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Development of the gubernaculum and processus vaginalis in freemartinism: further evidence in support of a specific fetal testis hormone governing male-specific gubernacular development.

BACKGROUND: Freemartinism occurs in some species of ruminants and affects most female bovine fetuses in heterosexual, multiple pregnancies owing to fusion of the chorionic blood circulations soon after implantation. Maldevelopment of the ovaries and Müllerian ducts have been described and recognized as resulting from exposure of their respective primordia to an excess of anti-Müllerian hormone. The present study aimed to analyse the prenatal growth and development of the gubernaculum in freemartins to find out its possible affliction through foetal testis hormones derived from their male co-twin. METHODS: Histological sections of young and drawings and photographs of further developed freemartins and control male and female bovine foetuses were analysed. The specimens had been collected earlier for analysis of the time course of male and female gonadal and genital development and its impairment associated with freemartinism. RESULTS: The gubernaculum of 35-40-day-old male and female fetuses was in the initial stage of development and of similar appearance in all specimens. Gubernacula of 60-70-day-old male fetuses differed from those of females of similar age in various respects: the male gubernaculum size was larger and extension of the processus vaginalis was deeper. Freemartins showed an intermediate development with some individuals resembling male and others resembling female agemates. During further development, gubernacula in males developed into muscular cremaster sacs, whereas those in females generally did not develop beyond the size and structural complexity of 70-day-old foetuses. Beyond day 70 of fetal life, gubernaculum development in freemartins definitely showed male characteristics with respect to size and growth of a processus vaginalis with a cremaster muscular wall. The male-like pattern of the outgrowth of the processus vaginalis changed during the second half of prenatal life. Rather than its further deepening as in males, this structure became inverted to become emerging as a papilla-like structure from the inguinal abdomen bottom. An explanation is proposed for this unprecedented inversion, taking into account: (1) the faster and higher reaching rightsided ascent of the kidneys and gonads, (2) the femalelike outgrowth of the cranial gonadal suspensory ligaments, and (3) the absence of scrotum development. The ovaries and mesonephric remnants in developing freemartins, during their ascent together with the kidneys while remaining attached to the bottom of the developing processus vaginalis sacs via the gubernaculum ligament, are proposed to act together to pull up the bottom of the processus vaginalis sacs. From this action, "inverted hernia sacs" result as the irreversible consequence. CONCLUSION: The data support the concept that foetal testes act, via as an yet unidentified third hormone, to establish malelike development of gubernacula into muscular cremaster sacs. Further work is required to reveal the identity of this hormone. Furthermore, the apparent similarity of the freemartins' inverted processus vaginalis sacs and the fetal rodents' gubernacular cones suggests that the ruminants' and rodents' processus vaginalis are essentially similar structures. Thus there is no longer an urgent need to distinguish between two different types of gubernaculum development and testis descent in rodents and ruminants, respectively, and involving or not fetal gubernacular cones. The present observations may thus contribute to the development of a unified hypothesis for sexually dimorphic development of the gubernaculum throughout the mammalian class.

Androgens↗

[Comparative analysis of mortality due to violence in developed countries and in a few developing countries during the 1985-1989 period].

A comparative analysis of crude death rates and specifically of deaths from violence was conducted for a large number of developed and developing countries which provide data to the World Health Organization's data bank. For these countries, the analysis shows, first of all, that violent deaths rank third among the major causes of death, after diseases of the circulatory system and malignant tumours, in most developed countries and in some developing countries with reliable data. The comparative analysis also reveals substantial variations in the level and structure of death rates, both among the developed and the developing countries. Thus the crude death rate varies by a factor of 2 in both sexes, both in the developed and the developing countries. For violent deaths, the ranges are even wide: the highest death rate is 3 to 4 times greater than the lowest, except for women in developing countries where it is only twice as high. The method reveals in which countries the situation regarding violent deaths is relatively tolerable and in which countries the situation is decidedly bad. Although it is difficult to draw up a clear classification whereby countries can be grouped according to their profile of deaths by cause, it can be seen that a number of countries have a fairly characteristic profile of mortality by cause; these are mainly the developed countries (Western Europe and other regions) and some developing countries (Hong Kong and Israel) with low crude death rates. In these countries certain causes of violent death predominate as a result of the level of development achieved; motor vehicle accidents, falls and suicides. Moreover, in the other developed countries (in Eastern Europe) and in the developing countries (except Hong Kong and Israel) there is a more "traditional" profile of mortality by cause; this profile is characteristic of the less-developed countries where there are generally fewer deaths from suicide and from motor-vehicle accidents and where unintentional factors predominate over intentional factors. This analysis also brings out the very distinctive situation of the countries of Latin America with regard to violent deaths, particularly the large number of deaths from homicide in a number of countries. This is unquestionably a high-risk region for which further studies need to be undertaken, and where preventive measures need to be applied in order to curb the rising tide of violence and its harmful consequences for these societies.(ABSTRACT TRUNCATED AT 400 WORDS)

Accidents↗

Developing drugs for the developing world: an economic, legal, moral, and political dilemma.

This paper discusses the economic, legal, moral, and political difficulties in developing drugs for the developing world. It argues that large, global pharmaceutical companies have social responsibilities to the developing world, and that they may exercise these responsibilities by investing in research and development related to diseases that affect developing nations, offering discounts on drug prices, and initiating drug giveaways. However, these social responsibilities are not absolute requirements and may be balanced against other obligations and commitments in light of economic, social, legal, political, and other conditions. How a company decides to exercise its social responsibilities to the developing world depends on (1) the prospects for a reasonable profit and (2) the prospects for a productive business environment. Developing nations can either help or hinder the pharmaceutical industry's efforts to exercise social responsibility through various policies and practices. To insure that companies can make a reasonable profit, developing nations should honor pharmaceutical product patents and adhere to international intellectual property treaties, such as the Trade-Related Aspects of Intellectual Property Rights (TRIPS) agreement. To insure the companies have a good business environment, developing nations should try to promote the rule of law, ethical business practices, stable currencies, reliable banking systems, free and open markets, democracy, and other conditions conducive to business. Overall, this paper advocates for reciprocity and cooperation between pharmaceutical companies and developing nations to address the problem of developing drugs for the developing world. In pursuing this cooperative approach, developing nations may use a variety of other techniques to encourage pharmaceutical companies to act responsibly, such as subsidizing pharmaceutical research, helping to design and implement research protocols, providing a guaranteed market, and bulk buying.

Beneficence↗

Development of monoclonal gammopathy precedes the development of Epstein-Barr virus-induced posttransplant lymphoproliferative disorder.

Epstein-Barr virus (EBV)-induced posttransplant lymphoproliferative disorder (PTLD) develops in 3% to 10% of solid organ transplant recipients with a resultant mortality of up to 70%. Unfortunately, there is no current marker which identifies patients who will develop this disease. We therefore conducted a risk factor analysis of variables that might predict the development of PTLD. Specifically, since EBV may cause both PTLD and the development of monoclonal proteins (M protein), we sought to determine if the development of an M protein preceded and therefore might serve as a predictive marker of subsequent PTLD. Before and after liver transplantation, 201 patients were evaluated for the presence of urine and serum M proteins. Patients were followed to monitor the development of PTLD for a mean of 1,733 days. PTLD developed in seven patients (3.5%), three (43%) of whom died from disseminated PTLD. PTLD was classified as polymorphous in six patients and monomorphous in one patient. Fifty-seven patients (28%) developed an M protein after transplantation: five of seven patients (71%) with PTLD and 52/194 (27%) of patients without PTLD. Multivariate risk factor analysis for the development of an M protein after transplantation identified cytomegalovirus (CMV) donor seropositivity (P = 0.0002) and postoperative symptomatic CMV infection (P = 0.019) as risk factors. Whereas EBV serostatus of either the donor or recipient was not found to be a risk factor for the occurrence of either an M protein or PTLD, the development of a serum immunoglobulin M (IgM) M protein (P = 0.04) and of any urine M protein (P = 0.01) was identified by univariate analysis as being associated with the development of PTLD. Further studies are needed to determine the predictive value of M proteins as a marker for PTLD. Until such time, the development of serum or urine M protein should heighten the suspicion of developing PTLD.

Adolescent↗

Morphological development, cell number, and allocation of cells to trophectoderm and inner cell mass of in vitro fertilized and parthenogenetically developed buffalo embryos: the effect of IGF-I.

The morphology and number of cells in the trophectoderm (TE) and inner cell mass (ICM) of buffalo blastocysts derived from in vitro fertilization and cultured in the presence or absence of insulin-like growth factor-I (IGF-I) were analyzed by differential fluorochrome staining technique. The total cell number (TCN), TE number, and ICM cell number were significantly higher in blastocysts developed in vitro in the presence of IGF-I as compared to blastocysts developed without IGF-I (P < 0.01). It was observed that the buffalo blastocyst took 5-9 days postfertilization to develop in vitro. In order to correlate the time required for blastocyst development and the allocation of cells to TE and ICM, blastocysts were designated as fast (developing on or before day 7) or slow (developing after day 7). The TCN, TE, and ICM cells of fast-developing blastocysts cultured in the presence of IGF-I were significantly higher than slow-developing blastocysts (P < 0.01). The blastocysts developed on day 6 had a mean total cell number 118.6 +/- 21.4, which significantly decreased to 85.6 +/- 17.4, 62.0 +/- 14.5, and 17.0 +/- 4.0 on days 7, 8, and 9, respectively (P < 0.05). Normal development of buffalo embryo showed that, on average, embryos reached compact morula stage at the earliest between days 4.5-5.5. Blastocysts developed, at the earliest, between days 5.0-6.0, and it took them, on average, 6.5 days to hatch from the zona pellucida. TCN, TE, and ICM increased three times from morula to blastocyst; however, the proportion of ICM to TCN remained the same, in both embryonic stages. TE approximately doubled in hatched blastocysts, as compared to unhatched blastocysts (P < 0.05). However, ICM cells were decreased. The time required for development of parthenogenetic blastocysts was observed to be greater as compared to in vitro fertilized (IVF) blastocysts. The total cell number of parthenogenetic blastocysts was 100.8 +/- 11.3, including 59.2 +/- 8.4 cells of TE and 42.1 +/- 6.9 cells of ICM.

Animals↗

The practice guidelines development cycle: a conceptual tool for practice guidelines development and implementation.

PURPOSE: To develop a conceptual tool for the systematic development of cancer treatment practice guidelines. MATERIALS AND METHODS: The guidelines development tool, the Practice Guidelines Development Cycle, was derived from observing an evidence-based practice guidelines initiative at a comprehensive cancer center in Ontario, Canada, and from a literature review that uncovered barriers to guidelines development and implementation. Based on the literature findings and direct observations of how clinicians struggled with evidence-based guidelines development, we evolved a framework to incorporate clinical and administrative factors (eg, costs) into evidence-based guidelines. Use of the Practice Guidelines Development Cycle is illustrated with a clinical example (the use of adjuvant systemic therapy in good-risk, node-negative premenopausal breast cancer patients). RESULTS: The result is the Practice Guidelines Development Cycle, which consists of eight sequential steps, from topic selection to policy formulation. Independent validation of guidelines is included. The cycle products are the evidence-based recommendation, the practice guideline, and the practice policy. The main features of the cycle are emphasis on scientific evidence, acknowledgment of the roles of clinical experience and nonclinical (administrative) factors through consensus, and explicit separation of clinical and cost considerations in guidelines development. Twenty guidelines are currently in development. CONCLUSION: Attention to the barriers of guidelines development and the sociocultural nature of clinical practice, and respect for clinical experience, can lead to improved strategies for guidelines development.

Cancer Care Facilities↗

The development of nurses as managers: the prevalence of the self-development route.

AIM: This article identifies ways in which hospital sisters and charge nurses (ward managers) are developed as managers in one London teaching hospital. CONTEXT: Ward managers are practising in the context of increasing management responsibility in which decision-making is being driven to occur as close to the patient as possible. Decision-making about the management development opportunities for ward managers rests with senior nurse managers who have espoused their own preferences about the styles of management development open to ward managers. METHODS: For this small-scale exploratory-descriptive study, qualitative research methods were used with a postal self-completed questionnaire followed by a focus group. The target population was a group of 22 senior nurse managers. There was a questionnaire response rate of 68% (n = 15 respondents, four of whom participated in the focus group). FINDINGS: The research exposed and substantiated four styles of management development. The organizational prevalence of these styles and the ward managers' preference for each style were also ascertained. The most prevalent style was the one for which there was the least preference. CONCLUSIONS: The findings indicated that there was a general mismatch between the style of management development prevalent in the organization and the style of management development preferred by the subjects. This left the ward managers generally to follow an unstructured self-development route. The use of a theoretical framework, expressed as a Reluctance-Readiness to Manage Continuum, is suggested to harness the propensity to self-develop and to link it with the organizational need to develop nurses as managers through the paradox of structuring self-development.

Attitude of Health Personnel↗

A Digital Tool for Clinical Evidence-Driven Guideline Development by Studying Properties of Trial Eligible and Ineligible Populations: Development and Usability Study.

BACKGROUND: Clinical guideline development preferentially relies on evidence from randomized controlled trials (RCTs). RCTs are gold-standard methods to evaluate the efficacy of treatments with the highest internal validity but limited external validity, in the sense that their findings may not always be applicable to or generalizable to clinical populations or population characteristics. The external validity of RCTs for the clinical population is constrained by the lack of tailored epidemiological data analysis designed for this purpose due to data governance, consistency of disease or condition definitions, and reduplicated effort in analysis code. OBJECTIVE: This study aims to develop a digital tool that characterizes the overall population and differences between clinical trial eligible and ineligible populations from the clinical populations of a disease or condition regarding demography (eg, age, gender, ethnicity), comorbidity, coprescription, hospitalization, and mortality. Currently, the process is complex, onerous, and time-consuming, whereas a real-time tool may be used to rapidly inform a guideline developer's judgment about the applicability of evidence. METHODS: The National Institute for Health and Care Excellence-particularly the gout guideline development group-and the Scottish Intercollegiate Guidelines Network guideline developers were consulted to gather their requirements and evidential data needs when developing guidelines. An R Shiny (R Foundation for Statistical Computing) tool was designed and developed using electronic primary health care data linked with hospitalization and mortality data built upon an optimized data architecture. Disclosure control mechanisms were built into the tool to ensure data confidentiality. The tool was deployed within a Trusted Research Environment, allowing only trusted preapproved researchers to conduct analysis. RESULTS: The tool supports 128 chronic health conditions as index conditions and 161 conditions as comorbidities (33 in addition to the 128 index conditions). It enables 2 types of analyses via the graphic interface: overall population and stratified by user-defined eligibility criteria. The analyses produce an overview of statistical tables (eg, age, gender) of the index condition population and, within the overview groupings, produce details on, for example, electronic frailty index, comorbidities, and coprescriptions. The disclosure control mechanism is integral to the tool, limiting tabular counts to meet local governance needs. An exemplary result for gout as an index condition is presented to demonstrate the tool's functionality. Guideline developers from the National Institute for Health and Care Excellence and the Scottish Intercollegiate Guidelines Network provided positive feedback on the tool. CONCLUSIONS: The tool is a proof-of-concept, and the user feedback has demonstrated that this is a step toward computer-interpretable guideline development. Using the digital tool can potentially improve evidence-driven guideline development through the availability of real-world data in real time.

Humans↗

Thyroid development in relation to the development of endothermy in the red-winged blackbird (Agelaius phoeniceus).

We investigated the development of thyroid function during the transition to endothermy in red-winged blackbirds (Agelaius phoeniceus). Thermoregulatory capabilities of blackbirds improve markedly over their relatively short nestling period (10-12 days), with the most striking improvements occurring between days 6 and 8. We hypothesized that the development of endothermy in these birds is dependent in part on the development of thyroid function. We assessed thyroid development by measuring changes in thyroid gland histology and plasma concentrations of thyroxine (T4) and triiodothyronine (T3) during the nestling period. To gain insight into the role of thyroid maturation in the context of thermoregulation, we compared plasma thyroid hormone profiles in nestlings exposed to cold temperatures to those maintained at thermoneutral temperatures. The overall size of the thyroid (as cross-sectional area) increased during nestling development, with the fastest growth occurring just before the development of endothermy. By day 8, it reached the size typical of that in adults. Follicular cell height of the thyroid glands increased in nestlings up to day 6 and then decreased for the rest of the nestling period. The mean area of individual follicles increased up to day 8 of nestling life and then decreased. Individual nestlings were capable of strong endothermic responses at 7 to 8 days of age and had significantly decreased plasma T4 concentrations following cold exposure, suggesting increased T4 to T3 deiodination to maintain the plasma concentrations of the more metabolically active T3. The patterns of plasma T4 and T3 during nestling development were consistent with those of nestlings of other altricial species of birds that have been studied. Overall, the patterns of thyroid development observed were consistent with the hypothesis that the functional development of the thyroid is critical to the development of endothermic capabilities and that thyroid hormones play a role in endothermic responses to cold temperatures.

Animals↗

The development of catecholaminergic nerves in the spinal cord of rat. II. Regional development.

The development of noradrenergic and dopaminergic nerves in 5 regions of the developing spinal cord of rat, from fetal day (FD) 16, to the young adult stage was studied. The normal synthetic capacity of adrenergic nerves in the ventral horn of the cervical and lumbar regions developed at the same time, and at the same rate, despite their spatial separation, and before similar development of the noradrenergic nerves in the dorsal horn and zona intermedia. In the ventral horn, the synthesis of NE from injected L-DOPA, as well as the release and metabolism of NE are well-established at 12 h (ND 0.5) after birth. In the dorsal horn these developments occur later at ND 4. Except in the dorsal horn of the cervical region, there was no easily observable, consistent pattern in the development of regional spinal dopaminergic innervation. The capacity of the developing cord to synthesize dopamine (DA) from injected DOPA is significantly developed at FD 16 (the earliest time studied), and peaked in all regions as early as ND 4. Control experiments indicate that 100%, and only 10% respectively of NE and DA synthetized from injected DOPA, occurred in descending monoaminergic fibers. Norepinephrine is synthesized exclusively in noradrenergic nerves. Cells appear transiently in the developing cord at FD 18, that are capable of synthesizing catecholamines (probably mainly DA) from injected DOPA. During postnatal development of the cord, and to a less extent in the adult, the network of catecholaminergic nerves actually present, is more extensive than that normally revealed during routine fluorescence microscopy. The results are discussed in the context of current attempts to understand the functional importance of catecholaminergic nerves in the mammalian spinal cord, and elsewhere in the CNS.

Aging↗

General types of relationships between the development of the organism and the development of the subsystems of the organism.

There are elementary and complex types (combined elementary types): of temporospatial relations between the pattern of development of the organism and the patterns of development of individual subsystems; of influences exercised by the development of the organism upon the development of the subsystems of the organism; of influences exercised by the development of individual subsystems upon individual development; of temporospatial relations between the stability of the line of individual development and the stability of the line of development of individual subsystems; of mutual influence between the stability and variation of the line of individual development, on the one hand, and the stability and variation of the line of development of the individual subsystems, on the other.

Environment↗

Research on informed consent: investigator-developed versus focus group-developed consent documents, a VA cooperative study.

In the Department of Veterans Affairs Cooperative Study (VACSP) #470, A Randomized, Multicenter, Controlled Trial of Multi-Modal Therapy in Veterans with Gulf War Illnesses, a substudy was designed with the primary objective of comparing the utility of an informed consent document developed by a focus group of Gulf War veterans (focus group-developed) to an informed consent document developed by the standard process involving the study investigators (investigator-developed). In December 1998 a focus group of five Gulf War veterans convened at the coordinating center and developed a consent document during three sessions. The focus group used the investigator-developed consent document as a "starting point" and then modified it by consensus agreement. They also reviewed and modified the substudy's assessment questionnaire. Utility will be evaluated in 1092 veterans participating in the parent study, VACSP #470, by directly comparing selected patient-centered outcomes between those receiving the focus group-developed consent document versus those receiving the investigator-developed document. The primary outcomes to be evaluated over a 1-year follow-up period include measures of the informed consent process, such as patient recall, expectations about risks and benefits of participation, and understanding about the voluntariness of consent. Secondary outcomes will assess the impact of the substudy on the parent study with respect to recruitment and adherence. VACSP #470 was initiated in May 1999 in 20 sites that were randomly allocated to use either the focus group-developed or investigator-developed consent document. Sites are unaware of the type of consent document assigned. This article focuses on the rationale and design of the informed consent substudy and also discusses potential ethical issues.

Focus Groups↗

What can developing economies learn from health system reforms of developed countries?

This paper outlines some general lessons developing nations can draw from the health system reform experiences of developed nations. Using the experiences of developed countries, developing countries should be better able to anticipate socio-economic changes and choose an optimal path for their health systems development to accompany those changes. Most developed countries have adopted rather common objectives and principles in their health systems because of market failure in health care; developing countries may start adopting those principles because they do not have market conditions in the first place. It is suggested that developing countries strengthen what is probably the most fundamental initial systemic asset they have: public finance. They should do so by attracting democratically, possibly through earmarked taxes, resources otherwise channelled through the private sector, competing with public finance for limited real resources. This effort can be promoted by giving consumers, mainly of high income groups and in urban areas, more say (through institutions performing the OMCC function) in the nature of care these groups have access to under auspices of public finance. Where feasible, private insurance as a major source of finance should be seen as a transitional phenomenon, giving way to the emergence of OMCC institutions which require similar financial and managerial market infrastructure. Private and competitive provision of care may be unrealistic in many developing areas because of both scarcity of real resources, mainly manpower, and health needs. The challenge of government is, as resources grow, to divest itself from the provision of care and stay involved in activities and facilities that are of 'public nature'--under specific circumstances--that foster private competitive provision. In general, the government should play an enabling role also by investing in health promotions and management skills for health systems.

Developed Countries↗

Post-hatching development of the porcine and bovine embryo--defining criteria for expected development in vivo and in vitro.

Particular attention has been paid to the pre-hatching period of embryonic development although blastocyst development is a poor indicator of embryo viability. Post-hatching embryonic development in vitro would allow for establishment of more accurate tools for evaluating developmental potential without the need for transfer to recipient animals. Such a system would require (1) definition of milestones of expected post-hatching embryonic development in vivo; and (2) development of adequate culture systems. We propose a stereomicroscopical staging system for post-hatching embryos defining the following stages: (1) Expanded hatched blastocyst stage where the embryo presents an inner cell mass (ICM) covered by trophoblast. (2) Pre-streak stage 1 where the embryonic disc is formed. (3) Pre-streak stage 2 where a crescent-shaped thickening of the caudal portion of the embryonic disk appears. (4) Primitive streak stage where the primitive streak has developed as an axis of cell ingression of cells for meso- and endoderm formation. (5) Neural groove stage where the neural groove is developing from the rostral pole of the embryo along with a proportional shortening of the primitive streak; and (6) Somite stage(s) where paraxial mesoderm gradually condensates to form somites. Post-hatching development of bovine embryos in vitro is compromised and although hatching occurs and elongation can be physically provoked by culture in agarose tunnels, the embryonic disk characterizing the pre-streak stage 1 is never established. Thus, particular focus should be placed on establishing culture conditions that support at least some of the above-mentioned critical phases of development that in vivo occur within the initial two (pig) to three (cattle) weeks.

Animals↗

Relationship between gestures and words in children with Down's syndrome and typically developing children in the early stages of communicative development.

BACKGROUND: Previous research has emphasized the importance of gesture in early communicative development. These studies have reported that gestures are used frequently during the first two years of life and may play a transitional role in the language acquisition process. Although there are now numerous descriptions of the relationship between gesture and the developing language system in typically-developing (TD) children, relatively little is known about the nature and early development of the gesture-language system in children with developmental disorders involving specific profiles of language delay and/or impairment. PRIMARY OBJECTIVE: The aim of this study is to compare early word and gesture use in children with DS and in typically-developing children to investigate potential differences in the relationship between gestural and verbal communication in early language development. METHODS AND PROCEDURES: Ten children from upper-middle class families participated in the study. The five children with DS (3 boys and 2 girls) had an average chronological age of 47.6 months, an average mental age of 22.4 months, and an average language age of 18 months. Each child with DS was matched to a typically developing child on the basis of gender, language age, and observed expressive vocabulary size. Children were videotaped for 30 minutes as they interacted spontaneously with their mothers. All communicative and intelligible gestures and words produced by the children were transcribed from the videotapes. Data analyses focused on: a) overall production of gestures and words (i.e., gesture and word tokens); b) the size of children's gestural and verbal repertoires (i.e., gesture and word types); and c) production and informational content of gesture-word combinations. MAIN OUTCOMES AND RESULTS: Although children with DS had significantly smaller gestural repertoires than their language age-matched peers, there was no reliable difference between the two groups in the overall use of gesture. In addition, with DS produced two-element combinations (primarily gesture-word combinations) and did so at a rate comparable to that observed among their TD counterparts. However, no two-word combinations were observed among children with DS, and there were also group differences in the information contained in children's gesture-word combinations. CONCLUSIONS: Taken together, these findings suggest that in addition to the well-documented global delays in early communicative development, children with DS may exhibit additional pockets of delay, specifically in making the transition from one- to two-word speech. Results are further discussed in terms of their implications for understanding the organization of the developing gesture-language system and for the assessment of gesture in young children with communicative delays and disorders.

Child, Preschool↗