Information geometry for phylogenetic trees.

We propose a new space of phylogenetic trees which we call wald space. The motivation is to develop a space suitable for statistical analysis of phylogenies, but with a geometry based on more biologically principled assumptions than existing spaces: in wald space, trees are close if they induce similar distributions on genetic sequence data. As a point set, wald space contains the previously developed Billera-Holmes-Vogtmann (BHV) tree space; it also contains disconnected forests, like the edge-product (EP) space but without certain singularities of the EP space. We investigate two related geometries on wald space. The first is the geometry of the Fisher information metric of character distributions induced by the two-state symmetric Markov substitution process on each tree. Infinitesimally, the metric is proportional to the Kullback-Leibler divergence, or equivalently, as we show, to any f-divergence. The second geometry is obtained analogously but using a related continuous-valued Gaussian process on each tree, and it can be viewed as the trace metric of the affine-invariant metric for covariance matrices. We derive a gradient descent algorithm to project from the ambient space of covariance matrices to wald space. For both geometries we derive computational methods to compute geodesics in polynomial time and show numerically that the two information geometries (discrete and continuous) are very similar. In particular, geodesics are approximated extrinsically. Comparison with the BHV geometry shows that our canonical and biologically motivated space is substantially different.

Extemporaneous printing of diclofenac orodispersible films for pediatrics.

OBJECTIVE: The possible application of a hot-melt ram extrusion printing to the preparation of diclofenac orodispersible films (ODF) made of maltodextrin was studied focusing the attention on the effects of taste-masking agents (i.e. namely mint, licorice-mint, and sucralose) and an opacifier (titanium dioxide [TiO2]). SIGNIFICANCE: This is a proof-of-concept of the feasibility to print ODF loaded with a thermosensitive drug substance by hot-melt technologies. METHODS: Diclofenac sodium (DNa) ODF made of maltodextrin (dextrose equivalent (DE) = 6 ) plasticized with glycerol were prepared by hot-melt extrusion printing. ODF were characterized for disintegration time, drug content, and solid state, in vitro dissolution in deionized water and simulated salivary fluid at pH 5.7, tensile, and adhesive properties. Moreover, the stability of ODF was assessed in accelerated conditions over six months. RESULTS: After the preparation, no variation in drug solid state was evident and the formation of impurity A of DNa was detected, even if it remained below the Pharmacopoeia (Ph. Eur.) limits (< 0.2%). Only the addition of DNa significantly improved the ODF tensile properties: the tensile strength increased from 0.17 ± 0.03 MPa (placebo ODF) to 2.21 ± 0.54 MPa (p ≤ 0.03). All ODF disintegrated in about 1 min, and the t80% was lower than 3 min. TiO2 reduced the static and dynamic peel forces (p ≤ 0.006) favoring the ODF detachment from the primary packaging material. During the accelerated stability study, ODF were easy to handle without fracture; the drug content, impurity A, and dissolution profiles remained superimposable. CONCLUSION: Hot-melt printing can be suitable to prepare palatable ODF loaded with bitter thermosensitive drugs.

Patterns and drivers of genetic diversity and structure in the biological control parasitoid Habrobracon hebetor in Niger.

When a promising natural enemy of a key pest exists locally, it is a common practice in biological control (BC) to rear and release it for supplementary control in the targeted agroecosystem even though significant knowledge gaps concerning pre/post release may still exist. Incorporating genetic information into BC research fills some of these gaps. Habrobracon hebetor, a parasitoid of many economically important moths that infest stored and field crops worldwide is commonly used, particularly against the millet head miner (MHM), a key pest of millet in Sahelian countries. To advance our knowledge on how H. hebetor that occurs naturally in open-field cropping systems and grain stores as well as being mass-produced and released for MHM control, performs in millet agroecosystems in Niger we evaluated its population genetics using two mitochondrial and 21 microsatellite markers. The field samples were genetically more diverse and displayed heterozygote excess. Very few field samples had faced significant recent demographic bottlenecks. The mating system (i.e. nonrandom mating with complementary sex determination) of this species may be the major driver of these findings rather than bottlenecks caused by the small number of individuals released and the scarcity of hosts during the longlasting dry season in Niger. H. hebetor population structure was represented by several small patches and genetically distinct individuals. Gene flow occurred at local and regional scales through human-mediated and natural short-distance dispersal. These findings highlight the importance of the mating system in the genetic diversity and structure of H. hebetor populations, and contribute to our understanding of its reported efficacy against MHM in pearl millet fields.

Preterm birth in the first pregnancy and risk of neonatal death in the second pregnancy: a propensity score-weighted matching approach.

The study purpose was to assess the relationship between various grades of preterm birth (moderate preterm: 33-36 weeks; severe preterm: 27-32 weeks; extreme preterm: ≤ 26 weeks) in the first pregnancy and neonatal mortality (death within 28 days of birth; early: 0-7 days; late: 8-28 days) in the second pregnancy. Using the Missouri maternally-linked dataset (1989-2005), a population-based, retrospective cohort analysis with propensity score-weighted matching was conducted on mothers with two consecutive singleton live births (n = 310,653 women). Women with a prior preterm birth were more likely to subsequently experience neonatal death. The odds increased in a dose-dependent pattern with ascending severity of the preterm event in the first pregnancy (moderate preterm: AOR = 1.32; 95% CI: 1.10-1.60; severe preterm: AOR = 2.62; 95% CI: 2.01-3.41; extreme preterm: AOR = 5.84; 95% CI: 4.28-7.97; p value for trend < 0.001). However, the pathway for the relationship between prior preterm birth and subsequent neonatal mortality may be the recurrence of preterm birth.

Awareness, use, and unmet need for family planning in rural northern Nigeria.

Access to quality reproductive health and family planning services remain poor in Nigeria. We present results on family planning awareness and use from a survey of 3,080 women (age 15-49 years) in Jigawa, Katsina, Yobe, and Zamfara States. About 43.0% had heard of any method of contraception whereas 36.6% had heard of any modern method. Overall, 7.0% of all currently married women reported ever using a method of contraception; 4.4% used a modern method and 2.9% used a traditional method. Only 1.3% of women in union (currently married or cohabiting) used modern contraception methods at the time of the survey; 1.3% of women in union used traditional methods. Unmet need for family planning was 10.3%. Low family planning use in the presence of low awareness and low felt need suggests, among other things, a need to increase awareness and uptake and make family planning commodities available.

Drug-Eluting Sutures by Hot-Melt Extrusion: Current Trends and Future Potentials.

Surgical site infections (SSIs) may result from surgical procedures requiring a secondary administration of drugs at site or systemically in treating the infection. Drug-eluting sutures containing antimicrobial agents symbolise a latent strategy that precludes a secondary drug administration. It also offers the possibility of delivering a myriad of therapeutic agents to a localised wound site to effect analgesia, anti-inflammation, or the deployment of proteins useful for wound healing. Further, the use of biodegradable drug-eluting sutures eliminates the need for implanting foreign material into the wound, which needs to be removed after healing. In this review, we expound on recent trends in the manufacture of drug-eluting sutures with a focus on the hot-melt extrusion (HME) technique. HME provides a solvent-free, continuous one-step manufacturing conduit for drug-eluting sutures, hence, there is no drying step, which can be detrimental to the drug or suture threads and, thus, environmentally friendly. There is the possibility of combining the technology with additive manufacturing platforms to generate personalised drug-loaded implantable devices through prototyping and scalability. The review also highlights key material requirements for fabricating drug-eluting sutures by HME, as well as quality attributes. Finally, a preview of emerging drug-eluting sutures and advocacy for harmonisation of quality assurance by regulatory authorities that permits quality evaluation of novelty sutures is presented.

Assessment of the impact of crop management strategies on the yield of early-maturing maize varieties in the drylands of Niger Republic: Application of the DSSAT-CERES-Maize model.

Maize is increasingly becoming important in Niger for use as food and feed. Production is however, faced with several abiotic and biotic constraints. Researchers have developed early-maturing maize varieties that are tolerant to drought, the parasitic weed Striga hermonthica and diseases that fit into the short growing production environment. The evaluation and deployment of these varieties would, however, involve costly and time-consuming field trials across the maize production zones of the country. The CERES-Maize model was applied to assess the performance of two early-maturing maize varieties under varying planting windows and nitrogen application in three agroecological zones of the country. The model was calibrated with datasets collected from field trials conducted under optimal conditions (supplementary irrigation and full nutrient supply) at three locations in northern Nigeria. The model was validated with independent data set obtained from field trials conducted in 2020 and 2021 at 4 locations in the Republic of Niger under rainfed conditions. For each variety the treatments were five nitrogen (N) rates (0, 30, 60, 90 and 120 kg ha-1). The results from model calibration and validation revealed that the model accurately reproduced the observed value for days to flowering, physiological maturity, aboveground dry biomass and grain yield with low nRMSE (0.4-12.7%) and high d-index (0.70-0.99) for both varieties. The long-term simulation results (1985-2020) showed that the maize performance was dependent on location, planting window and nitrogen rates. The variety 2014 TZE-Y yielded higher than Brico in all locations for all treatments because it takes longer to mature and accumulate higher dry matter and have higher number of kernels. Simulated yields were generally higher in the Sudan savanna agroecological zone than in the other zones because of higher rainfall and higher clay content of the soil in this zone. The response to N application was influenced by planting window in each agroecological zone. With the exception of two sites, grain yield declined with planting beyond July 14 (PW3) and response to N was not significant beyond this date in the Sudan savanna agroecological zone. Grain yield declined with planting beyond July 7 in the Sahel and Sudan Sahel agroecological zones. There was no further response to N beyond 30 and 60 kg N ha-1 when planting is delayed beyond July 7 in the Sahel and Sahel-Sudan agroecological zones, respectively.

The International Natural Product Sciences Taskforce (INPST) and the power of Twitter networking exemplified through #INPST hashtag analysis.

BACKGROUND: The development of digital technologies and the evolution of open innovation approaches have enabled the creation of diverse virtual organizations and enterprises coordinating their activities primarily online. The open innovation platform titled "International Natural Product Sciences Taskforce" (INPST) was established in 2018, to bring together in collaborative environment individuals and organizations interested in natural product scientific research, and to empower their interactions by using digital communication tools. METHODS: In this work, we present a general overview of INPST activities and showcase the specific use of Twitter as a powerful networking tool that was used to host a one-week "2021 INPST Twitter Networking Event" (spanning from 31st May 2021 to 6th June 2021) based on the application of the Twitter hashtag #INPST. RESULTS AND CONCLUSION: The use of this hashtag during the networking event period was analyzed with Symplur Signals (https://www.symplur.com/), revealing a total of 6,036 tweets, shared by 686 users, which generated a total of 65,004,773 impressions (views of the respective tweets). This networking event's achieved high visibility and participation rate showcases a convincing example of how this social media platform can be used as a highly effective tool to host virtual Twitter-based international biomedical research events.

Solid Dispersion Formulations by FDM 3D Printing-A Review.

Additive manufacturing (AM) is revolutionizing the way medicines are designed, manufactured, and utilized. Perhaps, AM appears to be ideal for the fit-for-purpose manufacturing of medicines in contrast to the several disadvantages associated with the conventional fit-for-all mass production that accounts for less than 50% of pharmacotherapeutic treatment/management of diseases especially among children and elderly patients, as well as patients with special needs. In this review, we discuss the current trends in the application of additive manufacturing to prepare personalized dosage forms on-demand focusing the attention on the relevance of coupling solid dispersion with FDM 3D printing. Combining the two technologies could offer many advantages such as to improve the solubility, dissolution, and oral bioavailability of poorly soluble drugs in tandem with the concept of precision medicine and personalized dosing and to address the dilemma of commercial availability of FDM filaments loaded with Class II and/or Class IV drugs. However, thermal treatment especially for heat-sensitive drugs, regulatory, and ethical obligations in terms of quality control and quality assurance remain points of concern. Hence, a concerted effort is needed between the scientific community, the pharmaceutical industries, the regulatory agencies, the clinicians and clinical pharmacists, and the end-users to address these concerns.

Falsified and substandard medicines trafficking: A wakeup call for the African continent.

While great effort is being placed on reducing disease burdens in Africa, the circulation of falsified and substandard medicines in the continent are reversing the hard-won gains. This commentary provides insights on the high (and increasing) burden, impact and threat that falsified and substandard medicines pose to the region's development. The proposed recommendations, such as a coherent multi-sectorial and government-led strategy, call for a fundamental rethink of approaches towards strong regulations, policies, legislations, community-based approaches, collaborations and investments, which all must be scaled up before this the situation gets out of control. These recommendations are of paramount importance and have the potential to ensure access to genuine medicines and also to avert therapeutic failure and intoxication from dangerous substances. In addition, there will be added benefits to the economic, social, health and well-being of the region. Concerted efforts towards medicine regulations have enormous potential to contribute towards averting many preventable deaths and reducing disease burden in the region. A paradigm shift is necessary to ensure quality medicines reach patients at community and healthcare facilities to prevent this silent epidemic in Africa.

Twitter-based crowdsourcing: What kind of measures can help to end the COVID-19 pandemic faster?

Background: Crowdsourcing is a low-cost, adaptable, and innovative method to collect ideas from numerous contributors with diverse backgrounds. Crowdsourcing from social media like Twitter can be used for generating ideas in a noticeably brief time based on contributions from globally distributed users. The world has been challenged by the COVID-19 pandemic in the last several years. Measures to combat the pandemic continue to evolve worldwide, and ideas and opinions on optimal counteraction strategies are of high interest. Objective: This study aimed to validate the use of Twitter as a crowdsourcing platform in order to gain an understanding of public opinion on what measures can help to end the COVID-19 pandemic faster. Methods: This cross-sectional study was conducted during the period from December 22, 2021, to February 4, 2022. Tweets were posted by accounts operated by the authors, asking "How to faster end the COVID-19 pandemic?" and encouraging the viewers to comment on measures that they perceive would be effective to achieve this goal. The ideas from the users' comments were collected and categorized into two major themes - personal and institutional measures. In the final stage of the campaign, a Twitter poll was conducted to get additional comments and to estimate which of the two groups of measures were perceived to be important amongst Twitter users. Results: The crowdsourcing campaign generated seventeen suggested measures categorized into two major themes (personal and institutional) that received a total of 1,727 endorsements (supporting comments, retweets, and likes). The poll received a total of 325 votes with 58% of votes underscoring the importance of both personal and institutional measures, 20% favoring personal measures, 11% favoring institutional measures, and 11% of the votes given just out of curiosity to see the vote results. Conclusions: Twitter was utilized successfully for crowdsourcing ideas on strategies how to end the COVID-19 pandemic faster. The results indicate that the Twitter community highly values the significance of both personal responsibility and institutional measures to counteract the pandemic. This study validates the use of Twitter as a primary tool that could be used for crowdsourcing ideas with healthcare significance.

Maternal mortality in Niger: a retrospective study in a high risk maternity.

OBJECTIVE: This study analyzes maternal deaths in a tertiary maternity in Niamey, Niger. METHODS: This is a retrospective study covering the period of one year, from January 1 to December 31 2007. The setting for this study was the Maternity Issaka Gazobi, a tertiary maternity referral centre in the city of Niamey, Niger. Data encompasses all hospital maternal deaths attributable to obstetric causes. The data were abstracted from emergency room, delivery rooms and hospitalization units' patient files. RESULTS: During the study period a total of 4,582 live births were registered with a total count of 121 maternal deaths, yielding a maternal mortality ratio of 2,640/100,000 live births. The mean age of deceased mothers was 26 years with a range of 15 to 43 years, and 46% of them were 15-24 years old. The most common risk factors for maternal death were primiparity (33%), haemorrhage (30%) and anaemia (22%). Most of the maternal deaths occurred post-partum (70%), 24 died peripartum, 6 died from miscarriage or abortion in association with excessive bleeding or septic complications, and one died from etopic pregnancy. Among most deaths, the burden of morbidity was important, with 57.9% of patients admitted in a state of shock from eclampsia or acute cerebral malaria. CONCLUSIONS: The high rate of mortality in this hospital testifies to the high morbidity of the patients, with anemia as an important risk factor. Maternal mortality in Niger remains high due to socio-economic factors, lack of access to quality care, and insufficient number of qualified health personnel.

Prevalence and Impacts of Psychoactive Substance Abuse amongst Undergraduate University Students in Katsina State, Nigeria.

BACKGROUND: Drug and substance abuse among university students is of public health concern and is becoming a global threat to the education system. This is more devastating to the academic performance of the addicts. The present study aims to assess the prevalence and impacts of psychoactive substance abuse among the university undergraduate students in Katsina State, Nigeria, and to determine the effects of such abuses on the students' academic performance. METHODS: A cross-sectional study was conducted using online survey tool (Google Form) validated by content validity and pilot study. The hyperlink to the online survey tool was shared with undergraduate students from three universities located in Katsina State via emails and social media platforms, namely WhatsApp, Facebook, and Twitter. Data collected from eligible participants were analyzed using descriptive statistics. FINDINGS: A total of 308 students from the three universities returned the online questionnaire, of which 67.2% were men and 32.8% were women. Among the respondents, 37% admitted practicing drug and/or substance abuse. Majority of them (56.2%) were third-year students in the age range of 20-25 years. CONCLUSION: Drug and substance abuse among the undergraduate university students in Katsina State is common, and it cuts across both male and female students. Concerted efforts towards parental support and supervisions, social intervention programs, and campus-based prevention and supported programs against drug and substance abuse should be encouraged.

Review of pharmacologic and immunologic agents in the management of COVID-19.

The novel coronavirus disease 2019 (COVID-19) is the third coronavirus outbreak in the last two decades. Emerging and re-emerging infections like COVID-19 pose serious challenges of the paucity of information and lack of specific cure or vaccines. This leaves utilisation of existing scientific data on related viral infections and repurposing relevant aetiologic and supportive therapies as the best control approach while novel strategies are developed and trialled. Many promising antiviral agents including lopinavir, ritonavir, remdesivir, umifenovir, darunavir, and oseltamivir have been repurposed and are currently trialled for the care for COVID-19 patients. Adjunct therapies for the management of symptoms and to provide support especially in severe and critically ill patients have also been identified. This review provides an appraisal of the current evidence for the rational use of frontline therapeutics in the management of COVID-19. It also includes updates regarding COVID-19 immunotherapy and vaccine development.

Relevance of production method on the physical stability and in vitro biopharmaceutical performances of olanzapine orodispersible film.

This study assessed the relevance of the preparation process, namely solvent casting and hot-melt ram printing, on the biopharmaceutical performances of olanzapine orodispersible films (ODF) made of maltodextrins. Beside the clinical rationale, olanzapine was selected since it is subjected to polymorphism which impacts on its bioavailability. All ODF disintegrated in less than 3 min and showed content uniformity within the acceptable values. Dissolution testing in 3 mL of artificial saliva at pH = 6.8 evidenced that cast and printed ODF released after 5 min about 2% and 100%, respectively; at higher volume, a yellow precipitate was formed after disintegration of the cast ODF. At pH = 1.2, the t85% for cast ODF was reached after about 20 min and only the 90% olanzapine was dissolved increasing the pH to 6.8. These differences were explained by DSC, TGA and X-ray diffraction data which demonstrated that the casting method, which included the preparation of an aqueous slurry, favours the conversion from Form I to a hydrated one. Since extruded ODF resulted physically stable after 30 months, this suggests the potentiality of this technique to load in ODF drugs undergoing solid-state modification after exposure to aqueous media.

Trends in the Characterization Methods of Orodispersible Films.

The recent increased interest in orodispersible films (ODF) stems from their ideal potential to circumvent several pharmacotherapy-related problems, such as improved medication compliance and adherence, especially in children, elderly and uncooperative patients. Their administration is well accepted by the majority of patients because ODF dissolve upon contact with the saliva in the oral cavity without the need for water intake. ODF application in personalized pharmacotherapy is currently being exploited. Moreover, innovative preparation methods and characterization technologies have been evolving in recent years, highlighting a promising future both from the technological and clinical standpoints. However, the key obstacles to the attainment of full potential of ODF in the pharmaceutical field is the lack of harmonized and well-defined quality characterization procedures, standard evaluation parameters, guidance on appropriate final product properties and specifications. This review provides an appraisal on the ODF characterization methods from slurries to the finished medicinal products with a specific focus on the technologies suitable for identification, quantification, and quality evaluation of extemporaneously prepared ODF on small batches in individualized pharmacotherapy. Generally, there is a paradigm shift from the use of the conventional quality evaluation tools and/or protocols for oral solid dosage forms to characterize ODF to more specific equipment and procedures that suit the peculiarities of the ODF.

Mental health in Nigeria: A Neglected issue in Public Health.

In Nigeria, the disparity between available healthcare services and need for mental health services is palpable. Although, the country has made significant advances on challenging public health problems, health-related policy development and legislation in trying to achieve health for all policy, there have been challenges with regards to mental health services including that of policy development and legislation, financing, research, training and integration of mental health care into primary health care. We consulted relevant publications, official document, policy statement, blueprints, working plans of the relevant organizations responsible for mental care and services locally and globally. We identify and highlight challenges faced in mental health services implementation and provide recommendations as way forward and call for urgent action to government, non-governmental organizations (NGOs), policy makers and legislatives which are urgently needed to reform and implement them for a better, accessible, and affordable mental health services for the mental well-being of the populace.

The influence of Nifadin, Niprisan and Niprd/92/001/1-1 (AM-1) on the pharmacokinetics of metronidazole in rats.

The single oral dose pharmacokinetics of metronidazole was studied alone and after co-administration with phytomedicines, Nifadin, Niprisan and Niprd/92/001/1-1 (AM-1), in rats. Plasma metronidazole concentrations were measured using high-performance liquid chromatography method developed earlier in our laboratory. The data were fitted into a WinNonlin standard non-compartmental programme. The co-administration of the herbal medicines with metronidazole produced an increase in the serum concentration of metronidazole at each sampling time. The highest increase of 184% occurring at the time of peak concentration (1 h) was obtained with AM-1, followed by 145% with Niprisan, the least was 131% with Nifadin. Significant increase was also observed in some other parameters, such as area under the serum concentration-time curve (AUC0-24) and maximum serum concentration (Cmax), while the apparent volume of distribution (Vd) and plasma clearance (C1) reduced significantly (P < 0.05). It was concluded that the gastric presence of the herbal medicines impaired the absorption and elimination Niadin alone) of metronidazole in rats significantly (P < 0.05).

Trends in the production methods of orodispersible films.

Interest in orodispersible films (ODF) is growing day-by-day, since this dosage form overcomes some therapeutic obstacles, such as impaired swallowing, and offers several benefits, such as the possibility to adapt the dosing requirements for a subset of patients. As a consequence, technologies to produce ODF have risen attention for possible applications in the development of patient-centric formulations. This review critically discusses current trends in the technology platforms proposed to manufacture ODF, including the innovation and opportunities to produce very small batches in a pharmacy setting. Although the main Pharmacopoeias recommend testing customized dosage forms for quality assurance, pharmaceutical assays are a matter of debate due to the complexity and high cost of conventional methods. Alternatively, non-disruptive online analytic methods can be proposed to assay ODF properties, above all to assure the uniformity of drug content.

Assessment of occupational violence towards pharmacists at practice settings in Nigeria.

BACKGROUND: Occupational Violence is prevalent among healthcare workers, including pharmacists, and poses a big threat to their job satisfaction, safety, and social wellbeing. OBJECTIVE: This study seeks to assess the incidents and factors associated with occupational violence towards pharmacists in Nigeria. METHODS: A cross-sectional study was conducted among pharmacists practicing in Nigeria, using an online survey (Google Form™). Occupational violence was assessed using a validated questionnaire. The survey was conducted and reported based on the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). Participants were recruited by sharing the survey link via social media platforms including WhatsApp, Facebook, LinkedIn, and Twitter. RESULTS: A total of 263 respondents returned the online questionnaire, with a completion rate of 99.2%. The prevalence of occupational violence was 92.7% (95% CI, 90 to 96). Violent events occurred among 48.7% of pharmacists with at least six years of experience, and 68.4% of hospital pharmacists. The commonly reported factors associated with the violence include long waiting times in the pharmacy (36.5%), refusal to fulfil aggressor's demands (22.1%), and counseling/poor communication (21.7%). Events related to verbal abuse were reported among 95% of the participants. The prevalence of violence was significantly higher among hospital pharmacists, compared with those practicing in administration/regulatory, and in community pharmacies (chi-square=10.213 (2); p=0.006). Similarly, physical aggression was higher among hospital pharmacists (chi-square=10.646 (2), p = 0.005). CONCLUSIONS: The prevalence of occupational violence towards pharmacists practicing in Nigeria appeared to be high. Major factors associated with the violence were refusal to fulfil aggressors' demands and frustrations due to long waiting times at pharmacy. Recommended strategies to slowdown the incidences of violence were improved pharmacists' workforce, interprofessional harmony, and penalties against perpetrators.