Oiling-Out: Insights from Gibbsian Surface Thermodynamics by Stability Analysis.

The crystallization process is a significant stage in the pharmaceutical industry. During the process of crystallization with cooling, it is possible for a secondary liquid phase to appear before the formation of crystals. This phenomenon is called "oiling out" or liquid-liquid phase separation (LLPS). In this article, we explore the oiling-out phenomenon in a binary system of water and vanillin using stability analysis based on Gibbsian surface thermodynamics. To obtain the full picture of oiling out, we investigated three cases: droplet-solute-lean liquid equilibrium (DLE), crystal-solute-rich liquid equilibrium (CL'E), and crystal-solute-lean liquid equilibrium (CLE). The phase diagram of the system is plotted using the NRTL model for activity coefficients, along with considering the effect of the interfacial curvature on the phase diagram. From the phase boundaries and free-energy diagram of each case, we showed that the occurrence of the oiling-out phenomenon is justified based on the lower energy barrier of the droplet formation compared to that of the crystal formation. However, the energy level of a stable crystal is significantly lower and hence more stable than that of a stable droplet. Finally, we have determined different regions for droplet and crystal formation in the metastable phase diagram based on their supersaturation and provide insight for the oiling-out phenomenon.

An in-depth investigation of the impact of salt nature on the formulation of microemulsion systems.

Electrolytes have a wide range of technological applications. Despite the recent improvements in characterizing and predicting the phase behavior of microemulsion systems by hydrophilic-lipophilic deviation (HLD) and net-average curvature (NAC) frameworks, they are ineffective in the presence of different salts. This work seeks to bridge this gap by investigating the influence of salt nature on the microemulsion phase formulation. First, a one-dimensional salinity scan on different microemulsion systems consisting of sodium dodecyl benzene sulfonate as a surfactant, hexane as an oil and, several brines was carried out, and the effect of each salt on the phase behavior were precisely evaluated. The results for optimum salinity and solubilization parameter of different salts were consistent with the Hofmeister series. In addition, multiple linear regression model is presented to accurately predicting the optimum salinity of different salts using this research data and all the available experimental data. The results revealed that the values estimated by this model is in significant consistency with the experimental data by correlation coefficient of 0.92. Finally, the effect of salt type on the NAC parameters (length parameter, and characteristic length[Formula: see text] were evaluated to improve the predicting ability of this equation of state in the presence of various salts. We found that salt nature has a significant impact on both these parameters. It was found that the length parameter is linearly dependent on the optimum ionic strength of salts while the salting-out capacity of each salt was predominant factor affecting the characteristic length.

Prevention of radiotherapy-related oral mucositis with zinc and polyherbal mouthwash: a double-blind, randomized clinical trial.

BACKGROUND: A significant percentage of head and neck cancer (HNCs) patients receiving RT experience oral mucositis (OM). This study aimed to evaluate the effect of the polyherbal (containing chamomile, peppermint oil, Aloe vera, and honey) and zinc mouthwashes in comparison to the control (chlorhexidine) and placebo groups for prevention of radiation-induced OM. METHODS: This study was a double-blinded randomized clinical trial, conducted on 67 patients with HNCs undergoing radiotherapy. The eligible participants were randomized to receive either one of the following; zinc sulfate, polyherbal, chlorhexidine (Vi-one 0.2% CHX), or placebo mouthwash for 6 weeks. Follow-up evaluation of oral hygiene and the checklists of OM and the intensity of pain were filled out according to WHO assessment tool, Oral Mucositis Assessment Scale (OMAS), and Visual Analog Scale (VAS) in all the participants weekly for seven consecutive weeks. RESULTS: The results of present clinical trial demonstrated that the use of either zinc sulfate or polyherbal mouthwash significantly reduced the scores of OM and the severity of pain during weeks 2 to 7 after consumption compared with the CHX or placebo mouthwashes (P < 0.05). According to the post hoc analysis and compared with the placebo, a significantly better result was reported for zinc sulfate and polyherbal mouthwashes at weeks 2 to 7, but not for the CHX mouthwash. CONCLUSION: This study showed that the use of zinc sulfate or polyherbal mouthwashes is effective in prevention of both OM severity scores and pain related to OM intensity at weeks 2 to 7 following consumption in HNCs patients. Trial registration IRCT20190123042475N1 and IRCT20190123042475N2. Registration date: 2019-06-09, 2019-07-26.

Social, Environmental and Economic Impact Assessment of COVID-19 on Rural Tourism.

Today, various solutions have been proposed to improve the economic situation of villages and deprived areas, among which tourism is known as the best solution for those areas with the necessary potentials for tourism development. On other hand, the COVID-19 pandemic had significant effects on human life worldwide. The prevalence of COVID-19 has caused a lot of damage to different sectors of the global economy, but without a doubt, the rural tourism industry should be considered among the economic activities that have suffered the most from this virus. In this study, with the aim of investigating these effects on the rural tourism industry, it has been analyzed and compared in three important economic, social and environmental dimensions before and after the outbreak of the COVID-19. This quantitative study was used survey method. The statistical population of the study consisted of local stakeholders of rural tourism and experts of the relevant organizations in Natanz county of Iran. The results of confirmatory factor analysis indicate that the constructs used in the model have appropriate and acceptable fit. The results of the study also, showed that the prevalence of COVID-19 has adverse consequences including reducing the desirable economic and social effects of tourism mentioned among both groups of experts and rural stakeholders. from rural tourism stakeholders' opinion, environmental variables of the tourism areas before and after the COVID-19 was different, and in the absence of tourists in this area, the destructive environmental effects have strongly decreased.

Design of industrial wastewater demulsifier by HLD-NAC model.

The chemical method is one of the treatment techniques for the separation of oil-water emulsion systems. The selection of appropriate demulsifiers for each emulsion system is the most challenging issue. Hydrophilic-lipophilic-deviation (HLD) is a powerful semi-empirical model, providing predictive tools to formulate the emulsion and microemulsion systems. This work aims to apply HLD to obtain an optimal condition for demulsification of oil-in-water emulsion system-real industrial wastewater-with different water in oil ratios (WOR). Therefore, the oil parameter of the contaminant oil and surfactant parameter for three types of commercial surfactants were calculated by performing salinity scans. Furthermore, the net-average-curvature (NAC) framework coupled with HLD was used to predict the phase behavior of the synthetic microemulsion systems, incorporating solubilization properties, the shape of droplets, and quality of optimum formulation. The geometrical sizes of non-spherical droplets (Ld, Rd)-as an indicator of how droplet sizes are changing with HLD-were consistent with the separation results. Correlating Ld/Rd at phase transition points with bottle test results validates the hypothesis that NAC-predicted geometries and demulsification behavior are interconnected. Finally, the effect of sec-butanol was examined on both synthetic and real systems, providing reliable insights in terms of the effect of alcohol for WOR ≠ 1.

Intention to quit water pipe smoking among Iranian women: a qualitative directed content analysis.

BACKGROUND: Water-pipe smoking is the most common type of tobacco used among Iranian women. The aim of this study was to explain women's perceptions of their intention for quitting water-pipe smoking based on the theory of planned behavior. METHODS: The study was a qualitative content analysis which was carried out over 4 months in 2016 in Tehran-Iran. The participants were 26 women ages 18 to 45-years-old who smoked water-pipe and were selected through snowball sampling. The study was performed in hookah cafes, parks, and homes. The data were collected through individual interviews. The interviews were open-ended questions based on the theory of planned behavior. Directed content analysis was used to analyze the data. RESULTS: Findings showed that women did not intend to quit water-pipe in that time. Main contributing factors influencing not having intention of cessation were positive attitude and false beliefs toward hookah smoking, as well as having peers and family members who smoked water-pipe or approved its use. Although most females realized the obstacles associated with hookah cessation, they believed that quitting water-pipe smoking was up to them and could control more barriers. CONCLUSION: Social pressure, positive attitude and false beliefs towards hookah smoking, as well as external and internal obstacles diminished women 's intention for cessation. Therefore, it is recommended to apply the theory of planned behavior into behavior change interventions in order to increase the intention to quit water-pipe smoking.

Sonophotocatalytic treatment of AB113 dye and real textile wastewater using ZnO/persulfate: Modeling by response surface methodology and artificial neural network.

The present study investigates the synergistic performance of the sonophotolytic-activated ZnO/persulfate (US/UV/ZnO/PS) process in the decolorization of acid blue 113 (AB113) dye from aqueous solution and its feasibility for the treatment of real textile wastewater. Decolorization of AB113 solution was modeled by central composite design-response surface methodology (CCD-RSM) and artificial neural network (ANN) approaches and optimized by CCD-RSM and genetic algorithm (GA) approaches. Statistical metrics indicated that both CCD-RSM and ANN approaches seemed satisfactory. However, the results of statistical fit measures indicated a relative superiority of CCD-RSM as compared to the ANN approach. The results of optimization of the process parameters by CCD-RSM and GA approaches appeared to be similar as follows: pH = 6.1, reaction time = 25 min, US power density = 300 W/L, ZnO = 0.88 g/L and PS = 2.43 mmol/L. The synergistic effect of the hybrid US/UV/ZnO/PS process in comparison with its individual processes (US, UV, ZnO, and PS) was found to be 54.3%. Quenching experiments discovered that and HO are the main oxidizing radicals in a mildly acidic condition of the reaction solution. The removal efficiency of AB113 in the presence of some anions decreased in the order of bicarbonate > sulfate > phosphate > nitrate > chloride. Further, the reusability feasibility of ZnO showed that the ZnO material retained its photocatalytic property after five successive cycles of reusability test, while Zn2+ ion concentration in the reaction solution was measured to be 2.81 mg/L. The findings also indicated that the integrated process application suppresses extremely chemical and electrical costs. The study of the feasibility of the US/UV/ZnO/PS process in the treatment of real textile wastewater was done by determining COD, TOC and BOD5/COD ratio. Results demonstrated that the 96.6 and 97.1% reduction of COD and TOC was achieved after 5 and 7 h reaction time, respectively. The obtained BOD5/COD ratio changed from about 0.15 (for non-treated wastewater) to about 0.61 with increasing reaction time from zero to 90 min. In conclusion, the hybrid US/UV/ZnO/PS system can be proposed as a novel and promising approach to be utilized as a pretreatment technique before a biological treatment process to facilitate the biological treatment of recalcitrant textile wastewater.

Retinal Nerve Fiber Layer Thickness and Total Macular Volume in Multiple Sclerosis Subtypes and Their Relationship with Severity of Disease, a Cross-Sectional Study.

BACKGROUND: Optic neuritis (ON) is an inflammatory demyelinating lesion in the optic nerve, which is strongly associated with multiple sclerosis (MS). Optical coherence tomography (OCT) is a noninvasive technique for the evaluation of the retinal layers. Our aim was to examine OCT metrics including retinal nerve fiber layer thickness (RNFLT), and total macular volume (TMV), in MS subtypes and their relationship with duration, first manifestation, and severity of disease. MATERIAL AND METHODS: In this cross-sectional study, patients with a definite diagnosis of MS underwent complete ophthalmic and neurologic examination. OCT parameters including TMV and RNFLT were compared between MS subtypes and different first manifestations of MS. Their relationships were also studied with the duration and severity of disease based on the Expanded Disability Status Scale (EDSS) score. RESULTS: A total of 240 eyes were examined in 120 enrolled MS patients. The differences in RNFLT were not analytically meaningful between the subtypes of MS, but the differences in TMV values were statistically significant between the subtypes of MS (P: 0.39 and P: 0.04, respectively). The differences between RNFLT and TMV of eyes with and without ON were statistically significant between these two groups (P<0.001 and P<0.001). There was also an inverse correlation between EDSS disability score and RNFLT and TMV values (P: 0.00, r: -0.33 and P: 0.034, r: -0.11, respectively) and a significant inverse correlation between the duration of MS and RNFLT (P: 0.00, r: -0.47). The differences in RNFLT and TMV values were analytically meaningful between the categories of first manifestations of MS (P: 0.000 and P: 0.027, respectively). CONCLUSION: RNFLT and TMV represent noninvasive parameters for assessment of neuroaxonal degeneration in the anterior visual pathway that correlate with the severity and duration of multiple sclerosis. The lowest RNFLT and TMV values were also seen in the perceptual category between the first manifestations of MS. Therefore, they may be useful in the evaluation of MS patients.

Impacts of drought phenomenon on the chemical quality of groundwater resources in the central part of Iran-application of GIS technique.

In the recent decades, global warming has caused water shortages all over the world. This study aimed to investigate the impacts of drought caused by climate change on the chemical quality of groundwater in Saveh County, Markazi province, Iran. The physicochemical parameters of 29 wells were analyzed by the Standardized Precipitation Index (SPI) during the drought period 2004-2015. Wilcox and Schoeller diagrams were applied to evaluate the water quality of wells for irrigation and drinking purposes, respectively. Schoeller diagram was consulted to show the relative concentrations of anions and cations typically expressed in milliequivalents per liter. Also, the Wilcox diagram was consulted to determine the suitability of water for agriculture purposes. Finally, the geographic information system was applied to the zoning of the groundwater quality parameters. According to the results, almost 90% of wells were in the category of "very salty and harmful for agriculture uses" in the last year of the study period (2015). The Schoeller diagram suggests that the water quality of 72.5, 10.4, 65.5, 100, 44.9, and 69% of wells were inappropriate and exceeded the Iranian National Standard level, in terms of TDS, TH, Na+، Mg2+, Cl-, and SO42- in 2015, respectively. A decrease in yearly average precipitation during the studied period has not only caused overuse of groundwater as the primary water resources but also led to a significant decline in its chemical quality.

Prevalence of increased intraocular pressure in patients with Graves' ophthalmopathy and association with ophthalmic signs and symptoms in the north-west of Iran.

INTRODUCTION: Graves' ophthalmopathy (GO) is the most common extra-thyroidal manifestation of Graves' disease and is characterized by multiple ocular symptoms such as eyelid retraction, lid lag, proptosis, elevated intraocular pressure (IOP) and ultimately loss of vision. We aimed to investigate the prevalence of increased IOP in Graves' patients and association with ophthalmic signs and symptoms in north-west of Iran. MATERIALS AND METHODS: This descriptive cross-sectional study recruited 93 patients with GO who were diagnosed based on clinical and laboratory examinations. A complete ocular examination and IOP measurements on forward gaze were performed using Goldman applanation tonometer. RESULTS: In this study, 93 patients with GO were evaluated from 2016 to 2017. Among these patients, 67 (72.05%) were female and 27 (27.95%) were male. The most common complaints of patients were lid retraction (62.36%), puffy eyelids (58.06%) and proptosis (46.23%), respectively. The duration of disease was 0-24 months in most patients. Most subjects were at grade 3 according to NOSPECS classification. Nine patients (9.6%) had an IOP greater than or equal to 21 mmHg. The mean IOP in subjects was 16.61±3.42 mmHg. The mean IOP in males and smokers was significantly higher than that of females and nonsmokers. The mean IOP increased significantly with a higher grade of disease, duration of disease, age and smoking. CONCLUSIONS: According to the results, females comprised the majority of the study population, while ocular complications were more prevalent among males. The highest IOP was seen in old cases of GO. The most prevalent ocular signs in patients were eyelid retraction and periorbital edema. The least prevalent sign was glaucomatous optic neuropathy. In this study, the prevalence of intra-ocular hypertension was higher than that of the general population, especially in males, old cases with a drug history of antithyroid medication and smokers.

Gibbsian Thermodynamic Study of Capillary Meniscus Depth.

In the presence of gravity or other external fields, liquid surface curvature deviates from a spherical shape and the surface configuration can be found by numerical integration of the Young-Laplace equation and the typical initial point for integration is the apex of the interface. The meniscus shape in large Bond number systems, which have the central portion of the interface flattened, cannot be determined with the apex as the initial point for integration. Here we find the depth of capillary menisci by considering an initial point for integration to be at the three-phase-contact-line (TPCL) and evaluate the curvature at the TPCL by free energy analysis and inspect the effect of different parameters on the interface shape. A new parameter-which is the deviation of equilibrium curvature at the TPCL from the spherical shape (SR)-is introduced and inspected and it was found that at a Bond number of 13 the maximum deviation, approximately 0.8 of spherical curvature, takes place while for large enough Bond numbers the curvature at the three-phase contact line is near the spherical shape (0.95 < SR < 1). A potential application of this approach is to measure the capillary rise at the TPCL to find the surface tension in high Bond number systems such as those with low surface/interfacial tensions.

Organic contaminants removal from industrial wastewater by CTAB treated synthetic zeolite Y.

Due to environmental issues, wastewater treatment is a main concern for most industries and providing access to clean and affordable water is one of the big challenges. Besides, industrial wastewater contains many pollutants, one of the most toxic contaminants is organics. Currently, zeolites are widely used as an adsorbent to remove such pollutants. This study examines a surfactant modified zeolite Y (SMZY), as an applicable solution, to get over this problem. Here, zeolite Y, synthesized from bentonite, is used as an adsorbent basis. Then, it is characterized by XRD, FTIR, BET, SEM, and TGA. Next, it is modified by hexadecyltrimethyl ammonium bromide (CTAB) surfactant in different concentrations. These SMZYs are used to adsorb organic contaminants of an olefin plant wastewater. Based on adsorption capacity evaluated by several isotherms, such as Langmuir, Freundlich, Sips and Dubinin-Radushkevich, total organic carbon (TOC) content of wastewater reduced up to 89%. The optimum modification method and possible mechanism for obtaining this result is presented in the current research. Furthermore, to understand the nature of adsorption process, Van der Waals, hydrophobic, and electrostatic interactions are determined. The results indicate that adsorption process depends on both hydrophobic and electrostatic interactions.

Microbiological study of dacryocystitis in northwest of Iran.

BACKGROUND: The prevalence of bacterial pathogens isolated from patients with acute and chronic dacryocystitis and the pattern of antibiotic susceptibility tests are varied in each region. Moreover, the management of dacryocystitis is only based on clinical observations without microbiological evaluation. The present study aimed to identify epidemiologic and etiologic factors of dacryocystitis in our geographical area. MATERIALS AND METHODS: This cross-sectional and analytical study was carried out in the ophthalmology department of Hamadan University of Medical Sciences (northwest of Iran) during 2016-2017. Nasolacrimal duct discharges were inoculated to culture media including blood agar, eosin methylene blue, chocolate agar, and Sabouraud agar for the determination of microbial agents. Disc diffusion method with MAST antibiogram discs was used for antibiotic susceptibility tests, according to the Clinical and Laboratory Standards Institute, 2017. RESULTS: Of the total 129 patients enrolled in the study, 34.1% had acute dacryocystitis and 65.9% showed chronic type. The result of culture was positive in 75.2% of patients. Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Pseudomonas spp., and Candida albicans were the most prevalent microorganisms. The most sensitive antibiotics used against prevalent bacteria were ciprofloxacin (75.9%), ceftriaxone (73.6%), vancomycin (67.8%), and chloramphenicol (60.9%), respectively. CONCLUSION: The present study is useful for determining the appropriate antibiotic for systemic treatment of dacryocystitis in our region. Ciprofloxacin and vancomycin are the most sensitive antibiotics against the most common isolated microorganisms in both age groups (under and above 10 years) that can be used for empirical therapy of dacryocystitis in both acute and chronic type.

Role of precipitating solute curvature on microdrops and nanodrops during concentrating processes: the Nonideal Ostwald-Freundlich equation.

The microdrop concentrating process, which is one of the manipulations in the microdrop platform of microfluidic technologies, is a useful technique, especially in biological applications. This process may encounter a solute precipitation within the droplet if the solute reaches its solubility limit. In the case of very small solid precipitates, the solid particle size will affect the solubility limit, and the Ostwald-Freundlich equation (OFE) describes this dependency. Including the OFE in analysis affects the design parameters for this type of system and the system's thermodynamic stability. Here, by means of Gibbsian surface thermodynamics, we provide the thermodynamic description and stability analysis of this system considering the role of the Ostwald-Freundlich equation. Previously we have investigated the stability of the system without considering the OFE, which is equivalent to using a constant solubility limit. Herein it is shown that the OFE significantly affects the results for nanometer drop sizes and that various stability behaviors are possible.

Stability analysis of microdrops during concentrating processes.

Microdrop platforms in microfluidic technologies provide developments for the study of a variety of systems by means of micrometer sized fluids. Concentrating the solutes within an aqueous microdrop via slight dissolution of water into a surrounding organic phase is a process which has important applications in biological systems. In our previous work we described the thermodynamic equilibrium of this concentrating process for two types of solutes, those with limited and unlimited solubility, and investigated the role of temperature, the amount of organic phase, and the initial concentration of the solutes. It was found that, during the concentration process which is accompanied by microdrop shrinkage, for specific initial conditions the system may encounter more than one equilibrium state. In this work, by means of free energy analysis based on Gibbsian surface thermodynamics, we investigate the stability behavior of the system to provide more detailed information so that these systems can be designed more accurately.

Design of microdrop concentrating processes.

Concentrating solutes within aqueous microdrops is one of the processes that have been investigated recently in microfluidic systems. In order to design the process of concentrating solutes within microdrops more precisely, thermodynamic investigation of the process plays an important role. By knowing the equilibrium concentration and size of the drop, the magnitude of the driving force toward equilibrium will be determined which will help researchers to design such processes more accurately. Here, we have investigated the thermodynamic equilibrium of microdrop concentrating processes involving two kinds of solutes: glycerol as a solute with no solubility limit and sodium chloride as a solute with a solubility limit. It is found that the presence of a solubility limit affects the equilibrium of the process significantly in terms of trends in equilibrium concentration and size.

Thermodynamic investigation of the barrier for heterogeneous nucleation on a fluid surface in comparison with a rigid surface.

When a vapor phase is in contact with a solid or nonvolatile fluid, under conditions where the vapor is thermodynamically metastable to condensation, a droplet may nucleate from the vapor either homogenously within the vapor phase, or heterogeneously at the solid or fluid substrate interface. The case where the droplet is thermodynamically favored to nucleate heterogeneously is the subject of this article. The heterogeneous nucleation of a sessile drop on a soft surface has been studied many times experimentally and theoretically. It has been observed experimentally that heterogeneous nucleation happens faster on a soft surface in comparison with a rigid surface. Here we use Gibbsian surface thermodynamics to provide a physical understanding for this observation. Due to the difficulties of considering soft-elastic surfaces, we demonstrate that by considering only the fluidity of a surface (i.e., by considering a fluid surface as an infinitely soft material and comparing a fluid surface with a rigid surface), thermodynamics will predict that heterogeneous nucleation is easier on soft surfaces compared with rigid surfaces. We first investigate the effect of contact angle on the barrier for heterogeneous nucleation on rigid substrates at constant vapor phase pressure. Then we find a lower energy barrier for heterogeneous nucleation at a fluid surface in comparison with heterogeneous nucleation at a rigid surface which explains the faster nucleation on soft surfaces compared with rigid surfaces. Finally we inspect the role of each contribution to the energy barrier.

Aspheric profile versus wavefront-guided ablation photorefractive keratectomy for the correction of myopia using the Allegretto Eye Q.

PURPOSE: To compare the results of photorefractive keratectomy (PRK) with Q-factor customized aspheric ablation and wavefront-guided customized ablation for correction of myopia compound with astigmatism. METHODS: Fifty-six patients were enrolled in this prospective controlled study. In each patient, one eye was randomly assigned for treatment with the Q-factor customized PRK (custom-Q study group) and the other eye treated with wavefront-guided customized PRK. Preoperative and 3-month postoperative manifest refraction, contrast sensitivity, visual acuity, aberrometry, and asphericity of the cornea were compared between the two groups. All eyes were treated with the Wavelight Eye-Q 400 Hz excimer laser in a single refractive surgery center by a single surgeon. RESULTS: Uncorrected visual acuity (UCVA) improved to 20/20 or more and 20/25 or more in 34 eyes (60.7%) and 56 eyes (100%), respectively, in the wavefront-guided ablation group and in 36 eyes (64.2%) and 54 eyes (96.4%) in the custom-Q ablation group. All eyes had UCVA of 20/40 or better. A total of 54 eyes (96.4%) in the wavefront-guided ablation group and 56 (100%) in the custom-Q ablation group had spherical equivalent (SE) within -/+0.5 D. One eye in each group (2%) lost >or=2 lines of best-corrected visual acuity (BCVA). High order root mean square (RMS) in the wavefront-guided group was 0.3630-/+0.13 mum preoperatively and 0.427-/+0.17 at 3 months (p=0.2). In the custom-Q ablation group it was 0.329-/+0.092 preoperatively and 0.4730-/+0.181 at 3 months after PRK (p=0.08). CONCLUSIONS: Regarding safety and refractive efficacy, custom-Q ablation profiles were clinically equivalent to wavefront-guided profiles in corrections of myopia up to -6.00 D and astigmatism up to 2.50 D.