Saccular and Fusiform Abdominal Aortic Aneurysms Treated With Endovascular Repair Differ in Presentation and Treatment Threshold: Analyses Using a National Clinical Database in Japan.

BACKGROUND: Saccular abdominal aortic aneurysms (AAAs) are considered to be at higher risk of rupture than fusiform AAAs, but not much is known about the extent of this risk. Therefore, this study aimed to compare the rupture presentation between fusiform and saccular AAAs. METHODS AND RESULTS: This is a retrospective cohort study on 27 290 patients who underwent primary endovascular repair for a degenerative AAA between 2016 and 2019, and who were registered in the National Clinical Database in Japan. At operation for nonruptured case, the aneurysm diameter was significantly smaller in saccular AAAs than in fusiform AAAs (median, 44.0 versus 51.0 mm; P<0.001). Similarly, aneurysm diameter at rupture was significantly smaller in saccular AAAs than in fusiform AAAs (median, 55.6 versus 68.0 mm; P<0.001). The likelihood of repair for rupture was significantly higher in saccular AAAs than in fusiform AAAs in the 40- to 54-mm diameter range, in which saccular morphology was found to be an independent risk factor for rupture against fusiform morphology by adjusting for sex and aneurysm diameter (odds ratio, 2.54 [95% CI, 1.75-3.69]). In addition, receiver-operating characteristic curve analysis revealed that the cutoff diameter to predict rupture was smaller in saccular AAAs than in fusiform AAAs (50.5 and 59.5 mm, respectively) based on the Youden index. CONCLUSIONS: Saccular AAAs presented at smaller diameters than fusiform AAAs in patients with ruptured AAAs treated with endovascular aortic repair, which supports the idea that saccular AAAs should be treated at smaller diameters.

How many people can the Qinghai-Tibet Plateau hold, and how large cities can be built in recent hundred years?

The Qinghai-Tibet Plateau (QTP) serves as a vital barrier for both national security and ecological preservation. Overpopulation and urban sprawl pose threats to its ecological security, while underpopulation and small urban cities also undermine national security. Hence, optimizing population distribution and urban development on the QTP is crucial for bolstering the national security perimeter and ensuring basic modernisation across China. Nonetheless, understanding the population carrying capacity (CC) of the QTP and how large cities can safeguard both national security and ecological stability remains limited. To address this research gap, we utilised various model algorithms and methodologies to assess the population CC and urban scale of the QTP from seven different perspectives. The results indicate that the permanent population CC of the QTP in 2050 will be 26.2 million people, with an urbanisation level of 57.25 %, thereby allowing 15 million people to enter cities. Thus, the QTP can add 13.07 million people to its permanent population in the future, with a newly added urban population of 8.75 million, increasing the urbanisation level by 9.67 %. The future permanent population will mainly be distributed in the Xining, Lhasa, and Qaidam metropolitan areas. Combined, the permanent and urban populations will account for 38.54 % and 49.84 % of the QTP, respectively. Moreover, these populations will be moderately dispersed in 11 important node cities and more widely dispersed in key border towns. These findings provide a scientific basis for the sustainable development and high-quality urbanisation of the QTP, which have important implications for achieving sustainable development goals, offering crucial references for governments to formulate resource management policies and achieve sustainable resource utilisation.

Size thresholds for repair of abdominal aortic aneurysms warrant reconsideration.

BACKGROUND: The historical size threshold for abdominal aortic aneurysm (AAA) repair is widely accepted to be 5.5 cm for men and 5.0 cm for women. However, contemporary AAA rupture risks may be lower than historical benchmarks, which has implications for when AAAs should be repaired. Our objective was to use contemporary AAA rupture rates to inform optimal size thresholds for AAA repair. METHODS: We used a Markov chain analysis to estimate life expectancy for patients with AAA. The primary outcome was AAA-related mortality. We estimated survival using Social Security Administration life tables and published contemporary AAA rupture estimates. For those undergoing repair, we modified survival estimates using data from the Vascular Quality Initiative and Medicare on complications, late rupture, and open conversion. We used this model to estimate the AAA repair size threshold that minimizes AAA-related mortality for 60-year-old average-health men and women. We performed a sensitivity analysis of poor-health patients and 70- and 80-year-old base cases. RESULTS: The annual risk of all-cause mortality under surveillance for a 60-year-old woman presenting with a 5.0 cm AAA using repair thresholds of 5.5 cm, 6.0 cm, 6.5 cm, and 7.0 cm was 1.7%, 2.3%, 2.7%, and 2.8%, respectively. The corresponding risk for a man was 2.3%, 2.9%, 3.3%, and 3.4% for the same repair thresholds, respectively. For a 60-year-old average-health woman, an AAA repair size of 6.1 cm was the optimal threshold to minimize AAA-related mortality. Life expectancy varied by <2 months for repair at sizes from 5.7 cm to 7.1 cm. For a 60-year-old average-health man, an AAA repair size of 6.9 cm was the optimal threshold to minimize AAA-related mortality. Life expectancy varied by <2 months for repair at sizes from 6.0 cm to 7.4 cm. Women in poor health, at various age strata, had optimal AAA repair size thresholds that were >6.5 cm, whereas men in poor health, at all ages, had optimal repair size thresholds that were >8.0 cm. CONCLUSIONS: The optimal threshold for AAA repair is more nuanced than a discrete size. Specifically, there appears to be a range of AAA sizes for which repair is reasonable to minmized AAA-related mortality. Notably, they all are greater than current guideline recommendations. These findings would suggest that contemporary AAA size thresholds for repair should be reconsidered.

Monitoring of Visible Particles in Parenteral Products by Manual Visual Inspection-Reassessing Size Threshold and Other Particle Characteristics that Define Particle Visibility.

Visible particles are a critical quality attribute for parenteral products and must be monitored. A carefully designed, executed, and controlled drug product manufacturing process including a final 100 % visual inspection and appropriate end-product controls ensures that visible particles are consistently minimized and demonstrates that the injectable DP is practically free from visible particles. Visual inspection, albeit appearing as a simple analytical procedure, requires several technical and operational controls to ensure adequate performance. To gather new data on particle visibility and shed light on this decade-old challenge, a multi-company blinded visual inspection threshold study was conducted. A major goal of the study was visual assessment of several particle types of different sizes in small volume vials, as a challenging configuration for visual inspection, across 9 biopharmaceutical companies in order to determine the visibility limit. The study results provide key insights into limitations and challenges of visual inspection, namely, no universal visibility limit can be applied to all particle types as the detectability varies with particle type, number, and size. The study findings underscore the necessity of setting realistic expectations on size-based visibility limits in visual inspection, robust procedures for analyst training and qualification, and harmonization of guidelines globally.

Size-Dependent In Vivo Transport of Nanoparticles: Implications for Delivery, Targeting, and Clearance.

Understanding the in vivo transport of nanoparticles provides guidelines for designing nanomedicines with higher efficacy and fewer side effects. Among many factors, the size of nanoparticles plays a key role in controlling their in vivo transport behaviors due to the existence of various physiological size thresholds within the body and size-dependent nano-bio interactions. Encouraged by the evolving discoveries of nanoparticle-size-dependent biological effects, we believe that it is necessary to systematically summarize the size-scaling laws of nanoparticle transport in vivo. In this review, we summarized the size effect of nanoparticles on their in vivo transport along their journey in the body: begin with the administration of nanoparticles via different delivery routes, followed by the targeting of nanoparticles to intended tissues including tumors and other organs, and eventually clearance of nanoparticles through the liver or kidneys. We outlined the tools for investigating the in vivo transport of nanoparticles as well. Finally, we discussed how we may leverage the size-dependent transport to tackle some of the key challenges in nanomedicine translation and also raised important size-related questions that remain to be answered in the future.

Prediction of post-Darcy flow based on the spatial non-local distribution of hydraulic gradient: Preliminary assessment of wastewater management.

Understanding high-velocity pollutant transport dependent on the large hydraulic gradient and/or heterogeneity of the aquifer and criteria for the onset of post-Darcy flow have attracted considerable attention in water resources and environmental engineering applications. In this study, a parameterized model is established based on the equivalent hydraulic gradient (EHG) which affected by spatial nonlocality of nonlinear head distribution due to the inhomogeneity at a wide range of scales. Two parameters relevant to the spatially non-local effect were selected to predict the development of post-Darcy flow. Over 510 sets of laboratory one-dimensional (1-D) steady hydraulic experimental data were used to validate the performance of this parameterized EHG model. The results show that (1) the spatial nonlocal effect of the whole upstream is related to the mean grain size of the medium, and the anomalous variation due to the small grain size implies the existence of the particle size threshold. (2) The parameterized EHG model can effectively capture the nonlinear trend that fails to be described by the traditional local form of nonlinear models, even if the specific discharge stabilizes at the later stages. (3) The Sub-Darcy flow distinguished by the parameterized EHG model can be equated to the post-Darcy flow, and then the criteria for the post-Darcy flow will be strictly distinguished under the premise of determining the hydraulic conductivity. The results of this study facilitate the identification and prediction of high-velocity non-Darcian flow in wastewater management and provide insight into mass transport by advection at the fine-scale.

Introducing an Evidence-Based Approach to Wait-And-Scan Management of Sporadic Vestibular Schwannoma: Size Threshold Surveillance.

The advent of MRI has led to more sporadic vestibular schwannomas diagnosed today than ever before. Despite the average patient being diagnosed in their sixth decade of life with a small tumor and minimal symptoms, population-based data demonstrate that more tumors per capita are treated today than ever before. Emerging natural history data justify either an upfront treatment approach or the "Size Threshold Surveillance" approach. Specifically, if the patient elects to pursue observation, then existing data support the tolerance of some growth during observation in appropriately selected patients up until a specific size threshold range (about 15 mm of CPA extension). The current article discusses the rationale behind a shift in the existing observation management approach, where initial detection of growth typically begets treatment, and outlines the application of a more flexible and nuanced approach based on existing evidence.

Defining clinically significant tumor size in vestibular schwannoma to inform timing of microsurgery during wait-and-scan management: moving beyond minimum detectable growth.

OBJECTIVE: Detection of vestibular schwannoma (VS) growth during observation leads to definitive treatment at most centers globally. Although ≥ 2 mm represents an established benchmark of tumor growth on serial MRI studies, 2 mm of linear tumor growth is unlikely to significantly alter microsurgical outcomes. The objective of the current work was to ascertain where the magnitude of change in clinical outcome is the greatest based on size. METHODS: A single-institution retrospective review of a consecutive series of patients with sporadic VS who underwent microsurgical resection between January 2000 and May 2020 was performed. Preoperative tumor size cutpoints were defined in 1-mm increments and used to identify optimal size thresholds for three primary outcomes: 1) the ability to achieve gross-total resection (GTR); 2) maintenance of normal House-Brackmann (HB) grade I facial nerve function; and 3) preservation of serviceable hearing (American Academy of Otolaryngology-Head and Neck Surgery class A/B). Optimal size thresholds were obtained by maximizing c-indices from logistic regression models. RESULTS: Of 603 patients meeting inclusion criteria, 502 (83%) had tumors with cerebellopontine angle (CPA) extension. CPA tumor size was significantly associated with achieving GTR, postoperative HB grade I facial nerve function, and maintenance of serviceable hearing (all p < 0.001). The optimal tumor size threshold to distinguish between GTR and less than GTR was 17 mm of CPA extension (c-index 0.73). In the immediate postoperative period, the size threshold between HB grade I and HB grade > I was 17 mm of CPA extension (c-index 0.65). At the most recent evaluation, the size threshold between HB grade I and HB grade > I was 23 mm (c-index 0.68) and between class A/B and C/D hearing was 18 mm (c-index 0.68). Tumors within 3 mm of the 17-mm CPA threshold displayed similarly strong c-indices. Among purely intracanalicular tumors, linear size was not found to portend worse outcomes for all measures. CONCLUSIONS: The probability of incurring less optimal microsurgical outcomes begins to significantly increase at 14-20 mm of CPA extension. Although many factors ultimately influence decision-making, when considering timing of microsurgical resection, using a size threshold range as depicted in this study offers an evidence-based approach that moves beyond reflexively recommending treatment for all tumors after detecting ≥ 2 mm of tumor growth on serial MRI studies.

Increasing feed intake in domestic goats (Capra hircus): Measured effects on chewing intensity are probably driven by escape of few, large particles from the forestomach.

On the one hand, oral processing - mastication - is considered a relatively inflexible component of mammalian feed acquisition that constrains instantaneous intake rates. On the other hand, experimental data shows that the level of feed intake affects faecal particle size and hence net chewing efficiency in ruminants, with larger particles occurring in the faeces at higher intakes. Here, we report the effect of an increased feed intake during maintenance (L1), late (200% of L1) and peak lactation (300% of L1) of a consistent diet (hay:concentrates 50:50) in eight domestic goats on various measures of digestive physiology including faecal mean particle size (MPS). Increasing intake led to an increased gut fill, a reduction in digesta retention times, and an increase in faecal MPS (from 0.57 to 0.72 mm). However, this was an effect of the large particle fraction (>2 mm) being disproportionately excreted at higher intakes; if MPS was assessed on the basis of particles below the typical escape threshold (≤1 mm), there was no difference between intake levels. These findings suggest that the effect of intake on the calculated net chewing efficiency in ruminants may rather be an effect of increased large particle escape from the forestomach than a reduced chewing intensity per bolus during ingestion or rumination.

Exploration and insights into the cellular internalization and intracellular fate of amphiphilic polymeric nanocarriers.

The beneficial or deleterious effects of nanomedicines emerge from their complex interactions with intracellular pathways and their subcellular fate. Moreover, the dynamic nature of plasma membrane accounts for the movement of these nanocarriers within the cell towards different organelles thereby not only influencing their pharmacokinetic and pharmacodynamic properties but also bioavailability, therapeutic efficacy and toxicity. Therefore, an in-depth understanding of underlying parameters controlling nanocarrier endocytosis and intracellular fate is essential. In order to direct nanoparticles towards specific sub-cellular organelles the physicochemical attributes of nanocarriers can be manipulated. These include particle size, shape and surface charge/chemistry. Restricting the particle size of nanocarriers below 200 nm contributes to internalization via clathrin and caveolae mediated pathways. Similarly, a moderate negative surface potential confers endolysosomal escape and targeting towards mitochondria, endoplasmic reticulum (ER) and Golgi. This review aims to provide an insight into these physicochemical attributes of nanocarriers fabricated using amphiphilic graft copolymers affecting cellular internalization. Fundamental principles understood from experimental studies have been extrapolated to draw a general conclusion for the designing of optimized nanoparticulate drug delivery systems and enhanced intracellular uptake via specific endocytic pathway.

Concordance of Three International Guidelines for Thyroid Nodules Classified by Ultrasonography and Diagnostic Performance of Biopsy Criteria.

OBJECTIVE: To investigate the concordance of three international guidelines: the Korean Thyroid Association/Korean Society of Thyroid Radiology, American Thyroid Association, and American College of Radiology for thyroid nodules classified by ultrasonography (US) and the diagnostic performance of simulated size criteria for malignant biopsies. MATERIALS AND METHODS: A total of 2586 thyroid nodules (≥ 1 cm) were collected from two multicenter study datasets. The classifications of the thyroid nodules were based on three different guidelines according to US categories for malignancy risk, and the concordance rate between the different guidelines was calculated for the classified nodules. In addition, the diagnostic performance of criteria related to four different simulated biopsy sizes was evaluated. RESULTS: The concordance rate of nodules classified as high- or intermediate-suspicion was high (84.1-100%), but low-suspicion or mildly-suspicious nodules exhibited relatively low concordance (63.8-83.8%) between the three guidelines. The differences in sensitivity, specificity, and accuracy between the guidelines were 0.7-19.8%, 0-40.9%, and 0.1-30.5%, respectively, when the original biopsy criteria were applied. The differences decreased to 0-5.9%, 0-10.9%, and 0.1-8.2%, respectively, when simulated, similar biopsy size criteria were applied. The unnecessary biopsy rate calculated with the original criteria (0-33.8%), decreased with the simulated biopsy size criteria (0-8.7%). CONCLUSION: We found a high concordance between the three guidelines for high- or intermediate-suspicion nodules, and the diagnostic performance of the biopsy criteria was approximately equivalent for each simulated size criterion. The difference in diagnostic performance between the three guidelines is mostly influenced by the various size thresholds for biopsies.

Size threshold for follow-up of postmenopausal adnexal cysts: 1 cm versus 3 cm.

OBJECTIVES: To assess 3 cm size threshold for follow-up of simple cysts in postmenopausal women. MATERIALS AND METHODS: Radiology information system was retrospectively queried for "US pelvis complete" over 8 years in women > 50 years, with keywords ovarian cyst, adnexal cyst, ovarian mass, cystic mass, cystic neoplasm, ovarian neoplasm, and ovarian mass. Premenopausal women were excluded. Cysts, were classified as ≤ 1 cm, 1-3 cm, 3-5 cm, and ≥ 7 cm. Largest cysts on each ovary was recorded. EMR and imaging archives were reviewed for assessing size, stability duration, and surgical records. Descriptive statistics and confidence interval were performed. RESULTS: 4388 patients met the initial search criteria. 919 cysts in 896 women (age: 50-91 years, mean: 61.5 years) were identified. We found 162 cysts ≤ 1 cm, 352 1-3 cm, 296 3-7 cm , and 51 ≥ 7 cm cysts. 127 patients with 1-3 cm cysts had no follow-up. Final analysis of 225 1-3 cm cysts included 203 ovarian and 22 paraovarian cysts (average size = 1.95 cm (1.1-3.0 cm)). 103 ovarian cysts had less than 2 years, and 100 cysts had more than 2 years follow-up. All except one ovarian cyst were stable for the entire duration of their follow-up (Mean duration of follow-up 5.4 years) (0.3%, 95% CI 0.0-0.05). 40 cysts resolved. One simple cyst increased in size (followed over 3.25 years) without suspicious imaging features and benign on surgery. CONCLUSION: 1-3 cm cysts represented the most common size range (> 40%) in postmenopausal women, majority of which are stable over follow-up with benign outcome. 3 cm size threshold is appropriate for simple cyst follow-up in postmenopausal women.

Concordance of Three International Guidelines for Thyroid Nodules Classified by Ultrasonography and Diagnostic Performance of Biopsy Criteria

Evidence for a white matter lesion size threshold to support the diagnosis of relapsing remitting multiple sclerosis.

BACKGROUND: The number of white matter lesions (WML) in brain MRI is the most established paraclinical tool to support the diagnosis of multiple sclerosis (MS) and to monitor its course. Diagnostic criteria have stipulated a minimum detectable diameter of 3 mm per WML, although this threshold is not evidence-based. We aimed to provide a rationale for a WML size threshold for three-dimensional MRI sequences at 3 T by comparing patients with relapsing-remitting MS (RRMS) to control subjects (CS). METHODS: We analyzed MR images from two cohorts, obtained at scanners from two different vendors, each comprising patients with RRMS and CS. Both cohorts were examined with FLAIR and T1w sequences. In total, 232 patients with RRMS (Expanded Disability Status Scale: mean = 1.6 ± 1.2; age: mean = 36 ± 10) as well as 116 age- and sex-matched CS were studied. We calculated odds ratios across WML volumes. The WML size threshold, which discriminated best between patients and CS, was estimated with receiver operating characteristic curve analysis. RESULTS: In both cohorts, odds ratios increased continuously with increasing WML volumes, and discriminative power was highest at a WML size threshold corresponding to a diameter of about 3 mm. CONCLUSION: The stipulated WML size threshold of 3 mm in diameter for the diagnostic criteria of MS seems a reasonable choice for three-dimensional MRI sequences at 3 T.

Evidence for Male Horn Dimorphism and Related Pronotal Shape Variation in Copris lunaris (Linnaeus, 1758) (Coleoptera: Scarabaeidae, Coprini).

Male horn dimorphism is a rather common phenomenon in dung beetles, where some adult individuals have well-developed head horns (i.e., major males), while others exhibit diminished horn length (i.e., minor males). We focused on horn dimorphism and associated head and pronotum shape variations in Copris lunaris. We examined the allometric relationship between horn length (i.e., cephalic and pronotal horns) and maximum pronotum width (as index of body size) by fitting linear and sigmoidal models for both sexes. We then asked whether head and pronotum shape variations, quantified using the geometric morphometric approach, contributed to this allometric pattern. We found that female cephalic and pronotal horn growth showed a typical isometric scaling with body size. Horn length in males, however, exhibited sigmoidal allometry, where a certain threshold in body size separated males into two distinct morphs as majors and minors. Interestingly, we highlighted the same allometric patterns (i.e., isometric vs. sigmoidal models) by scaling horn lengths with pronotum shape, making evident that male horn dimorphism is not only a matter of body size. Furthermore, the analysis of shape showed that the three morphs had similar heads, but different pronota, major males showing a more expanded, rounded pronotum than minor males and females. These morphological differences in C. lunaris can ultimately have important functional consequences in the ecology of this species, which should be explored in future work.

Late mortality in females after endovascular aneurysm repair.

BACKGROUND: Abdominal aortic aneurysm (AAA) rupture is an adverse arterial remodeling event with high mortality risk. Because females have increased rupture risk with smaller AAAs (<5.5 cm), many recommend elective repair before the AAA reaches 5.5 cm. Elective repair improves survival for large AAAs, but long-term benefits of endovascular aneurysm repair (EVAR) for small AAAs in females remain less understood. The objective of this study was to identify if differences in late mortality exist between females undergoing elective EVAR at our institution for small and/or slow-growing AAAs compared with those who meet standard criteria. METHODS: We retrospectively analyzed all patients that underwent EVAR for infrarenal AAA from June, 2009-June, 2013. We excluded patients that were male, treated emergently or for iliac artery aneurysm, and that received renal and/or mesenteric artery stenting. Patients did not meet anatomic criteria if preoperative AAA diameter was <5.5 cm or enlarged <0.5 cm over 6 mo. Late mortality was assessed from the social security death index. RESULTS: Thirty-six of 162 elective EVAR patients (22.2%) were female (mean follow-up, 37.2 mo). Twenty patients (55.6%) met AAA size and/or growth criteria, whereas 16 (44.4%) did not meet criteria. Despite comparable demographics, comorbidities, and complications, patients that did not meet criteria had higher late mortality (37.5% versus 5%; P = 0.03) with a trend toward increased reoperation rate (25% versus. 5%; P = 0.48). Meeting size and/or growth criteria decreased odds of late death (odds ratio, 0.09; 95% confidence intervals, 0.01-0.83). CONCLUSIONS: There is increased late mortality in females receiving elective EVAR at our institution for small and/or slow-growing AAAs. This late mortality may limit the benefits of EVAR for this population.