Childhood cancer incidence & survival in Aotearoa, New Zealand 2010-2019.

OBJECTIVE: To provide updated estimates of childhood cancer incidence and survival in Aotearoa, New Zealand. METHOD: Registrations for children under the age of 15 years diagnosed with cancer between 2010 and 2019 were extracted from the New Zealand Children's Cancer Registry. Cases were stratified by age, sex, prioritised ethnicity (Maori, Pacific peoples, and non-Maori) and cancer type. Age-standardised incidence rates (ASRs) per million person years and observed survival rates were calculated. RESULTS: During the study period, 1522 children were diagnosed with cancer providing an ASR of 169.1 per million per year (95 % Confidence Interval, CI: 157.0-181.2). For all childhood cancers combined, survival at 5-years was 85.6 % (95 % CI 83.7-87.3). There was a gap in 5-year survival between Maori (80.9 %, 95 % CI 76.5-84.6), Pacific peoples (82.6 %, 95 % CI 75.6-87,7) and Non-Maori (87.8 %, 95 % CI 85.6-89.7) In both adjusted and unadjusted models, this difference in survival was most marked (p < 0.05) among children who were 10-14 years of age at diagnosis. CONCLUSION: Childhood cancer incidence and survival rates in Aotearoa, New Zealand remain comparable to other high-income countries. Further research is required to understand the survival difference between ethnic groups.

Outcomes of rapid digital transformation of large-scale communications during the COVID-19 pandemic.

Objective This study examined the content and impact of a new digital communication medium, called a VIDCAST, implemented at a large hospital and health service when the COVID-19 pandemic was announced, and the key concerns held by staff at the time when the health service was preparing for the COVID-19 pandemic to arrive in this health service. Methods A mixed-methods approach was used. Thematic analysis of 20 transcripts of daily VIDCASTS broadcast between 30 March and 24 April 2020 was undertaken, in addition to descriptive analysis of feedback from an anonymous online survey. Results Survey feedback from 322 staff indicated almost universal satisfaction with this new communication method. The VIDCASTS provided a new COVID-safe method for the Executive to connect to staff at a time of uncertainty. Thematic analysis of the content of the VIDCASTS revealed three themes: 'Accurate Information', 'Reassurance and Support' and 'Innovation'. The Executive was able to reassure staff about what the organisation was doing to safeguard the health and wellbeing of all, and enabled an effective response to the pandemic. Conclusions The digital communication channel of VIDCASTS, rapidly operationalised at a major Australian hospital and health service in March 2020, provided important information and support for staff as it prepared for the anticipated COVID-19 surge. What is known about the topic? When the COVID-19 pandemic began, traditional face-to-face staff meetings were disrupted and many hospitals and their staff were left scrambling for information, and for reassurance about their safety, as they prepared to receive increasing numbers of COVID-19 patients. What does this paper add? The implementation of a digital communication tool was able to address many of the concerns raised by hospital staff in other geographic locations dealing with surging COVID-19 cases and underpinned a globally leading COVID-19 response. What are the implications for practitioners? New digitised communication methods provided an effective vehicle to inform and support staff in the early stages of pandemic preparation.

Automated Cerebral Hemorrhage Detection Using RAPID.

BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) is an important event that is diagnosed on head NCCT. Increased NCCT utilization in busy hospitals may limit timely identification of ICH. RAPID ICH is an automated hybrid 2D-3D convolutional neural network application designed to detect ICH that may allow for expedited ICH diagnosis. We determined the accuracy of RAPID ICH for ICH detection and ICH volumetric quantification on NCCT. MATERIALS AND METHODS: NCCT scans were evaluated for ICH by RAPID ICH. Consensus detection of ICH by 3 neuroradiology experts was used as the criterion standard for RAPID ICH comparison. ICH volume was also automatically determined by RAPID ICH in patients with intraparenchymal or intraventricular hemorrhage and compared with manually segmented ICH volumes by a single neuroradiology expert. ICH detection accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratios by RAPID ICH were determined. RESULTS: We included 308 studies. RAPID ICH correctly identified 151/158 ICH cases and 143/150 ICH-negative cases, which resulted in high sensitivity (0.956, CI: 0.911-0.978), specificity (0.953, CI: 0.907-0.977), positive predictive value (0.956, CI: 0.911-0.978), and negative predictive value (0.953, CI: 0.907-0.977) for ICH detection. The positive likelihood ratio (20.479, CI 9.928-42.245) and negative likelihood ratio (0.046, CI 0.023-0.096) for ICH detection were similarly favorable. RAPID ICH volumetric quantification for intraparenchymal and intraventricular hemorrhages strongly correlated with expert manual segmentation (correlation coefficient r = 0.983); the median absolute error was 3 mL. CONCLUSIONS: RAPID ICH is highly accurate in the detection of ICH and in the volumetric quantification of intraparenchymal and intraventricular hemorrhages.

A comparison of parent and childcare provider's attitudes and perceptions about preschoolers' physical activity and outdoor time.

BACKGROUND: Young children depend on adult caregivers to provide opportunities for physical activity. Research has focused on barriers and facilitators to children's physical activity while in childcare, but parental influences remain largely unknown. This study examines parent's attitudes about preschoolers' physical activity and outdoor time, compares them with those of childcare providers and determines the association between parental attitudes and preschoolers' measured activity. METHODS: Parents and childcare providers from 30 childcare centres were surveyed regarding attitudes towards preschoolers' physical activity and outdoor time. Children's moderate-to-vigorous physical activity was determined by using 24-h accelerometry. Parent and childcare providers' responses were compared. Mixed-effect linear regression examined moderate-to-vigorous physical activity and sedentary time as outcomes with parental attitudes as predictors, family demographics as covariates and centre as a random effect. RESULTS: Three hundred eighty-eight parents and 151 childcare providers participated. On average, children were 4.3 (0.7) years old. Parents and childcare providers both considered daily physical activity important for preschoolers, but providers rated the importance of daily outdoor time higher on a 10-point scale (8.9 vs. 7.6, P < 0.001). More parents than providers believed that children would get sick by playing outside in the cold (25 vs. 11%, P < 0.05). Parents were more comfortable with their child playing outside at childcare compared with outside at home (8.9 vs. 6.9, P < 0.001). Lower income parents felt less comfortable than higher income parents with their child playing outside either near home or at childcare. Neither home nor total child activity levels were associated with most parental attitudes queried. CONCLUSIONS: While parents and childcare providers value daily physical activity for children, some parents expressed discomfort about their young children engaging in outdoor play, especially around home and in cold weather. These findings highlight the importance of childcare-based interventions to promote preschoolers' physical activity and outdoor play.

Association of childcare arrangement with overweight and obesity in preschool-aged children: a narrative review of literature.

The time children spend in childcare overlaps with daily meals and opportunities to be active. Thus these environments have the opportunity to promote-or hinder-healthy weight gain among children who attend them. The purpose of this narrative review was to compile findings from studies examining childcare type and weight outcomes among preschool-age children. A literature search was conducted using PubMed, PsychInfo and ERIC. Inclusion criteria were infant- to 5-year-old children exposed to any type of childcare with a cross-sectional or longitudinal weight outcome. Among 385 studies screened, 18 were included. For comparison across studies, type of childcare was categorized as: childcare center, Head Start, nanny/babysitter, non-relative care/family childcare home and relative care. Four studies found no association with childcare type and obesity, and 10 studies reported mixed results by type of care or subpopulation analyses. Two studies found an overall positive association, and two reported an inverse association. There were differences in direction of associations and findings by type of care arrangement. For Head Start, three of eight studies demonstrated a negative relationship with obesity; none demonstrated a positive association. No other childcare type demonstrated this inverse association. Informal types of care (relative and non-relative care in a home) were positively associated with child obesity in 3 of 10 studies. This association was less commonly reported among formal childcare centers (2 of 15 studies). The majority of studies, however, reported mixed findings or no association by childcare type. Results suggested no consistent evidence for a relationship between childcare and obesity risk, except Head Start. This review exposed the need for a consistent definition of childcare type and the exploration of unmeasured confounders, such as the nutrition and physical activity environment of childcare settings, to understand how they contribute to or protect against the development of overweight/obesity among children.

Placental transfusion strategies in extremely preterm infants: the next piece of the puzzle.

Evidence is growing on the potential value of enhancing placental-fetal transfusion at birth, with recent endorsement of the practice by the World Health Organization and American College of Gynecologists. However, these recommendations provide clinicians with little guidance on the optimal practice among infants born extremely premature (<28 weeks gestation) and those requiring immediate resuscitation. The goals of this review are to: 1) provide rationale for better outcomes among extremely preterm infants following delayed cord clamping or umbilical cord "milking" than with immediate cord clamping; 2) describe clinical situations that warrant immediate cord clamping following delivery and explore the controversy regarding optimal cord clamping practice among extremely premature infants, including those requiring immediate resuscitation; 3) discuss the quality of evidence in this subgroup of infants; 4) consider areas for future research, with a focus on characterizing if placental-fetal transfusion affects the magnitude or timing of variables associated with physiological transition. The review provided herein suggests that delayed cord clamping or umbilical cord milking can be applied safely to infants born prior to 28 weeks gestation, but the lack of evidence on the best practice among infants born severely depressed and requiring immediate resuscitation, who comprise a greater proportion of infant deliveries at the lowest gestational ages, is recognized. Future studies using well-defined physiologic outcome measures are needed to understand the role of placental transfusion in premature infants' adaptations to extrauterine life.

Properties of HTLV-I transformed CD8+ T-cells in response to HIV-1 infection.

HIV-1 infection studies of primary CD8(+) T-cells are hampered by difficulty in obtaining a significant number of targets for infection and low levels of productive infection. Further, there exists a paucity of CD8-expressing T-cell lines to address questions pertaining to the study of CD8(+) T-cells in the context of HIV-1 infection. In this study, a set of CD8(+) T-cell clones were originated through HTLV-I transformation in vitro, and the properties of these cells were examined. The clones were susceptible to T-cell tropic strains of the virus and exhibited HIV-1 production 20-fold greater than primary CD4(+) T-cells. Productive infection resulted in a decrease in expression of CD8 and CXCR4 molecules on the surface of the CD8(+) T-cell clones and antibodies to these molecules abrogated viral binding and replication. These transformed cells provide an important tool in the study of CD8(+) T-cells and may provide important insights into the mechanism(s) behind HIV-1 induced CD8(+) T-cell dysfunction.

Microvascular free tissue transfer for gene delivery: in vivo evaluation of different routes of plasmid and adenoviral delivery.

Transfer of healthy autologous tissue as a microvascular free flap facilitates reconstruction during ablative cancer surgery. In addition to filling surgical defects, free flaps might concentrate viral vectors at the tumour bed and mediate local therapeutic effects. We evaluated the magnitude, topography and duration of luciferase gene expression after plasmid and adenoviral delivery in rat superficial inferior epigastric (SIE) flaps. For plasmid delivery, luciferase expression was significantly increased by all transduction routes (topical, intraflap injection, intravascular) (P<0.01) at day 1, but not at day 7. The spread of luciferase expression was significantly different between the 4 groups at 1 day (P=0.026) and was greatest for flaps transduced by intravascular injection. For adenoviral transduction, total radiance was significantly different between the transduced groups at 1, 14 and 28 days (P<0.05 for all comparisons). The highest levels of radiance were seen in the intravascular group. There was a statistically significant difference in the spread of light emission between the 3 groups at 1 (P=0.009) and 14 (P=0.013) days, but this was no longer evident at 28 days. Intravascular adenoviral delivery yields high-level, diffuse and durable gene expression in rat SIE flaps and is suitable for examination in therapeutic models.

Modulation of HIV-1 transcription by cytokines and chemokines.

Infection with HIV results in the modulation of circulating levels of many host factors. Several host proteins that are up-regulated in HIV infection have the potential to influence virus replication. More specifically, the transcription of HIV-1 can be modulated in vivo by host proteins, including cytokines and chemokines. Cytokines modulate transcription mediated by the HIV-1 long terminal repeat (LTR) via multiple signal transduction pathways with resulting recruitment of numerous transcription factors, including NFkappaB, C/EBP, AP-1, TCF-1alpha, NF-IL-6 and ISGF-3. The effects on transcription may vary depending upon the cell type studied and upon the timing of the exposure of infected or transfected cells to cytokines. Furthermore, studies of cytokine mediated activation or inhibition of LTR mediated transcription may also be affected by the presence of the HIV-1 trans-activating protein, Tat, which has significant impact upon the redox state of the cell. This review will examine the complexities of the positive and negative control of HIV transcription by cytokines and chemokines.

Functional chimeras of human immunodeficiency virus type 1 Gp120 and influenza A virus (H3) hemagglutinin.

In an attempt to produce a protein that will allow determination of the native human immunodeficiency virus type 1 (HIV-1) gp120 (Env) structure in its trimeric state, we fused the globular head of gp120 to the stalk region of influenza virus A (X31) hemagglutinin (HA). The chimeric protein (EnvHA) has been expressed by using a recombinant vaccinia virus system, and its functional characteristics were determined. EnvHA is expressed as a 120- to 150-kDa protein that can oligomerize to form dimers and trimers. It retains the low-pH (5.2 to 5.4) requirement of X31-HA to trigger membrane fusion but, unlike X31-HA, it is not absolutely dependent on exogenously added trypsin for protein processing to release the HA2 fusion peptide. In terms of receptor binding the chimeric protein retains specificity for human CD4 but, in relation to the membrane fusion event, it appears to lose the Env coreceptor specificity of the parental HIV-1 strains: NL43 for CXCR4 and JRFL for CCR5. These properties suggest that stable, functional EnvHAs are being produced and that they may be exploited in terms of structural studies. Further, the potential of introducing the envHA genes into influenza viruses, by use of reverse genetics, and their use as a therapeutic vaccine for HIV are discussed.

World-wide radiation dosage calculations for air crew members.

A greatly improved version of the computer program to calculate radiation dosage to air crew members is now available. Designated CARI-6, this program incorporates an updated geomagnetic cutoff rigidity model and a revision of the primary cosmic ray spectrum based on recent work by Gaisser and Stanev (1998). We believe CARI-6 provides the most accurate available method for calculating the radiation dosage to air crew members. The program is now utilized by airline companies around the world and provides unification for subsequent world-wide studies on the effects of natural radiation on aircrew members.

The role of CD8+ T cell soluble factors in human immunodeficiency virus infection.

Cell-mediated immune responses are important for the control of HIV replication in vivo. Cytotoxic CD8+ T cells (CTL) recognize and kill HIV-infected cells which display MHC class-I proteins. In addition to the recognition and killing of infected cells, CD8+T cells can interfere with stages of the HIV life-cycle. Chemokines produced by CD8+ T cells bind to their seven-transmembrane G protein-coupled receptors resulting in a block in the entry of HIV into macrophages and T cells. In addition, activated CD8+ T cells produce factors which strongly modulate HIV at the level of transcription. This review will focus primarily on the current knowledge of the multifactorial functions of CD8+ T cells in HIV infection. An understanding of the mechanisms involved in the CD8-mediated control of transcription may identify other factors with potential value in the treatment of HIV infection.

Prevention and early detection of type 2 diabetes in children and adolescents.

Type 2 ("adult-onset") diabetes in young adults and children has become increasingly common over the last 10 years, and has been described as an "emerging epidemic." The financial and societal ramifications of such a development are substantial and demand a prompt and aggressive public health response. Emphasis must be placed upon preventive behaviors and early detection, and creation of new public policy to address the related societal issues. Recommendations for prevention and screening of high-risk children and adolescents are provided.

Clinical websites are currently dangerous to health.

The Internet is becoming a ubiquitous medium, open to all. The paper explores the reasons why current health-related websites require extensive review and investment to ensure that they address the full spectrum of the audiences who may access their site. The audiences are no longer purely local or even solely those who work in the health domain. They will include everyone, from professional healthcare practitioners to members of the general public. The site web masters should also consider the range of purposes for which these disparate groups access the site. The language, content intensity and presentation should have a different style and be identified by its intended audience to avoid a range of problems including mis-interpretation, mis-targetting of content, mis-representation of source and quality. Inappropriate content and presentation could jeopardise the credibility of health sites, and thus healthcare provision, with the newly emerging audiences. Recent studies involving the evaluation of many web sites have assessed their 'fitness for purpose' as information repositories for different audiences. The criteria by which clinically related web contents are judged will vary, depending on the type of visitor to the site. Formal qualification of web content is ongoing--addressing both structured definition [1] and quality criteria [2]. Originators of web material should consider the full spectrum of the audiences who may access their site, from professional healthcare practitioners to members of the general public, and the purposes for which they access the site. The language, content intensity and presentation should have a different style and be identified by its intended audience to avoid a range of problems including mis-interpretation, mis-targetting of content, mis-representation of source and quality.

Modulation of HIV transcription by CD8(+) cells is mediated via multiple elements of the long terminal repeat.

HIV replication and LTR-mediated gene expression can be modulated by CD8(+) cells in a cell type-dependent manner. We have previously shown that supernatant fluids of activated CD8(+) cells of HIV-infected individuals suppress long terminal repeat (LTR)-mediated transcription of HIV in T cells while enhancing transcription in monocytic cells. Here, we have examined the effect of culture of T cells and monocytic cells with CD8(+) supernatant fluids, and subsequent binding of transcription factors to the HIV-1 LTR. In transfections using constructs in which NF kappa B or NFAT-1 sites were mutated, the LTR retained the ability to respond positively to culture with CD8 supernatant fluid in monocytic cells. Nuclear extracts prepared from both Jurkat T cells and U38 monocytic cells cultured with CD8(+) cell supernatant fluid demonstrated increased binding to the HIV-1 LTR at an AP-1 site which overlapped the chicken ovalbumin upstream promoter (COUP) site. In monocytic cells, increased binding activity was observed at the NF kappa B sites of the LTR. In contrast, an inhibition in binding at the NF kappa B sites was observed in Jurkat cells. Examination of two NFAT-1 sites revealed enhanced binding at - 260 to - 275 bp in U38 cells which was reduced by cellular activation. PMA and ionomycin-induced binding at a second NFAT-1 site (- 205 to - 216 bp) was abrogated by CD8(+) cell supernatant fluid in T cells. These results, taken together, suggest that factors present in CD8(+) supernatant fluids may act through several sites of the LTR to modulate transcription in a cell type-dependent manner.

CD8+ T cell suppressor factors and the control of infection, replication and transcription of human immunodeficiency virus.

CD8+ T cells have been shown to produce factors which modulate HIV-1 replication in both T cells and monocytic cells. Examination of the literature reveals that this modulation may occur by the production of beta-chemokines which block viral entry. However, another CD8+ T cell-derived factor(s) targets the replication of HIV-1 at the level of transcription. CD8+ T cell factors strongly suppress replication at the level of transcription in T cells and T cell lines, the factors enhance both replication and transcription in cells of the monocyte/macrophage lineage. The enhancement of transcription and replication, which is pertussis toxin sensitive is induced by increased production of TNF-alpha by the target cells. Thus, CD8+ T cells produce factors which mediate effects on transcription and replication of HIV-1 in a cell type-dependent manner. In this review a summary of the effects of chemokines and CD8-derived factors on HIV-1 transcription and replication is presented focusing on the cellular pathways which may mediate their effects on HIV transcription and replication in different cell types. The virus-host cell interactions that participate in the persistent replication of HIV in macrophages and the suppression of these functions in T cells require definition. The identification of CD8+ T cell factors which exert these controls on HIV-1 may lead to promising new therapies for HIV infection.

Effect of low-dose estrogen on hemodynamic response to stress.

OBJECTIVE: To determine the effect of low-dose esterified estrogen on hemodynamic responses at rest and during stress in postmenopausal women, and to compare the changes with those seen with conjugated equine estrogen. DESIGN: Open-label study of esterified estrogen compared with a double-blind, placebo-controlled investigation of conjugated equine estrogen. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Postmenopausal women with normal endometrium, not currently using hormones. INTERVENTION(S): Cardiovascular parameters at rest and in response to stressors were assessed in 11 postmenopausal women before and 6 months after receiving 0.3 mg esterified estrogen. Responses were compared with 42 postmenopausal women randomized to 0.625 mg conjugated equine estrogen or placebo. MAIN OUTCOME MEASURE(S): Changes in mean arterial pressure (MAP) and vascular resistance index from before to after treatment. RESULT(S): At rest, MAP increased 3.3 +/- 1.5 mm Hg (+/-SD) in the placebo group, while declining 2.3 +/- 1.5 mm Hg and 4.8 +/- 1.4 mm Hg, respectively, in the esterified estrogen and conjugated equine estrogen groups after treatment. During mental stressors, MAP dropped significantly in both treatment groups. At rest and during mental stressors, vascular resistance index decreased with estrogen treatment. CONCLUSION(S): Low-dose esterified estrogen improved hemodynamic patterns similar to standard doses of conjugated equine estrogen in postmenopausal women.

The impact of variable tint optics (Transitions Gray) on vision-related quality of life in normal volunteers: a randomized clinical comparison in a warm climate.

PURPOSE: A randomized crossover comparison of Transitions Gray variable tint optics (VTO) vs clear and fixed-tint lenses was undertaken to evaluate the impact of VTO on vision-related quality of life (VRQOL) in a warm climate. METHODS: Fifty-nine patients were randomized to one of four lens crossover groups: Transitions-->clear; clear-->Transitions; Transitions-->fixed-tint; fixed-tint-->Transitions. Each lens was worn for 30 days. VRQOL was measured using a newly developed and validated questionnaire instrument-the Transitions VRQOL. Changes in visual acuity were assessed by functional exam. RESULTS: Overall, Transitions was associated with the greatest improvement in VRQOL relative to clear and fixed-tint lenses without compromise in acuity. Transitions proved statistically superior to clear lenses, most notably in vision comfort both indoors and outdoors. Seventy percent of all patients selected Transitions as their primary lens at the end of the study. CONCLUSIONS: Transitions brand VTO offer patients significant and clinically meaningful improvements in VRQOL superior to clear lenses. VRQOL assessments provide clinicians with valuable information above and beyond visual acuity to help optimize lens product selection and enhance patient satisfaction.

Radiation exposure during air travel: guidance provided by the Federal Aviation Administration for air carrier crews.

Air carrier crews are occupationally exposed to ionizing radiation, principally from galactic cosmic radiation. To promote radiation safety in aviation the Federal Aviation Administration has: issued educational material on the nature of the radiation received during air travel; recommended radiation exposure limits for pregnant and nonpregnant aircrew members; developed computer programs that estimate for a given flight profile the amount of galactic radiation received on a current flight or on one flown at any time back to January 1958; published tables that enable aircrew members to estimate possible health risks associated with their occupational exposure to radiation; and conducted research on effects of radiation during pregnancy. References for this material are given in the article. In addition, graphic and tabular data in the article show how galactic radiation levels and the composition of the galactic radiation has changed between 1958 and 1999. Also given are estimates of effective doses received by air travelers on a wide variety of air carrier flights.

Insulin-like growth factor binding proteins (IGFBPs) in serum and urine and IGFBP-2 protease activity in patients with insulin-dependent diabetes mellitus.

Diabetes mellitus and glucose dysregulation have significant effects on the circulating level of insulin-like growth factor-I (IGF-I) and IGF binding proteins (IGFBPs). In the present study, serum and urine IGFBP (IGFBP-1, -2, and -3) and serum IGF-I and -II levels were measured by radioimmunoassay (RIA) in 27 patients with type 1 diabetes aged 9 to 48 years compared with 9 healthy subjects aged 10 to 28 years. The patients were divided into 3 groups according to the amount of albumin excreted in 24 hours. The macroalbuminuria group (>500 mg/24 h) had elevated serum IGFBP-1 and -2 and decreased IGF-I levels (P < .01 v normal controls). Serum IGFBP-3 and IGF-II were not different among the patient groups and controls (P > .05). The mean urinary IGFBP-1 was decreased in all 3 patient groups compared with the controls (P < .05). Urinary IGFBP-2 and IGFBP-3 were increased in patients with macroalbuminuria. Immunoblot analysis showed increased low-molecular-weight fragments of urinary IGFBP-2 in the poorly controlled diabetics, and direct evidence for increased urinary IGFBP-2 proteolytic activity could be demonstrated in both the microalbuminuric and macroalbuminuric groups. Low-molecular-weight fragments of urinary IGFBP-3 were also increased in both the microalbuminuric and macroalbuminuric groups. In conclusion, alterations of IGFBPs in urine and serum are related to metabolic control in diabetic patients, and there is an increase of urinary IGFBP-2 protease activity in poorly controlled diabetics. The changes in serum IGFBP concentrations (eg, increases in IGFBP-1 and IGFBP-2) may lead to alterations in the availability of IGF-I to peripheral tissues.