Optimizing ReBreed21 II: Fertility and reproductive efficiency in different parities during a shortened breeding season in beef cattle.

This study evaluated the efficiency of a rapid reinsemination program allowing timed AI (TAI) every 21d (ReBreed21) in a commercial beef cow-calf operation. Nelore females from different parities (n = 2085) were synchronized for first TAI (D0 = TAI) using an estradiol/progesterone (E2/P4) protocol and assigned to one of three reinsemination programs: Resynch33 (n = 753), traditional resynch program with second TAI at D42 after first TAI; ReBreed21 (n = 687); or ReBreed21+EC (n = 670). The ReBreed females (n = 1357) received intravaginal P4 insert on D12, on D19 P4 was removed, and a dose of equine chorionic gonadotropin (eCG) was administered, then, ReBreed21 females received 0.6 mg of EC (ReBreed21+EC) or nothing (ReBreed21) and on D21, nonpregnancy (NP) was determined using Doppler ultrasound to detect corpus luteum (CL) blood flow (BF) (NP: <25 % BF pixels of total CL area) and NP cows received immediate TAI and GnRH to induce ovulation. Pregnancy diagnosis was performed at D33 after TAI following all TAIs. Cows considered pregnant at D21, based on CL BF, but NP on D33 were designated False-Positives (FP) and false negatives (FN) were number of nonpregnant cows/heifers on d21 based on the CL BF found to subsequently be pregnant on D33 divided by the total number pregnant. Pregnancy/AI (P/AI) did not differ for the first TAI (55.1 %) among the treatments. Heifers had similar P/AI at the second AI in all groups and similar to the first AI. Primiparous had greater P/AI in ReBreed21+EC and Resynch33 at s TAI compared to ReBreed21, 51.7 %, 55.8 %, 34.2 %, respectively. Multiparous had greater P/AI at second TAI in Resynch33 (60.9 %) than ReBreed21 programs (34.7 %). The percentage FP and FN among ReBreed21 programs did not differ, 13.8 and 0.2 %, respectively. Overall accumulative pregnancies on D21 of the breeding season were greater for ReBreed21 and ReBreed21+EC than Resynch33 (69.7 %, 71.6 %, and 55.5 %, respectively). However, on D42 of the breeding season, only heifers had greater pregnancies in ReBreed21 programs than Resynch33 (73.3 %, 74.3.6 %, and 63.2 %, respectively). Average days to pregnancy were less (P = 0.01) for ReBreed21 and ReBreed21+EC than Resynch33. Thus, the ReBreed21 strategy can improve the efficiency of TAI programs in beef cattle. Of interest, ReBreed21 was particularly effective in nulliparous, somewhat effective in primiparous when EC was added to the program, but relatively ineffective in multiparous beef cattle.

Early induction of luteolysis in a timed AI protocol increases reproductive performance in beef cows.

The aim of this study was to produce a longer proestrus by early administration of prostaglandin F2α (PGF) in a timed artificial insemination (TAI) protocol in non-suckling Bos taurus (Angus crossbreed) beef cows. On day 0, cows (n = 489) were treated with an intravaginal 1 g progesterone (P4) device and 2 mg of estradiol benzoate. On day 7, cows were randomized into two groups: PGF7(n = 244; 500 µg of sodium cloprostenol 24 h before P4 device removal) or PFG8 (n = 245; 500 µg of sodium cloprostenol at P4 device removal). On day 8, P4 device was removed and cows received 0.5 mg of estradiol cypionate. All cows were submitted to TAI on day 10 (48-50 hours after P4 device removal). Cows treated with PGF on day 7 had greater expression of estrus (91.3 vs 79.1 %; P = 0.0011), regardless of CL presence at beginning of the protocol. Cows from PGF7 group had lower circulating P4 concentrations on day 8 in comparison with PGF8 treated cows (1.86 vs 2.99 ng/mL; P < 0.001). However, preovulatory follicle diameter did not differ among treatments at TAI (11.9 vs 11.8 mm; P = 0.7881). Pregnancy per TAI (P/TAI) was greater for PGF7 (63.9 vs 50.6 %; P = 0.0114) than PGF8 treated cows. In cows with follicles <8.5 mm at TAI, expression of estrus (33.3 vs 26.6 %; P = 0.6427) and P/TAI (40 vs 26.6 %; P = 0.3657) were low in both PGF7 and PGF8 treated cows, respectively. In cows with medium follicle size (8.5 to 11.9 mm) PGF7 treated cows had greater expression of estrus (90.5 vs 80 %; P = 0.033) and P/TAI (62.2 vs 49 %; P = 0.053). In cows with follicles >12 mm, expression of estrus was greater for PGF7 than PGF8 treated cows (99.1 vs 93.3 %; P = 0.045), however P/TAI did not differ (68.2 vs 59 %; P = 0.149). In cows with P4 < 1.99 ng/mL on day 8, expression of estrus was similar between PGF7 and PGF8 treated cows (92.6 vs 90.4 %; P = 0.53), and P/TAI tended to be greater for PGF7 than PGF8 treated cows (63 vs 52.1 % P = 0.076). However, in cows with P4 > 2 ng/mL PGF7 cows had higher expression of estrus (89 vs 67.5 %; P = 0.0005) and P/TAI (64.8 vs 48.7 %; P = 0.021) than PGF8. Thus, increasing the proestrous period by inducing luteolysis 24 hours earlier than removing the P4 intravaginal device enhanced fertility in non-suckling cyclic beef cows by increasing expression of estrus and P/TAI.

Long-term effectiveness and safety of edoxaban in patients with atrial fibrillation: 4-year data from the ETNA-AF-Europe study.

BACKGROUND: To assess long-term effectiveness and safety of edoxaban in Europe. METHODS AND RESULTS: ETNA-AF-Europe, a prospective, multinational, multi-centre, post-authorisation, observational study was conducted in agreement with the European Medicines Agency. The primary and secondary objectives assessed real-world safety (including bleeding and deaths) and effectiveness (including stroke, systemic embolic events and clinical edoxaban use), respectively. Median (interquartile range) age of the 13,164 patients was 75.0 (68.0-80.0) years; CHA2DS2-VASc and HAS-BLED scores were 3.0 (2.0-4.0) and 2.0 (1.0-2.0), respectively. Follow-up duration was 3.98 (3.21-4.05) years. Patients on edoxaban 30 mg (n = 3042) at baseline were older (80.0 vs 73.0 years), more likely assessed as frail by investigators (27.0% vs 6.6%) and had more comorbidities than those on edoxaban 60 mg (n = 9617; missing dosing information for n = 505). Annualised event rates of all-cause and cardiovascular death in the overall population, edoxaban 60 mg and edoxaban 30 mg groups were 4.1%, 2.8% and 8.4%, and 1.0%, 0.7% and 2.0%, respectively. Annualised rates of stroke were relatively constant throughout the follow-up, transient ischaemic attack and systemic embolism were < 1% in the overall population. Rates of any major and major gastrointestinal bleeding were low, with slightly higher rates for edoxaban 30 vs 60 mg group. Intracranial haemorrhage was uncommon (0.2%). CONCLUSIONS: In European patients with AF, long-term therapy with edoxaban is associated with low and relatively constant annualised rates of stroke and major bleeding. Differences in outcomes between the two approved doses are attributable to differences in clinical characteristics.

Validation of the Equidyn protocol for evaluation of dynamic balance in older adults through a smartphone application.

BACKGROUND: Different tasks and proxy measurements have been employed to evaluate dynamic balance in older individuals. However, due to inherent limitations, results from most evaluations could hardly be taken as valid measurements of dynamic balance. RESEARCH QUESTION: Is the Equidyn smartphone application-based protocol valid and sensitive for assessment of dynamic balance in older adults? METHODS: Dynamic balance was evaluated in 52 physically active individuals, age range 60-80 years (M = 69.36). The dynamic tasks were one-leg sway either in the mediolateral (ML) or anteroposterior (AP) direction while supported on the contralateral leg, and cyclic sit-to-stand with a narrow support base. These tasks were performed under standardized movement amplitude and rhythm. Outcomes were correlated with unipedal quiet standing. A smartphone was attached to the trunk backside, and a custom-made application (Equidyn) was employed to provide guidance throughout evaluation, timed beeps to pace the movements, and three-dimensional trunk acceleration measurement for balance evaluation. RESULTS: Our data showed (a) that both ML and AP leg sway tasks were sensitive to aging and to direction of leg sway movements; (b) referenced to quiet unipedal stance, moderate/strong correlations for the ML/AP leg sway tasks and moderate correlations for the sit-to-stand task; and (c) moderate/strong correlations between the ML and AP leg sway tasks, and moderate correlations between the sit-to-stand and the two unipedal dynamic tasks in the ML acceleration direction. SIGNIFICANCE: The current results support the conclusion that the Equidyn protocol is a sensitive and valid tool to evaluate dynamic balance in healthy older individuals. The protocol tasks standardized in amplitude and rhythm favor their reproducibility and trunk acceleration data interpretation. As the whole assessment is made through a smartphone application, this dynamic balance evaluation could be made in a low-cost simple way both in the laboratory and clinical settings.

Symmetric unipedal balance in quiet stance and dynamic tasks in older individuals.

Previous evidence of increased difference of muscular strength between the dominant and non-dominant legs in older adults suggests the possibility of dissimilar balance control between the legs (between-leg asymmetry) associated with aging. In the current investigation, we evaluated between-leg asymmetries in older adults when performing quiet and dynamic balance tasks. Fifty-two physically active and healthy older adults within the age range of 60 to 80 years were recruited. Participants performed balance tasks in unipedal stance, including quiet standing and cyclic sway (rhythmic oscillation) of the non-supporting leg in the anteroposterior or mediolateral directions, producing foot displacements with amplitudes of 20 cm paced in 1 Hz through a metronome. Body balance was evaluated through trunk accelerometry, by using the sensors embedded into a smartphone fixed at the height of the 10th-12th thoracic spines. Analysis revealed lack of significant differences in balance control between the legs either when comparing the right versus left or the preferred versus non-preferred legs, regardless of whether they were performing quiet stance or dynamic tasks. Further examination of the data showed high between-leg correlation coefficients (rs range: 0.71-0.84) across all tasks. Then, our results indicated symmetric and associated between-leg balance control in the examined older adults.

Assessing the efficacy of the 'Bicho De 7 Cabeças' B-learning school-based program in enhancing mental health literacy and reducing stigma.

The prevalence of mental disorders in adolescents has a considerable impact on daily life, restricting tasks and diminishing overall quality of life while potentially leading to stigmatization. This study aims to measure the impact of a mental health literacy intervention program, called "Bicho de 7 Cabeças" project, in b-learning format, on the increase of knowledge and the decrease of stigma in young people from Póvoa de Varzim, in Portugal. A quasi-experimental study was conducted, from November 2022 to May 2023, involving an experimental group ("Bicho de 7 Cabeças" protocol) and an active control group (informational brochures), utilizing a pre-test/post-test design. Mental Health Literacy Measure-MHLM, Mental Health Promoting Knowledge Scale-MHPK-10, Mental Illness Knowledge Schedule-MAKS, Reported and Intended Behaviour Scale-RIBS, and Community Attitudes toward People with Mental Illness-CAMI were used. A total of 504 young students from the 9th grade enroll in this study, with a mean age around 14 years old. There is a significant difference between stigma (p <.001) and knowledge (p <.001) scores at baseline and follow-up. The results of this study shows that interventions aimed at young people for the promotion of mental health literacy and stigma reduction are needed and more initiatives should be implemented in schools to address these problems.

Could driving help us to "see better"? A comparative assessment of saccadic efficiency, visual speed, and attention.

BACKGROUND: This study aimed at comparing drivers' and non-drivers' results in the Adult Developmental Eye Movement with Distractors test (ADEMd) and the Useful Field of View test (UFOV). METHODS: One hundred and twenty Spaniards (mean age 50.90 ± 17.32 years) without eye disease voluntarily participated in this cross-sectional descriptive study. Participants in a single experimental session completed a questionnaire on sociodemographic, health, eyesight, and driving information. They also performed the ADEMd and UFOV tests randomly following standardized protocols. The ADEMd is a visual-verbal test that measures saccadic efficiency and visual attention. Brown-Forsythe (B-F) tests with Games-Howell post-hoc adjustments were conducted to assess differences between groups. Groups were formed according to sex, age (young adults, adults, and older adults), and driver/non-driver for further analysis. Additionally, associations between dependent variables were assessed through Spearman's correlations. RESULTS: Drivers obtained significantly better results in the ADEMd compared with non-drivers. Non-significant differences between drivers and non-drivers were encountered in the UFOV. Additionally, significant differences were observed between sexes and age groups. It is worth highlighting that non-driver's age significantly correlated with worse ADEMd performance (rho = .637 to .716). This correlation was non-significant in drivers. Similarly, reading hours significantly correlated with better ADEMd performance in non-drivers (rho = - .291 to - .363), but not in drivers. The only significant correlations between ADEMd and UFOV tests were found in drivers (rho = .307 to .410). CONCLUSION: Considering all the discussed results, it could be hypothesized that the driving task promotes abilities, such as oculomotor and cognitive function, which are relevant for the performance in the ADEMd. However, this hypothesis is based on correlational outcomes and further studies should causally assess this possible relation.

Physiological, metabolic and hormonal responses of two Pinus spp. with contrasting susceptibility to brown-spot needle blight disease.

Needle blights are serious fungal diseases affecting European natural and planted pine forests. Brown-spot needle blight (BSNB) disease, caused by the fungus Lecanosticta acicola, causes canopy defoliation and severe productivity losses, with consequences depending on host susceptibility. To gain new insights into BSNB plant-pathogen interactions, constitutive and pathogen-induced traits were assessed in two host species with differential disease susceptibility. Six-month-old Pinus radiata D. Don (susceptible) and Pinus pinea L. (more resistant) seedlings were needle inoculated with L. acicola under controlled conditions. Eighty days after inoculation, healthy-looking needles from symptomatic plants were assessed for physiological parameters and sampled for biochemical analysis. Disease progression, plant growth, leaf gas-exchanges and biochemical parameters were complemented with hormonal and untargeted primary metabolism analysis and integrated for a holistic analysis. Constitutive differences between pine species were observed. Pinus pinea presented higher stomatal conductance and transpiration rate and higher amino and organic acids, abscisic acid as well as putrescine content than P. radiata. Symptoms from BSNB disease were observed in 54.54% of P. radiata and 45.45% of P. pinea seedlings, being more pronounced and generalized in P. radiata. For both species, plant height, sub-stomatal CO2 concentration and water-use efficiency were impacted by infection. In P. radiata, total soluble sugars, starch and total flavonoids content increased after infection. No differences in hormone content after infection were observed. However, secondary metabolism was induced in P. pinea visible through total phenolics, flavonoids and putrescine accumulation. Overall, the observed results suggest that P. pinea constitutive and induced traits may function as two layers of a defence strategy which contributed to an increased BSNB resistance in comparison with P. radiata. This is the first integrative study linking plant physiological and molecular traits in Pinus-Lecanosticta acicola pathosystem, contributing to a better understanding of the underlying resistance mechanisms to BSNB disease in pines.

Profiles of interferon-stimulated genes in multiple tissues and circulating pregnancy-associated glycoproteins and their association with pregnancy loss in dairy cows†.

Pregnancy loss (PL) in lactating dairy cows disrupts reproductive and productive efficiency. We evaluated the expression of interferon-stimulated genes (ISG) in blood leukocytes, vaginal and cervical epithelial cells, luteolysis-related genes, progesterone, and pregnancy-associated glycoprotein (PAG) profiles in lactating dairy cows (n = 86) to gain insight about PL. Expression of ISG on d17, d19, and d21 was greater in cows that maintained the pregnancy (P33) compared to nonpregnant with no PL (NP). Greater ISG differences between groups were observed in the cervix (96.7-fold) than vagina (31.0-fold), and least in blood leukocytes (5.6-fold). Based on individual profiles of ISG and PAG, PL was determined to occur either before (~13%) or after (~25%) d22. For cows with PL before d22, ISG expression was similar on d17 but by d21 was lower and OXTR was greater than P33 cows and similar to NP; timing of luteolysis was similar compared to NP cows suggesting embryonic failure to promote luteal maintenance and to attach to the endometrium (no increase in PAG). For cows with PL after d22, ISG expression was similar to P33 cows on d17, d19, and d21 and luteolysis, when it occurred, was later than NP cows; delayed increase in PAG suggested later or inadequate embryonic attachment. In conclusion, PL before d22 occurred due to embryonic demise/failure to signal for luteal maintenance, as reflected in reduced ISG expression by d21. Alternatively, embryos with PL between d22 and 33 adequately signaled for luteal maintenance (ISG) but had delayed/inadequate embryonic attachment and/or inappropriate luteolysis causing PL.

A rare case of skin metastasis from a chordoma.

Chordoma is an uncommon, indolent malignant tumor arising from notochordal remnants. The incidence of distant metastasis varies between 30 and 40% in different series. Even though local involvement of the skin by direct invasion of chordoma is common, distant skin metastasis are rare, with less than 30 cases reported in the literature. The present clinical case illustrates the slow-growing natural history of a sacral chordoma, which evolved with lung metastasis, followed three years later by skin metastasis, thus giving us the opportunity to review the diagnostic approach, as well as the clinical and histopathological characteristics of this rare tumor.

A mechanosensitive caveolae-invadosome interplay drives matrix remodelling for cancer cell invasion.

Invadosomes and caveolae are mechanosensitive structures that are implicated in metastasis. Here, we describe a unique juxtaposition of caveola clusters and matrix degradative invadosomes at contact sites between the plasma membrane of cancer cells and constricting fibrils both in 2D and 3D type I collagen matrix environments. Preferential association between caveolae and straight segments of the fibrils, and between invadosomes and bent segments of the fibrils, was observed along with matrix remodelling. Caveola recruitment precedes and is required for invadosome formation and activity. Reciprocally, invadosome disruption results in the accumulation of fibril-associated caveolae. Moreover, caveolae and the collagen receptor ß1 integrin co-localize at contact sites with the fibrils, and integrins control caveola recruitment to fibrils. In turn, caveolae mediate the clearance of ß1 integrin and collagen uptake in an invadosome-dependent and collagen-cleavage-dependent mechanism. Our data reveal a reciprocal interplay between caveolae and invadosomes that coordinates adhesion to and proteolytic remodelling of confining fibrils to support tumour cell dissemination.

Measurement of the Induced Magnetic Polarisation of Rotated-Domain Graphene Grown on Co Film with Polarised Neutron Reflectivity.

In this paper, we determine the magnetic moment induced in graphene when grown on a cobalt film using polarised neutron reflectivity (PNR). A magnetic signal in the graphene was detected by X-ray magnetic circular dichroism (XMCD) spectra at the C K-edge. From the XMCD sum rules an estimated magnetic moment of 0.3 µB/C atom, while a more accurate estimation of 0.49 µB/C atom was obtained by carrying out a PNR measurement at 300 K. The results indicate that the higher magnetic moment in Co is counterbalanced by the larger lattice mismatch between the Co-C (1.6%) and the slightly longer bond length, inducing a magnetic moment in graphene that is similar to that reported in Ni/graphene heterostructures.

Codependencies of mTORC1 signaling and endolysosomal actin structures.

The mechanistic target of rapamycin complex 1 (mTORC1) is part of the amino acid sensing machinery that becomes activated on the endolysosomal surface in response to nutrient cues. Branched actin generated by WASH and Arp2/3 complexes defines endolysosomal microdomains. Here, we find mTORC1 components in close proximity to endolysosomal actin microdomains. We investigated for interactors of the mTORC1 lysosomal tether, RAGC, by proteomics and identified multiple actin filament capping proteins and their modulators. Perturbation of RAGC function affected the size of endolysosomal actin, consistent with a regulation of actin filament capping by RAGC. Reciprocally, the pharmacological inhibition of actin polymerization or alteration of endolysosomal actin obtained upon silencing of WASH or Arp2/3 complexes impaired mTORC1 activity. Mechanistically, we show that actin is required for proper association of RAGC and mTOR with endolysosomes. This study reveals an unprecedented interplay between actin and mTORC1 signaling on the endolysosomal system.

Review: Maintenance of the ruminant corpus luteum during pregnancy: interferon-tau and beyond.

This manuscript reviews the mechanisms that maintain the corpus luteum (CL) of pregnancy in ruminants. In mammals, ovulation and luteinization of the remaining cells in the CL are due to a surge in Luteinizing Hormone (LH). In cattle, continued secretion of pulses of LH is essential for full development and function of the CL during the estrous cycle (LH pulses), however, the few studies on the CL after d20 of pregnancy do not indicate that LH is essential for maintaining the CL of pregnancy. The first essential step in maintaining the CL of pregnancy in ruminants is overcoming the mechanisms that cause regression of the CL in non-pregnant ruminants (d18-25 in cattle; d13-21 in sheep). These mechanisms have a uterine component involving oxytocin-induced prostaglandin F2α (PGF2A) pulses and a luteal component involving decreased progesterone production and luteal cell death. There is a critical role for embryonic interferon-tau (IFNT) in suppressing the uterine secretion of PGF2A during early pregnancy (d13-21 in sheep; d16-25 in cattle) and preventing luteolysis. There are also effects of IFNT on the expression of interferon-stimulated genes in other tissues including the CL but the physiologic role of these interferon-stimulated genes is not yet clear. After the IFNT period, there is another mechanism that maintains the CL of pregnancy in ruminants since embryonic IFNT is inhibited as attachment occurs and trophoblastic binucleate/giant cells begin secretion of pregnancy-associated glycoproteins. The second mechanism for luteal maintenance has not yet been defined but acts in a local manner (ipsilateral to pregnancy), and remains functional from d25 until just before parturition. The most likely mechanisms mediating later maintenance of the CL of pregnancy are increased uterine blood flow or decreased prostaglandin transporter expression in the utero-ovarian vasculature, preventing PGF2A reaching the CL. Finally, implications of these ideas on pregnancy loss in cattle are explored, highlighting the importance of inappropriate regression of the CL of pregnancy as a mechanism for pregnancy loss in cattle.

The vulnerabilities of Venezuelan immigrants in Brazil and Colombia from the perspective of Intervention Bioethics.

OBJECTIVE: To understand the vulnerabilities to which Venezuelan immigrants living in Brazil and Colombia are exposed, from the perspective of Intervention Bioethics. METHOD: Qualitative study, carried out through a semi-structured interview, with 15 immigrants living in Brasília-Brazil and 20 in Medellín-Colombia, analyzed by the IRAMUTEQ software, in the Descending Hierarchical Classification and Similitude Analysis modalities. RESULTS: The first thematic axis dealt with the reasons for immigrating, above all, difficulties in accessing food and health services. The second axis revealed the trajectory of the migration process, especially the adversities faced before arriving in the countries. The third axis highlighted the challenges of integration in the destination countries, with emphasis on the processes of exclusion and discrimination faced. CONCLUSION: It was observed that both Brazil and Colombia need, as proposed by Bioethics of Intervention, to develop policies to reduce the vulnerabilities of immigrants to guarantee a dignified life without discrimination against them.

Research on timed AI in beef cattle: Past, present and future, a 27-year perspective.

This review aimed to (1) summarize the results from fixed-timed artificial insemination (TAI) fertility studies performed during the last 27 years; (2) compile and evaluate, as examples from the literature base, the direct comparisons made of specific manipulations to synchronization protocols; (3) evaluate the impact of the TAI programs on the reproductive performance during the breeding season, and (4) provide perspective on the future of TAI programs in beef cattle. A search of the literature published from 1995 to 2021 was conducted to identify experiments in which synchronization of ovulation and TAI in beef cattle was performed. The primary outcome of interest was fertility expressed as pregnancies per TAI. The literature included two search engines, the SIS Web of Science and the US National Library of Medicine Institutes of Health through PubMed. After the initial search and screening, a total of 228 manuscripts were selected containing a total of 272,668 TAI. A dramatic increase in the number of publications and TAIs occurred throughout the years. Most of them were from Brazil and United States, followed by Canada, Argentina, Uruguay, and Australia. Two main types of TAI programs were identified: GnRH-based and E2/P4-based protocols. In terms of GnRH-based programs, two variations were evaluated in the present manuscript. First, we evaluated the effect of the progesterone implant during the protocol. The progesterone implant increased pregnancy/TAI (P/TAI) from 44.3 to 54.3%. Second, the use of a second prostaglandin F2α treatment in 5-d CO-synch program increased the P/TAI from 53.2 to 60.9%. In E2/P4-based programs, use of GnRH at TAI increased P/TAI from 54.7 to 59.2% in cows. However, no increase was detected in heifers. Other research showed that use of TAI can increase the overall proportion of the cows pregnant at end of the breeding season and produce earlier calvings compared with bulls. In conclusion, there have been a large number of excellent research studies that have been performed during the last 27 years on TAI in beef cattle. This technology is being utilized successfully in the beef cattle industry. This success is largely because of the valid research that underlies the application of the technology and the economic value of the technology.