional therapies (LRT) and improved radiologic technology in diagnosis. Methods: A single-center retrospective study was performed on patients who received a liver transplant for HCC between 2008-2019. Pre- and post-LT variables, including type of LRT, downstaging (DS), transplant time period, and radiologic response to LRT, were analyzed for concordance/discordance. Kaplan-Meier analysis was used to assess post-LT survival. Results: Of 146 patients transplanted within Milan Criteria (MC), discordance rates (understaged) were 45%. Discordance was associated with ≥ 3 HCC lesions at diagnosis but not newer generation LRT (transarterial radioembolization/ stereotactic body radiation therapy), traditional LRT or combination. No differences in discordance were seen between transplant periods (2008-2013 vs. 2014-2019), but those within MC in the earlier period had higher concordance rates. A trend was observed between DS and discordance. Conclusion: HCC stage discordance remains common and poorly predictable. Discordance was associated with three or more HCC lesions at the time of diagnosis. Patients within MC transplanted between 2008-2013 was associated with concordance, while a trend was noted between DS and discordance. No other pre- or post- LT variables predicted discordance/ concordance. Discordance was associated with decreased survival
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