Cotton Gauze Research Articles

Impregnated layer combustion synthesis of co doped ZnO green nanopigments: Using nature-based cellulosic templates

In this research, nanostructured green pigments of ZnO and Co (CoxZn1-xO) were synthesized using impregnated layer combustion synthesis under microwave radiation. Taguchi design of experiments was employed to systematically investigate the influence of variables including the type of fuel, cobalt percentage, fuel to oxidizer ratio and type of template (impregnated active layer) to minimize the average crystallite size of particles. Three different types of fuels such as xylitol, mannitol and sorbitol as well as three templates containing filter paper, cotton and sterile gauze were used for the first time for synthesizing CoxZn1-xO nanopigments. The optimum sample with the average crystallite size of 35 nm was synthesized in specific conditions including mannitol as a fuel, filter paper as a template, cobalt percentage of 7%, fuel to oxidizer ratio of 1.3× stoichiometry. XRD analysis demonstrated that whole samples have followed ZnO pattern representative pure phases in the final structure and well-doped Co2+. FESEM images revealed the homogeneity of the nanoparticles, with average particle size of 90 nm. As a result of colorimetric studies on the optimum sample a broad reflectance band nearby 520 nm demonstrates green region with L* = 58.19, a* = −13.65, C* = 14.35 and h° = 162.07. Results showed that the pigment calcination influences the reflectance intensity effectively (∼40%). Co percentage and template type are the most important factors affecting the final green product colorimetric properties.

Novel 3D porous aerogels engineered at nano scale from cellulose nano fibers and curcumin: An effective treatment for chronic wounds

Traditional cotton gauze derived from cellulose has many limitations in the processes of wound healing. To overcome these hassles, we used cellulose nanofibers (CNF) incorporated with curcumin for the fabrication of wound healing 3D porous aerogel. Cellulose nanofibers synthesized from plant waste are promising sustainable nanomaterials due to their biocompatibility and biodegradability. Ionic cross linking with sodium alginate was performed to maintain the mechanical strength. SEM results revealed highly porous architecture that effectively promoted wound healing, as a result of macro- and micro-porous architecture and curcumin. In-vitro drug release studies showed a slow and steady release pattern. The 3D porous nano bio aerogel with curcumin significantly promoted the migration of fibroblast cells and had excellent antimicrobial activity against pathogenic microorganisms. In-vivo studies showed angiogenesis without rejection or inflammation of the scaffold. From the observations, we can conclude that this novel 3D porous aerogel can be used to treat chronic wounds.

Effects of Natural Brown Cotton Bleached Gauze on Wound Healing.

Natural brown cotton has favorable antibacterial and antioxidant properties. In this study, we explored the effect of gauze made from natural brown cotton after scouring and bleaching on wound healing in rats. In this work, a control experiment was adopted. The control group used absorbent cotton gauze, and the experimental group utilized natural brown cotton bleached gauze. The materials were applied to rat models to explore the effects of the two dressings on wound healing. By analyzing the wound healing state of rats, calculating the healing rate, and combining the pathological HE staining, Masson staining, and CD31 immunohistochemical staining, the results showed that both gauzes have positive effects on the wound healing of the rats. Moreover, compared with the control group, the wound healing rate of rats in the experimental group increased by 14.81%, the number of inflammatory cells decreased by 12.93%, the number of new blood vessels increased by 6.88%, the growth rate of the granulation tissue area was 10.76%, the step-up rate of the area occupied by collagen was 33.71%, and the increase rate of optical density value was 10.00%. This study found that natural brown cotton bleached gauze has a better effect on wound healing than ordinary absorbent cotton gauze, and can be used as medical dressings.

Cotton fiber-anchored binary PANI and LDH composite for removal of ketoprofen in environmental water samples

The efficient removal of ketoprofen, a non-steroidal anti-inflammatory drug, has attracted more and more attention. In this study, cotton fiber-anchored binary PANI and LDH composite (CF@PANI@LDH) was developed by in-situ growth of Ni/Al layered double hydroxide plates onto polyaniline-wrapped cotton gauze that effectively made full use of the synergistic effect of the two components, and used to remove ketoprofen from aqueous media by adsorption with the advantage of being directly taken out from solution. Various adsorption capacity influence factors, e.g., concentration, pH value, adsorption time and background ions, were studied systematically. In addition, the adsorption mechanism was explored by Fourier transform infrared spectroscopy, there existed ion exchange, hydrogen bonding and π-π interactions between the absorbent and ketoprofen. Besides, the adsorption kinetics and isotherms were supported by the pseudo-second-order model and Freundlich isotherm model, respectively. Furthermore, after 6 regeneration cycles, the fabricated CF@PANI@LDH composite still remained high adsorption capacity. More importantly, the ketoprofen removal efficiency reached higher than 82% in real environmental water samples with 0.5 g L-1 adsorbent. All the experimental data suggest that the fabricated CF@PANI@LDH composite exhibits high potential application value for the removal of ketoprofen in environmental water samples.

A novel approach to combat the spread of coronavirus and other respiratory infections with the aid of a smart sanitizing respirator

A novel approach to combat the spread of coronavirus and other respiratory infections with the aid of a smart sanitizing respirator

Antimicrobial cotton gauzes modified with poly(acrylic acid-co-maltodextrin) hydrogel using chitosan as crosslinker.

Cotton gauzes were grafted with a hydrogel of maltodextrin (MD) and poly(acrylic acid) (PAAc) using N-maleyl chitosan as crosslinker to obtain materials with antimicrobial properties. Reaction parameters including monomer, crosslinker, and initiator concentrations were studied. The modification with the copolymer poly(acrylic acid)-co-maltodextrin (PAAc-co-MD) was corroborated by Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). The grafted gauzes (gauze-g-(PAAc-co-MD)) were able to load vancomycin and inhibit the growth of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria. In addition, the incorporation of chitosan as crosslinker showed a synergistic effect against these bacteria. The prepared gauze-g-(PAAc-co-MD) materials could be used in the biomedical area particularly as antimicrobial wound dressings.

Efficient, biosafe and tissue adhesive hemostatic cotton gauze with controlled balance of hydrophilicity and hydrophobicity

Cotton gauze is a widely used topical hemostatic material for bleeding control, but its high blood absorption capacity tends to cause extra blood loss. Therefore, development of rapid hemostatic cotton gauze with less blood loss is of great significance. Here, we develop an efficient hemostatic cotton gauze whose surface is slightly modified with a catechol compound which features a flexible long hydrophobic alkyl chain terminated with a catechol group. Its hemostatic performance in animal injuries is superior to standard cotton gauze and Combat GauzeTM. Its biosafety is similar to cotton gauze and rebleeding hardly occurs when the gauze is removed. Here, we show its hemostatic capability is attributable to the rapid formation of big and thick primary erythrocyte clots, due to its effective controlling of blood movement through blocking effect from tissue adhesion by catechol, blood wicking in cotton, and the hydrophobic effect from long alkyl chains.

Chitosan and polyhexamethylene guanidine dual-functionalized cotton gauze as a versatile bandage for the management of chronic wounds

Development of versatile medical dressing with good immediate and long-lasting antibacterial, hygroscopic and moisturizing abilities is of great significance for management of chronic wounds. Cotton gauze (CG) can protect wounds and promote scabbing, but can cause wound dehydration and loss of biologically active substances, thereby greatly delays wound healing. Herein, a bi-functional CG dressing (CPCG) was developed by chemically grafting polyhexamethylene guanidine (PHMG) and physically adsorbing chitosan (CS) onto the CG surface. Due to the powerful microbicidal activity of PHMG, CPCG exhibited excellent immediate and long-lasting antibacterial activity against gram-positive and gram-negative bacteria. Moreover, the abundant hydroxyl and amino groups in CS endowed CPCG with good biocompatibility, moisture absorption, moisturizing and cell scratch healing performances. Importantly, CPCG can be easily fabricated into a bandage to conveniently manage infected full-skin wounds. Together, this study suggests that CPCG is a versatile wound dressing, having enormous application potential for management chronic wounds.

Nanocomposite cotton gauze cloth with in situ generated silver, copper and their binary metal nanoparticles by bioreduction method

In the present work, the authors prepared nanocomposite cotton gauze cloth (NCGC) by in situ generating the nanoparticles of silver (ANPs) and copper (CuNPs) and their binary metallic nanoparticles (BMNPs) using aqueous extraction of Azadirachta indica leaves as a reducing agent. The NCGCs had roughly spherical AgNPs, CuNPs and BMNPs in the size range of 50–120 nm. The corresponding mean size of the spherical AgNPs, CuNPs and BMNPs was 94, 89 and 87 nm respectively. The participation of the hydroxyl and amino groups of the leaf extract in the generation of the metal nanoparticles in the NCGCs was established by studying the chemical interactions. All the NCGC specimens exhibited significant antibacterial activity. However, the NCGCs with BMNPs had higher antibacterial efficiency when compared to those with homo metal nanoparticles. Hence, the NCGC with generated BMNPs can be effectively used as antibacterial wound dressing material.

Microencapsulated sodium fusidate to impart antibacterial properties into cotton dressings for traumatic wounds.

This research aimed to investigate the use of microencapsulated sodium fusidate to impart antibacterial properties into conventional cotton gauze used to treat traumatic wounds. The microcapsules were prepared with sodium fusidate dissolved in ethanol as the active substance (core) and calcium alginate as the wall material (shell) using an electrospraying method. The microcapsules were then loaded into a 1% solution of chitosan, and conventional sterile cotton gauze fabric was impregnated in this suspension and dried at room temperature. The microcapsules obtained were examined with Fourier transform infrared spectroscopy to confirm the constituents, and by scanning electron microscopy to examine the size and distribution of the microcapsules. The results showed that microcapsules with sodium fusidate as the core material were produced in a size range of 50-200µm. The antibacterial properties of these gauze samples were tested for resistance to both Gram-positive and Gram-negative bacteria. The samples showed antibacterial properties against Gram-positive bacteria (Staphylococcus aureus) only, with an average inhibition zone of 31.67±2.89mm in diameter. The antibacterial effect of the treated gauze samples was tested after washing to investigate the strength of the binding agent, to find out whether the samples maintained antibacterial properties after two hand-rubbed washes. Its absorption capacity, rate of absorbency and air permeability values were 555±4.51%, 1.25±0.04 seconds and 408±2.65cm3/cm2/seconds, respectively. The research findings have established the possibility of imparting antibacterial properties into sterile cotton gauze using microencapsulation of sodium fusidate.

Characterization of Macrophage and Cytokine Interactions with Biomaterials Used in Negative-Pressure Wound Therapy.

Macrophages are innate immune cells that help wounds heal. Here, we study the potential immunomodulatory effects of negative-pressure wound therapy (NPWT) materials on the macrophage inflammatory response. We compared the effects of two materials, Granufoam™ (GF) and Veraflo Cleanse™ (VC), on macrophage function in vitro. We find that both materials cause reduced expression of inflammatory genes, such as TNF and IL1B, in human macrophages stimulated with bacterial lipopolysaccharide (LPS) and interferon-gamma (IFNγ). Relative to adherent glass control surfaces, VC discourages macrophage adhesion and spreading, and may potentially sequester LPS/IFNγ and cytokines that the cells produce. GF, on the other hand, was less suppressive of inflammation, supported macrophage adhesion and spreading better than VC, and sequestered lesser quantities of LPS/IFNγ in comparison to VC. The control dressing material cotton gauze (CT) was also immunosuppressive, capable of TNF-α retention and LPS/IFNγ sequestration. Our findings suggest that NPWT material interactions with cells, as well as soluble factors including cytokines and LPS, can modulate the immune response, independent of vacuum application. We have also established methodological strategies for studying NPWT materials and reveal the potential utility of cell-based in vitro studies for elucidating biological effects of NPWT materials.

Effects of solvents on electrospun fibers and the biological application of different hydrophilic electrospun mats

It is reported that low volatile solvent could slow down the rate of solvent volatilization during the electrospinning process and hydrophobic biomaterials were easily to form branching fiber, which would be used as a potential biomaterial as wound dressing because of its bacterial barrier property. In this work, silver ion (Ag+) was used as the anti-bacterial components to explore the effect of N, N-dimethylformamide (DMF) as a fiber differentiation inducer on hydrophilic materials-Polyvinyl alcohol (PVA), Polyvinylpyrrolidone (PVP) and Eudragit L-100 during the electrospinning. The results of scanning electron microscopy (SEM) and X-ray diffraction (XRD) confirmed that DMF could reduce the diameter of electrospun fibers and increased crystallinity of the electrospun fibers. The results of water absorption test, X-ray photoelectron spectroscopy (XPS) and in vitro antibacterial activity showed that comparing with cotton non-woven fabric, gauze and cotton, the fiber with strong water absorption could load more silver ions and had stronger inhibitory properties against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). CCK-8 assay showed that the cytotoxicity of DMF induced hydrophilic material electrospun fibers and their silver loaded electrospun fibers were all above 90%, which suggested that the fibers could be developed for clinical application. This work could provide an opportunity for improving the properties of electrospun fibers which have potential to be applied as wound dressings.

Eco-Friendly Superhydrophobic Composites with Thermostability, UV Resistance, and Coating Transparency.

Despite the market demand for biofiber assemblies endowed with superhydrophobicity being huge, the current approaches to their production are complicated, time-consuming, and even pose a serious threat to the environment. Here, we report a simple surface treatment strategy to prepare environmentally friendly superhydrophobic biofiber composites. The obtained samples have certain UV resistance properties, which are mainly determined by the titanium dioxide (TiO2) dosage. Additionally, the sample has excellent thermal stability, and the contact angle is maintained at 153.26° after heat treatment at 140 °C for 1 h. Quite encouragingly, thermal annealing of samples can transform translucent coatings into transparent structures and increase the tensile strength. The results also showed that this strategy could be integrated into the mass production process of other biofiber components as coating, such as coated paper, pulp boards, cotton gauzes, tissues, and so forth. Due to the facile preparation and environment-friendliness, this sustainable paper-based product can be used in diversified applications: packaging and storage of liquid food, protection of ancient books, UV- and rain-proof materials, and teaching demonstrations relevant to bionics, among others.

Forensic examination of textile fibres using Raman imaging and multivariate analysis

Vibrational spectroscopic techniques have shown to be highly suitable for the identification and comparison of textile fibres and clothing fabrics. On the other hand, new chemical imaging modes based on these spectroscopic techniques are becoming useful in multiple fields. This is particularly important to, for instance, chemically visualize and screen different samples including forensic evidence (crime scene investigation), chemical and food products (quality control), biological tissues and living beings (medical imaging), among others. This study explores the forensic examination and selective chemical visualization of textile fibres and clothing fabrics using Raman imaging. Four experiments were performed, which were focused on the screening of (i) white different materials made of 100 % cotton (gauze, cotton wool, t-shirt, and swab), (ii) polyester and cotton fabrics evidence of the same colour, (iii) five different coloured cotton fabrics, and (iv) textile fibres of different materials (acrylic, cotton, nylon, polyester, and silk). Several methods of multivariate chemometric analysis including principal component analysis (PCA), multivariate analysis of variance (MANOVA), and multivariate curve resolution (MCR) were applied to enhance the limited visual comparison of the spectra accomplished with the unaided eye. The results evidenced the suitability of Raman imaging to statistically discriminate textile fibres and fabrics due to the chemical composition of both the clothing material and the dyestuff.

Erythritol air polishing in the surgical treatment of peri-implantitis: A randomized controlled trial.

ObjectivesTo compare erythritol air polishing with implant surface cleansing using saline during the surgical treatment of peri‐implantitis.Material and MethodsDuring a resective surgical intervention, implant surfaces were randomly treated with either air polishing (test group n = 26 patients/53 implants) or saline‐soaked cotton gauzes (control group n = 31 patients/ 40 implants). Primary outcome was change in mean bleeding on probing (BoP) from baseline to 12 months follow‐up. Secondary outcomes were changes in mean suppuration on probing (SoP), plaque score (Plq), probing pocket depth (PPD), marginal bone loss (MBL), periodontal full‐mouth scores (PFMS), and levels of 8 classical periodontal pathogens. Clinical and radiographical parameters were analyzed using multilevel regression analyses. Microbiological outcomes were analyzed using the Mann–Whitney U test.ResultsNo differences between the test and control group were found for BoP over 12 months of follow‐up, nor for the secondary parameters Plq, PPD, and MBL. Between both groups, a significant difference was found for the levels of SoP (p = 0.035). No significant effect on microbiological levels was found. A total number of 6 implants were lost in the test group and 10 in the control group. At 1‐year follow‐up, a successful treatment outcome (PPD<5 mm, max 1 out of 6 sites BoP, no suppuration and no progressive bone loss >0.5 mm) was achieved for a total of 18 implants (19.2%).ConclusionsErythritol air polishing as implant surface cleansing method was not more effective than saline during resective surgical treatment of peri‐implantitis in terms of clinical, radiographical, and microbiological parameters. Both therapies resulted in low treatment success.Trial registry: https://www.trialregister.nl/ Identifier: NL8621.

Development of a refined ex vivo model of peritoneal adhesion formation, and a role for connexin 43 in their development.

Despite many advances across the surgical sciences, post-surgical peritoneal adhesions still pose a considerable risk in modern-day procedures and are highly undesirable. We have developed a novel mouse peritoneal strip ex vivo adhesion model which may serve to bridge the gap between single cell culture systems and in vivo animal drug testing for the assessment of potential anti-adhesion agents, and study of causality of the process. We investigated the optimal conditions for adhesion formation with mouse peritoneal tissue strips by modifying an existing ex vivo rat model of peritoneal adhesions. We assessed the impact of the following conditions on the formation of adhesions: contact pressure, abrasions, and the presence of clotted blood. Macroscopic adhesions were detected in all mouse peritoneal strips exposed to specific conditions, namely abrasions and clotted blood, where peritoneal surfaces were kept in contact with pressure using cotton gauze in a tissue cassette. Adhesions were confirmed microscopically. Interestingly, connexin 43, a gap junction protein, was found to be upregulated at sites of adhesions. Key features of this model were the use of padding the abraded tissue with gauze and the use of a standardised volume of clotted blood. Using this model, peritoneal strips cultured with clotted blood between abraded surfaces were found to reproducibly develop adhesion bands at 72h. Our goal is to develop a model that can be used in genetically modified mice in order to dissect out the role of particular genes in adhesion formation and to test drugs to prevent adhesion formation.

RESULTS OF THE STUDY OF THE POULTRY MANURE MICROFLORA

The microbiological composition of chicken manure has a significant impact on its further destruction. For the disposal of chicken manure by biological methods it is important to have in the manure nutrients, growth inhibitors (residues of antibiotics or disinfectants), the ratio of spore-forming and non-spore-forming microflora, as well as the presence of beneficial microflora. The aim of the work was to study the microbiological composition of chicken manure in poultry farms of Ukraine.&#x0D; Chicken manure from poultry farms of different scale and method of keeping poultry on the territory of Ukraine was studied. Selected samples were transported in a thermal container and examined microbiologically by inoculation on commonly used and selective media. To determine the amount of spore-forming microflora, a slurry suspension was prepared, sown in a mattress with a dense nutrient medium and turpentine was introduced into a cotton gauze plug. The morphology of the isolated microorganisms, acid-forming properties, catalase activity and enzymatic properties were studied according to generally accepted methods.&#x0D; It was found that in the manure of chickens, which were kept indoors, the percentage of spore-forming microorganisms ranged from 14.74 to 21.24 %, and not spore-forming – 78.76-85.26 %. In the manure of chickens that had grazed, the percentage of spore-forming microorganisms ranged from 48.93 to 78.81 %, and not spore-forming – 21.19-51.07 %. The average amount of spore-forming microflora under both conditions was 40.86 %, and not spore-forming – 59.14 %. According to the results of the work, 20 isolates were isolated, of which 15% of isolates had pronounced acid-forming properties. On MRS agar, the isolates had the appearance of small, smooth white-gray S-shaped colonies, in Gram-stained smears, small gram-positive rods were observed, arranged singly, in pairs, and in short chains. Isolates 1, 2 and 3 had a negative reaction to catalase.&#x0D; According to the results of the studies, isolate 1 was identified as Lactobacillus salivarius subsp. salivarius, isolate 2 – Lactobacillus reuteri, and isolate 3 – Lactobacillus delbrueckii.

Gallocatechin‑silver nanoparticle impregnated cotton gauze patches enhance wound healing in diabetic rats by suppressing oxidative stress and inflammation via modulating the Nrf2/HO-1 and TLR4/NF-κB pathways

This study is designed to investigate the combination of gallocatechin (GC) and silver nanoparticles (AgNPs) for its wound healing ability in diabetic rats. Thirty male Sprague Dawley rats were randomly divided into 5 groups: 1. Normal control rats dressed with blank CGP1; 2. Diabetic rats dressed with blank CGP1; 3. Diabetic rats dressed with 13.06μM of GC; 4. Diabetic rats dressed with 26.12 μM of GC; 5. Diabetic rats dressed with 0.1% silver sulfadiazine patches. GC-AgNPs-CGP dressed diabetic rats showed significant FBG reduction, prevented the body weight losses and reduced the oxidative stress by lowering MDA content and elevated antioxidant enzymes such as SOD, CAT and GPx in wound healing skin of diabetic rats when compared to normal CGP. Besides, mRNA expression of Nrf2, Nqo-1, and Ho-1 was upregulated with downregulated expression of Keap-1 mRNA, which is supported by immunohistochemistry. Furthermore, GC-AgNPs-CGP dressing increased growth factors such as VEGF, EGF, TGF-β, and FGF-2 while decreasing MMP-2 in the skin of diabetic wound rats. In vitro permeation study demonstrated rapid GC release and permeation with a flux of 0.061 and 0.143 mg/sq.cm/h. In conclusion, the results indicated that GC-AgNPs-CGP dressing on diabetic wound rats modulated oxidative stress and inflammation with elevated growth factors; increased collagen synthesis thereby significantly improved the wound healing and could be beneficial for the management of diabetic wounds.

Greener therapeutic pH-sensing wound dressing based on Curcuma Longa and cellulose hydrogel

• pH-sensing wound dressing was developed to indicate the wound healing status. • Curcuma Longa extract was used as easy and cost-effective pH monitoring detector. • Transparent, soft and neutral hydrogels were prepared based on green monomer. • Hydrogel matrix loaded on cotton gauze showed explicit color changes as pH changes. The moist dressing has been taken as an approach to maintain a wet environment for the wound and accelerate its healing process. Recently, more functionality has been imparted to wound dressings to monitor changes in skin pH and visually indicate the wound healing status. However, providing a biocompatible pH-sensing hydrogel made of green components, at a neutral medium, is yet to investigate. In this work, pH-sensitive natural dye, Curcuma Longa extract (CLE), was utilized as an easy and cost-effective pH-sensitive indicator. CLE was loaded in hydrogel made of hydroxyethyl cellulose grafted with green monomer, itaconic acid (IA), to prepare transparent, soft, and neutral pH-sensitive wound dressing. IA concentrations tuned gel porous structure (370–100 µm), mechanical (686–1186 N, load at break), swelling (up to1839% at neutral medium), and release properties. Hydrogel showed higher release percentages at pH (7.4), and longer release profiles at pH (8 ± 0.2) which suits wound healing applications. The coloristic properties of the CLE as a function of pH were confirmed by UV–Vis spectroscopy. Hydrogel matrices, loaded on cotton gauze and submerged in different pH buffer solutions, showed explicit color changes from visibly yellow for pH ≤ 7 and dark red for pH > 7.

Paraffin-Coated Hydrophobic Hemostatic Zeolite Gauze for Rapid Coagulation with Minimal Adhesion.

To solve the problem of strong adhesion and excessive blood loss caused by the use of hydrophilic zeolite gauze (Z-Gauze) in uncontrollable bleeding, we have modified the surface of commercial Z-Gauze with a paraffin coating and prepared a hydrophobic dressing PZ-Gauze. After paraffin coating, the adhesion of Z-Gauze was reduced without an obvious decrease in coagulation activity. The clotting time of the hydrophobic PZ-Gauze was reduced from 378.3 to 154.6 s compared with that of cotton gauze, and the peeling force was decreased from 348.8 to 84.7 mN compared with that of Z-Gauze. Besides, PZ-Gauze can efficiently cut down the blood loss during treatment. On the basis of in vitro and in vivo experiments, it is confirmed that surface hydrophobic modification does not change the procoagulant performance because of the maintained cation exchange capacity of zeolites, and the reduced blood loss as well as enhanced difficulty for fibrin adhesion is attributed to its hydrophobicity. This is different from the traditional gauze procoagulant theories, where gauze hydrophilicity and procoagulant performance are always positively correlated.